Cadmium Poisoning

Environmental MONDO:0043523 Pathograph 22 heavy metal poisoning

Cadmium poisoning is a toxic condition resulting from acute or chronic exposure to cadmium, a heavy metal encountered primarily through occupational sources (silver jewelry industry, zinc smelting, battery manufacturing), contaminated food and water, and tobacco smoke. Acute inhalation of cadmium fumes causes severe pneumonitis and acute lung injury. Chronic exposure leads to progressive renal tubular dysfunction (Fanconi syndrome), hypophosphataemic osteomalacia, osteoporosis, and peripheral neuropathy. The most severe form of chronic cadmium toxicity is itai-itai disease, endemic in cadmium-polluted regions of Japan, characterized by severe bone pain, fractures, and renal failure. Cadmium has a long biological half-life (10-30 years) and there is no effective antidote; management centers on exposure cessation, chelation therapy, and supportive care.

Ask OpenScientist

Ask a research question about Cadmium Poisoning. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).

Submitting...

Do not include personal health information in your question. Questions and results are cached in your browser's local storage.

14
Pathophys.
5
Histopath.
9
Phenotypes
22
Pathograph
5
Medical Actions
2
Subtypes
5
Differentials
1
Datasets
4
Trials
9
References
1
Deep Research
◆

Subtypes

2
Acute Cadmium Poisoning (Inhalation)
Acute cadmium poisoning from inhalation of cadmium fumes or dust, typically occurring in occupational settings (welding, smelting, silver jewelry manufacturing). Presents with acute lung injury, chemical pneumonitis, pulmonary edema, and potentially fatal respiratory failure. Symptoms may be delayed 12-36 hours after exposure.
Show evidence (2 references)
PMID:16933734 SUPPORT Human Clinical
"Heavy metal inhalation is a rare cause of acute lung injury. Among the various heavy metals, cadmium is more commonly known to cause acute lung injury."
Confirms acute cadmium inhalation as a cause of acute lung injury.
PMID:41000307 SUPPORT Human Clinical
"For patients with concurrent lung and kidney involvement, mechanical ventilation and continuous renal replacement therapy (CRRT) may be required."
Systematic review confirms severe acute presentations requiring ventilatory support.
Chronic Cadmium Poisoning (Itai-itai Disease)
Chronic cadmium toxicity from prolonged low-level exposure via contaminated food, water, or occupational sources. Characterized by progressive renal tubular dysfunction, Fanconi syndrome, hypophosphataemic osteomalacia, osteoporosis, and pathologic fractures. Itai-itai disease represents the most severe form, endemic in cadmium-polluted areas of Japan.
Show evidence (2 references)
PMID:39111871 SUPPORT Human Clinical
"Itai-itai disease is the most severe case of chronic cadmium (Cd) toxicity, which was endemic in Cd-polluted areas in the Jinzu River basin in Toyama prefecture, Japan."
Describes itai-itai disease as the most severe form of chronic cadmium toxicity.
PMID:23800513 SUPPORT Human Clinical
"He was finally diagnosed with chronic cadmium toxicity resulting from long-term occupational exposure."
Case report confirming chronic cadmium toxicity from occupational exposure with renal and skeletal manifestations.
⚙

Pathophysiology

14
Cadmium Absorption and Systemic Distribution
Cadmium enters the body via inhalation of fumes/dust or gastrointestinal absorption from contaminated food and water. Inhaled cadmium has 25-50% bioavailability; oral absorption is lower (3-8%) but enhanced by iron deficiency via shared divalent metal transporter 1 (DMT1). Once absorbed, cadmium distributes via the bloodstream bound to albumin and accumulates in liver, kidney, and bone with a biological half-life of 10-30 years.
cellular response to cadmium ion GO:0071276
Downstream
Hepatic Metallothionein Binding Absorbed cadmium is transported to the liver for initial processing
NF-kB/MAPK Inflammatory Signaling Cadmium ions directly activate inflammatory signaling cascades
Direct Osteoblast Toxicity Circulating cadmium has direct toxic effects on bone cells
Hepatic Glutathione Depletion Cadmium causes oxidative stress in hepatocytes
Cadmium-Induced Vascular Cholesterol Dysregulation Circulating cadmium disrupts vascular cholesterol homeostasis via miRNA modulation
Show evidence (5 references)
PMID:23800513 SUPPORT Human Clinical
"Cadmium has a long biological half-life and there is no effective treatment for people who are exposed to it."
Confirms cadmium's long biological half-life contributing to progressive systemic accumulation.
PMID:22349354 SUPPORT Human Clinical
"In both cases, multiple organ damage was observed, involving brain, lung, liver, kidney, red blood cells, and platelets"
Autopsy findings confirm systemic cadmium distribution to multiple organs.
PMID:41000307 SUPPORT Human Clinical
"The study also found that low iron stores exacerbate cadmium poisoning."
Confirms that iron deficiency enhances cadmium absorption via shared transport mechanisms.
+ 2 more references
Hepatic Metallothionein Binding
The liver is the primary site of initial cadmium detoxification. Hepatocytes synthesize metallothionein (MT), a cysteine-rich protein that binds cadmium with high affinity. The cadmium-metallothionein (Cd-MT) complex is slowly released into the bloodstream over time. While MT binding initially protects against free cadmium toxicity, the Cd-MT complex is filtered at the glomerulus and taken up by renal tubular cells, effectively transferring the cadmium burden to the kidney.
hepatocyte CL:0000182
detoxification of inorganic compound GO:0061687
liver UBERON:0002107
Downstream
Renal Proximal Tubular Cadmium Uptake Cd-MT complex released from liver is filtered by glomerulus and reabsorbed by proximal tubule
Show evidence (2 references)
PMID:25042840 SUPPORT Model Organism
"This half-life is partly as a result of metallothioneins (MTs), metal-binding proteins with a high affinity for Cd."
Confirms metallothionein as the primary cadmium-binding protein responsible for cadmium's long biological half-life.
PMID:20354761 SUPPORT Human Clinical
"The kidney is the main organ affected by chronic Cd exposure and toxicity. Cd accumulates in the kidney as a result of its preferential uptake by receptor-mediated endocytosis of freely filtered and metallothionein bound Cd (Cd-MT) in the renal proximal tubule."
Review confirms that hepatically-produced Cd-MT is filtered and taken up by the kidney, establishing the liver-to-kidney transfer pathway.
Renal Proximal Tubular Cadmium Uptake
The cadmium-metallothionein (Cd-MT) complex is freely filtered at the glomerulus due to its small molecular weight (~7 kDa). Proximal tubular epithelial cells reabsorb Cd-MT via receptor-mediated endocytosis through the megalin/cubilin receptor complex. Once internalized, Cd-MT is degraded in lysosomes, releasing free cadmium ions intracellularly. This mechanism explains the kidney's particular vulnerability to cadmium accumulation.
proximal tubule cell CL:0002306
receptor-mediated endocytosis GO:0006898
proximal tubule UBERON:0004134
Downstream
Proximal Tubular Cell Injury Accumulated free cadmium exceeds intracellular metallothionein binding capacity
Show evidence (4 references)
PMID:20204475 SUPPORT Human Clinical
"the multiligand endocytic receptors megalin and cubilin take up cadmium-metallothionein complexes via receptor-mediated endocytosis."
Demonstrates that megalin and cubilin receptors mediate the endocytic uptake of Cd-MT complexes in proximal tubule.
PMID:34298880 SUPPORT Model Organism
"Cd2+ complexed to metallothionein (MT) (CdMT) is taken up through receptor-mediated endocytosis (RME) via the PT receptor megalin:cubilin, which is the predominant pathway for reuptake of filtered proteins in the kidney."
Confirms megalin:cubilin as the predominant receptor for Cd-MT uptake in proximal tubule.
PMID:20354761 SUPPORT Human Clinical
"Cd accumulates in the kidney as a result of its preferential uptake by receptor-mediated endocytosis of freely filtered and metallothionein bound Cd (Cd-MT) in the renal proximal tubule. Internalised Cd-MT is degraded in endosomes and lysosomes, releasing free Cd(2+) into the cytosol"
Review details the full Cd-MT uptake pathway: glomerular filtration, receptor-mediated endocytosis, lysosomal degradation, and free Cd2+ release.
+ 1 more reference
Proximal Tubular Cell Injury
When intracellular cadmium exceeds the metallothionein binding capacity of proximal tubular cells (typically at renal cortex concentrations above 200 mcg/g), free cadmium ions cause oxidative stress, mitochondrial dysfunction, and activation of apoptotic pathways. Cadmium displaces zinc from zinc-finger proteins and disrupts calcium signaling, leading to tubular cell death.
proximal tubule cell CL:0002306
apoptotic process GO:0006915 ↑ INCREASED
proximal tubule UBERON:0004134
Downstream
Impaired Tubular Reabsorption Tubular cell injury and death cause loss of reabsorptive function
Chronic Kidney Disease Progression Sustained tubular injury leads to tubulointerstitial fibrosis
Show evidence (2 references)
PMID:39111871 SUPPORT Human Clinical
"She had chronic renal failure with a high Cd exposure level and advanced renal tubular dysfunction."
Documents advanced renal tubular dysfunction resulting from proximal tubular cell injury in chronic cadmium exposure.
PMID:20354761 SUPPORT Human Clinical
"Internalised Cd-MT is degraded in endosomes and lysosomes, releasing free Cd(2+) into the cytosol, where it can generate reactive oxygen species (ROS) and activate cell death pathways."
Review details the mechanism of tubular cell injury: lysosomal release of free Cd2+ generates ROS and activates apoptosis.
Impaired Tubular Reabsorption
Injury to proximal tubular cells causes Fanconi syndrome, characterized by impaired reabsorption of low-molecular-weight proteins (beta-2- microglobulin, retinol-binding protein), glucose, amino acids, uric acid, and phosphate. This is the earliest and most sensitive clinical indicator of chronic cadmium nephrotoxicity, detectable before decline in GFR.
proximal tubule cell CL:0002306
renal tubular reabsorption GO:0070295 ↓ DECREASED
kidney UBERON:0002113
Downstream
Renal Phosphate Wasting Impaired proximal tubular phosphate reabsorption causes phosphaturia
Renal Tubular Dysfunction Loss of proximal tubular reabsorptive function manifests as Fanconi syndrome (renal tubular dysfunction).
Low-Molecular-Weight Proteinuria Impaired receptor-mediated reabsorption of low-molecular-weight proteins (beta-2-microglobulin, retinol-binding protein) produces tubular proteinuria.
Show evidence (4 references)
PMID:23800513 SUPPORT Human Clinical
"We report the case of a 48-year-old man who presented with severe osteoporosis, impaired renal function and acquired Fanconi syndrome."
Case report confirming cadmium-induced acquired Fanconi syndrome with impaired tubular reabsorption.
PMID:20576581 SUPPORT In Vitro
"Cd reduced the transcriptional expression of megalin and ClC5 and, at the same time, increased the degradation of megalin and ClC5 proteins via the lysosomal pathway in an in vitro model of renal proximal tubular cells."
Demonstrates the molecular mechanism: cadmium downregulates megalin and ClC5, the key receptors for protein reabsorption, explaining Fanconi syndrome.
PMID:32244724 SUPPORT In Vitro
"The exposure of S1 and S2 cells to Cd at 1 and 3 µM for 3 days resulted in significant decreases in the uptakes of β2-MG and metallothionein but not in those of albumin or transferrin."
In vitro study directly demonstrates cadmium impairs endocytic uptake of low-molecular-weight proteins at nonlethal concentrations.
+ 1 more reference
Renal Phosphate Wasting
Impaired proximal tubular phosphate reabsorption leads to chronic phosphaturia and hypophosphataemia. The sustained phosphate loss is the primary metabolic driver of cadmium-induced osteomalacia, as phosphate is essential for hydroxyapatite crystal formation in bone.
phosphate ion transport GO:0006817 ⚠ ABNORMAL
proximal tubule UBERON:0004134
Downstream
Hypophosphataemia Sustained renal phosphate loss lowers serum phosphate, producing hypophosphataemia.
Defective Bone Mineralization Chronic hypophosphataemia impairs hydroxyapatite deposition in bone matrix
Show evidence (1 reference)
PMID:31974582 SUPPORT Human Clinical
"Three silversmiths presented similarly with clinical, biochemical and radiological evidence of hypophosphataemic osteomalacia."
Confirms hypophosphataemia from renal phosphate wasting as the driver of cadmium-induced osteomalacia.
Chronic Kidney Disease Progression
Sustained proximal tubular injury from cadmium accumulation leads to tubulointerstitial inflammation, fibrosis, and progressive nephron loss. Glomerular filtration rate declines as tubulointerstitial nephritis advances, ultimately resulting in chronic kidney disease.
kidney UBERON:0002113
Downstream
Chronic Kidney Disease Progressive tubulointerstitial nephritis and nephron loss reduce GFR, producing chronic kidney disease.
Show evidence (2 references)
PMID:39111871 SUPPORT Human Clinical
"She had chronic renal failure with a high Cd exposure level and advanced renal tubular dysfunction."
Documents progression to chronic renal failure from sustained cadmium-induced tubular damage.
PMID:20354761 SUPPORT Human Clinical
"Continued and heavy Cd exposure can progress to the clinical renal Fanconi syndrome, and ultimately to renal failure."
Review confirms the progressive nature of cadmium nephrotoxicity from tubular dysfunction to renal failure.
Defective Bone Mineralization
Chronic hypophosphataemia from renal phosphate wasting impairs hydroxyapatite crystal deposition in osteoid, causing osteomalacia. Bone becomes soft and prone to deformation and pathologic fractures. In itai-itai disease, severe demineralization causes fractures from minimal trauma, height loss, and skeletal deformities.
bone mineralization GO:0030282 ↓ DECREASED
bone UBERON:0002481
Downstream
Osteomalacia Impaired hydroxyapatite deposition in osteoid produces osteomalacia (soft, undermineralized bone).
Bone Pain Osteomalacia and resulting pathologic fractures produce the severe bone pain characteristic of itai-itai disease.
Show evidence (2 references)
PMID:31974582 SUPPORT Human Clinical
"Three silversmiths presented similarly with clinical, biochemical and radiological evidence of hypophosphataemic osteomalacia."
Confirms defective bone mineralization causing osteomalacia in cadmium-exposed workers.
PMID:39111871 SUPPORT Human Clinical
"The shortening of height, bone deformities and fractures, abnormal bone metabolism suggesting osteomalacia, and renal anemia were also noted."
Documents skeletal consequences of defective mineralization in itai-itai disease.
Direct Osteoblast Toxicity
Cadmium directly inhibits osteoblast differentiation and function independently of the renal phosphate wasting pathway. Cadmium disrupts calcium signaling in osteoblasts, inhibits alkaline phosphatase activity, and promotes osteoclast-mediated resorption, contributing to osteoporosis even before significant renal damage develops.
osteoblast CL:0000062
osteoblast differentiation GO:0001649 ↓ DECREASED
bone UBERON:0002481
Downstream
Defective Bone Mineralization Impaired osteoblast function compounds the mineralization defect from phosphate wasting
Osteoporosis Direct osteoblast inhibition and enhanced osteoclastic resorption reduce bone mineral density, producing osteoporosis.
Show evidence (1 reference)
PMID:18072106 SUPPORT Human Clinical
"We will present a case of cadmium induced peripheral neuropathy, nephropathy, and decreased bone density."
Documents decreased bone density from cadmium exposure, consistent with direct bone cell toxicity.
Hepatic Glutathione Depletion
Cadmium depletes hepatic glutathione stores and inhibits antioxidant enzymes (SOD, GSH-Px, CAT), disrupting the cellular redox balance. Lipid peroxidation increases (elevated MDA), and the glutathione metabolic pathway is overwhelmed. Cadmium also affects drug metabolism through altered cytochrome P450 activity.
hepatocyte CL:0000182
glutathione metabolic process GO:0006749 ⚠ ABNORMAL
liver UBERON:0002107
Downstream
Hepatocyte Apoptosis Oxidative stress from glutathione depletion triggers apoptotic cell death
Show evidence (3 references)
PMID:39381600 SUPPORT Model Organism
"liver SOD, GSH-Px, T-AOC and CAT levels were decreased, and MDA level was increased in Cd-treated goats, and 630 DEPs (up 326, down 304) in the livers of Cd-treated goats."
Proteomic study in goats confirms cadmium-induced hepatic antioxidant depletion.
PMID:40164036 SUPPORT Model Organism
"exercise significantly decreased blood ALT and AST levels, alleviating oxidative stress in the liver by reducing MDA synthesis and enhancing SOD and GSH-PX activities."
Mouse model demonstrates cadmium-induced hepatic oxidative stress with depleted antioxidant enzymes.
PMID:41188353 SUPPORT Model Organism
"Cd exposure altered hepatic lipid homeostasis via the perturbation of steatosis gene expression and lipid species abundances. Additionally, Cd exposure triggered a hepatic antioxidant response"
Mouse model demonstrates cadmium triggers hepatic antioxidant response and disrupts lipid homeostasis, consistent with oxidative stress-driven liver injury.
Hepatocyte Apoptosis
Sustained oxidative stress from glutathione depletion triggers hepatocyte apoptosis via mitochondrial pathways. Cadmium causes release of pro- apoptotic proteins (cytochrome c, caspase-3, Bax) and nuclear damage, leading to progressive hepatocellular loss and liver injury.
hepatocyte CL:0000182
apoptotic process GO:0006915 ↑ INCREASED
liver UBERON:0002107
Show evidence (1 reference)
PMID:40164036 SUPPORT Model Organism
"Exercise inhibited nuclear damage and hepatocyte apoptosis caused by Cd by increasing Bcl-2 protein expression and preventing the release of pro-apoptotic proteins such as caspase-3, Cytc, Bax, caspase-8and cleaved-caspase-3."
Mouse model demonstrates cadmium-induced hepatocyte apoptosis via pro-apoptotic protein release.
NF-kB/MAPK Inflammatory Signaling
Cadmium activates pro-inflammatory signaling cascades including the NF-kB and MAPK/JNK pathways, leading to increased secretion of pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, IL-8, CCL2) and upregulation of COX-2. This chronic inflammatory state exacerbates organ-specific injury in kidney, liver, and intestine.
inflammatory response GO:0006954 ↑ INCREASED
Downstream
Proximal Tubular Cell Injury Inflammatory cytokines exacerbate tubular cell damage
Hepatic Glutathione Depletion Inflammatory mediators compound hepatic oxidative stress
Show evidence (2 references)
PMID:40191670 SUPPORT In Vitro
"the environmental pollutant cadmium is known to increase the secretion of pro-inflammatory cytokines, including interleukin (IL)-6, IL-8, and chemokine (C-C motif) ligand 2 (CCL2) by activating the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways."
In vitro study demonstrates cadmium activation of MAPK and NF-kB inflammatory pathways with cytokine secretion.
PMID:40164036 SUPPORT Model Organism
"exercise, both before and during Cd exposure, can reduce Cd caused pathological damages in the liver and duodenum of mice, suppressing the expression levels of the IL-1β, IL-6 and TNF-α genes."
Mouse model confirms cadmium-induced expression of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α.
Cadmium-Induced Vascular Cholesterol Dysregulation
Cadmium disrupts cholesterol homeostasis in the vascular wall, promoting atherosclerosis through miRNA-mediated dysregulation of cholesterol uptake (CD36), efflux (ABCA1), and hydrolysis (NCEH1). Cadmium upregulates miR-30d-5p and downregulates miR-504-3p, promoting foam cell formation and intracellular lipid accumulation in macrophages. This pathway links cadmium exposure to increased cardiovascular risk, particularly ischemic stroke.
cholesterol homeostasis GO:0042632 ⚠ ABNORMAL
Show evidence (3 references)
PMID:41297938 SUPPORT Model Organism
"Cd exposure, even at a relatively low dosage (4 mg/L), significantly facilitates the progression of atherosclerosis in apolipoprotein E-deficient mice fed a high-fat diet. This pro-atherogenic effect was accompanied by comprehensive disturbances in systemic and vascular cholesterol homeostasis"
Mouse model demonstrates cadmium promotes atherosclerosis through disruption of systemic and vascular cholesterol homeostasis, even at low doses.
PMID:41297938 SUPPORT Model Organism
"we identified miR-30d-5p and miR-504-3p as novel epigenetic regulators mediating Cd-induced foam cell formation. Specifically, Cd treatment upregulated miR-30d-5p and downregulated miR-504-3p, which directly targeted NCEH1 and CD36, respectively, thereby promoting intracellular lipid accumulation."
Identifies the molecular mechanism: cadmium modulates specific miRNAs that regulate cholesterol handling genes, driving foam cell formation and atherosclerotic plaque development.
PMID:41297938 SUPPORT Human Clinical
"plasma miR-30d-5p levels were positively associated with Cd exposure and partially mediated the Cd-stroke association, accounting for 16.4% of the total effect."
Human case-control study (494 ischemic stroke patients vs 494 controls) validates miR-30d-5p as a mediator of cadmium-induced stroke risk.
Acute Pulmonary Injury
Inhalation of cadmium fumes causes acute chemical pneumonitis with diffuse alveolar damage, pulmonary edema, and potentially fatal respiratory failure. Cadmium oxide fumes are particularly hazardous, causing delayed-onset (12-36 hours) acute lung injury that may progress to ARDS.
type II pneumocyte CL:0002063
inflammatory response GO:0006954 ↑ INCREASED
lung UBERON:0002048
Downstream
Acute Respiratory Distress Syndrome Diffuse alveolar damage and pulmonary edema from cadmium fume inhalation progress to acute respiratory distress syndrome.
Show evidence (2 references)
PMID:16933734 SUPPORT Human Clinical
"Heavy metal inhalation is a rare cause of acute lung injury. Among the various heavy metals, cadmium is more commonly known to cause acute lung injury."
Case report of acute lung injury from cadmium fume inhalation.
PMID:22349354 SUPPORT Human Clinical
"In both cases, multiple organ damage was observed, involving brain, lung, liver, kidney, red blood cells, and platelets"
Fatal cadmium poisoning cases with pulmonary involvement among multi-organ damage.
✶

Histopathology

5
Diffuse Alveolar Damage
In acute cadmium inhalation, the lungs show diffuse alveolar damage with hyaline membrane formation, alveolar edema, and type II pneumocyte hyperplasia. This is the histopathological correlate of the acute respiratory distress syndrome seen clinically.
Show evidence (2 references)
PMID:22349354 SUPPORT Human Clinical
"In both cases, multiple organ damage was observed, involving brain, lung, liver, kidney, red blood cells, and platelets"
Autopsy of two fatal cadmium poisoning cases confirmed lung involvement as part of multi-organ pathological damage.
PMID:16933734 SUPPORT Human Clinical
"Heavy metal inhalation is a rare cause of acute lung injury. Among the various heavy metals, cadmium is more commonly known to cause acute lung injury."
Case report of fatal cadmium inhalation with acute lung injury, the clinical manifestation of diffuse alveolar damage.
Renal Tubulointerstitial Disease and Fibrosis
The kidneys show proximal tubular cell necrosis with loss of brush border, tubulointerstitial inflammatory infiltrates, and progressive fibrosis. Cadmium accumulates in the renal cortex. Both cadmium and lead nephropathies are characterized by tubulointerstitial disease and fibrosis, though only early lead nephropathy shows nuclear inclusion bodies.
Show evidence (2 references)
PMID:22349354 SUPPORT Human Clinical
"In both cases, multiple organ damage was observed, involving brain, lung, liver, kidney, red blood cells, and platelets"
Autopsy findings confirm kidney as a major target organ in fatal cadmium poisoning.
PMID:19106433 SUPPORT Human Clinical
"both entities are characterized by tubulointerstitial disease and fibrosis, but only early lead nephropathy is characterized by the presence of proximal tubule nuclear inclusion bodies, due to the combination of lead with a lead binding-protein."
Review confirms tubulointerstitial disease and fibrosis as the characteristic renal histopathology of cadmium nephropathy, and distinguishes it from lead nephropathy by the absence of nuclear inclusion bodies.
Hepatocellular Degeneration
Liver pathology shows hepatocellular degeneration and necrosis with gross cadmium excess on tissue analysis. Cadmium accumulates in hepatocytes where it is initially bound to metallothionein; when this binding capacity is overwhelmed, free cadmium causes oxidative damage and cell death.
Show evidence (3 references)
PMID:22349354 SUPPORT Human Clinical
"In both cases, multiple organ damage was observed, involving brain, lung, liver, kidney, red blood cells, and platelets"
Autopsy confirmed liver involvement as part of multi-organ cadmium damage.
PMID:7426480 SUPPORT Human Clinical
"Examination of the liver both in life and after death showed a gross excess of cadmium. This was also found in the kidneys after death."
Liver biopsy and postmortem analysis confirmed gross cadmium accumulation in hepatic tissue.
PMID:41412331 SUPPORT Human Clinical
"Cadmium exposure affects liver health by inhibiting steatosis and promoting fibrosis, with renal and lipid metabolism factors acting as mediators, and diet influencing the outcomes."
NHANES cross-sectional study in adolescents demonstrates cadmium exposure promotes hepatic fibrosis, providing human epidemiological evidence for cadmium-induced hepatocellular damage.
Osteomalacic Bone Changes
Bone biopsy shows widened osteoid seams with defective mineralization, consistent with osteomalacia. In severe cases (itai-itai disease), vertebral bodies show structural changes from gross deformity. Bone biopsies are essential for confirming the diagnosis of osteomalacia in cadmium-exposed patients.
Show evidence (2 references)
PMID:7426480 SUPPORT Human Clinical
"Several bone biopsies and detailed metabolic studies showed typical severe osteomalacia"
Multiple bone biopsies in a cadmium-exposed worker confirmed typical severe osteomalacia on histological examination.
PMID:7426480 SUPPORT Human Clinical
"Previously unreported changes were present in the bones, especially the lumbar vertebrae which were probably more the result of gross bone deformity than cadmium deposition."
Histopathological examination revealed novel structural changes in vertebral bone, attributed to mechanical deformity from osteomalacia rather than direct cadmium deposition.
Intracellular Dense Lysosomal Particles
Transmission electron microscopy reveals a large number of dense lysosomal and phagocytic particles in the cytoplasm near the nucleus. This ultrastructural finding is observed across multiple organs and suggests intracellular cadmium sequestration in lysosomes, with potential genotoxic implications from proximity to the nucleus.
Show evidence (1 reference)
PMID:22349354 SUPPORT Human Clinical
"transmission electron microscopy revealed a large number of dense lysosomal and phagocytic particles in the cytoplasm near the nucleus, indicating the need for a genotoxic study of cadmium."
Ultrastructural finding on TEM showing characteristic perinuclear lysosomal cadmium accumulation, a distinctive histopathological marker of cadmium toxicity.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Cadmium Poisoning Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

9
Genitourinary 3
Renal Tubular Dysfunction VERY_FREQUENT Renal tubular dysfunction HP:0000124
Show evidence (2 references)
PMID:39111871 SUPPORT Human Clinical
"She had chronic renal failure with a high Cd exposure level and advanced renal tubular dysfunction."
Documents renal tubular dysfunction as a key manifestation of chronic cadmium exposure.
PMID:23800513 SUPPORT Human Clinical
"We report the case of a 48-year-old man who presented with severe osteoporosis, impaired renal function and acquired Fanconi syndrome."
Confirms acquired Fanconi syndrome from chronic cadmium toxicity.
Low-Molecular-Weight Proteinuria VERY_FREQUENT Proteinuria HP:0000093
Show evidence (2 references)
PMID:20354761 SUPPORT Human Clinical
"An early and sensitive manifestation of chronic Cd renal toxicity, which can be useful in individual and population screening, is impaired reabsorption of low molecular weight proteins (LMWP) (also a receptor-mediated process in the proximal tubule) such as retinol binding protein (RBP). This..."
Review identifies LMW proteinuria as the earliest and most sensitive marker of cadmium nephrotoxicity, suitable for population screening.
PMID:19106433 SUPPORT Human Clinical
"Cadmium nephrotoxicity is heralded by increased excretion of beta2-microglobulin, retinol binding protein and alpha1-microglobulin, indicative of decreased proximal tubule function."
Confirms the specific LMW proteins excreted in cadmium nephrotoxicity: beta-2-microglobulin, retinol binding protein, and alpha-1-microglobulin.
Chronic Kidney Disease FREQUENT Chronic kidney disease HP:0012622
Show evidence (1 reference)
PMID:39111871 SUPPORT Human Clinical
"She had chronic renal failure with a high Cd exposure level and advanced renal tubular dysfunction."
Documents chronic renal failure from cadmium exposure.
Metabolism 1
Hypophosphataemia FREQUENT Hypophosphatemia HP:0002148
Show evidence (1 reference)
PMID:31974582 SUPPORT Human Clinical
"Three silversmiths presented similarly with clinical, biochemical and radiological evidence of hypophosphataemic osteomalacia."
Confirms hypophosphataemia as the metabolic derangement underlying cadmium-induced osteomalacia.
Musculoskeletal 2
Osteomalacia FREQUENT Osteomalacia HP:0002749
Show evidence (2 references)
PMID:31974582 SUPPORT Human Clinical
"Three silversmiths presented similarly with clinical, biochemical and radiological evidence of hypophosphataemic osteomalacia."
Confirms hypophosphataemic osteomalacia from occupational cadmium exposure.
PMID:39111871 SUPPORT Human Clinical
"The shortening of height, bone deformities and fractures, abnormal bone metabolism suggesting osteomalacia, and renal anemia were also noted."
Documents osteomalacia with bone deformities and fractures in itai-itai disease.
Osteoporosis FREQUENT Osteoporosis HP:0000939
Show evidence (2 references)
PMID:23800513 SUPPORT Human Clinical
"We report the case of a 48-year-old man who presented with severe osteoporosis, impaired renal function and acquired Fanconi syndrome."
Case report of severe osteoporosis from chronic cadmium toxicity.
PMID:18072106 SUPPORT Human Clinical
"We will present a case of cadmium induced peripheral neuropathy, nephropathy, and decreased bone density."
Confirms decreased bone density (osteoporosis) from cadmium exposure.
Nervous System 1
Peripheral Neuropathy OCCASIONAL Peripheral neuropathy HP:0009830
Show evidence (2 references)
PMID:18072106 SUPPORT Human Clinical
"Cadmium is a neurotoxic and nephrotoxic heavy metal"
Identifies cadmium as a neurotoxic heavy metal causing peripheral neuropathy.
PMID:41453694 SUPPORT Human Clinical
"lead (Pb), cadmium (Cd), and arsenic (As) are pervasive environmental toxicants capable of entering the human body via multiple exposure routes, leading to profound neurotoxic effects."
Review of heavy metal neurotoxicity confirms cadmium produces profound neurotoxic effects through multiple exposure routes.
Respiratory 1
Acute Respiratory Distress Syndrome OCCASIONAL Acute respiratory distress syndrome HP:0033677
Primarily in acute inhalation exposure
Show evidence (2 references)
PMID:16933734 SUPPORT Human Clinical
"Heavy metal inhalation is a rare cause of acute lung injury. Among the various heavy metals, cadmium is more commonly known to cause acute lung injury."
Confirms cadmium as a cause of acute lung injury from inhalation.
PMID:41000307 SUPPORT Human Clinical
"For patients with concurrent lung and kidney involvement, mechanical ventilation and continuous renal replacement therapy (CRRT) may be required."
Systematic review confirms severe pulmonary involvement requiring mechanical ventilation.
Constitutional 1
Bone Pain FREQUENT Bone pain HP:0002653
Show evidence (2 references)
PMID:19341754 SUPPORT Human Clinical
"a bone disease with fractures and severe pain, the itai-itai disease, a form of Cd-induced renal osteomalacia, was identified in Japan."
Historical review identifies severe bone pain as the defining symptom of itai-itai disease, the archetypal chronic cadmium poisoning syndrome.
PMID:7426480 SUPPORT Human Clinical
"during the last 12 years of his life the patient had suffered increasing disability from gross bone disease. Several bone biopsies and detailed metabolic studies showed typical severe osteomalacia"
Case report documents 12 years of progressive bone pain and disability from cadmium-induced osteomalacia in an occupationally exposed worker.
💊

Medical Actions

5
Chelation Therapy
Action: chelation therapy Ontology label: chelator agent therapy MAXO:0001223
Agent: Edetic Acid NCIT:C61742 succimer CHEBI:63623 2,3-disulfanylpropane-1-sulfonic acid CHEBI:888
Chelating agents (CaNa2-EDTA, DMSA, DMPS) are used to bind and promote urinary excretion of cadmium. Effectiveness is limited due to cadmium's tight binding to metallothionein and intracellular sequestration. BAL (dimercaprol) is contraindicated as it may increase renal cadmium uptake.
Show evidence (2 references)
PMID:41000307 SUPPORT Human Clinical
"The treatment plan includes the use of chelating agents to reduce cadmium levels in the body and antibiotics to maintain the patient's condition."
Systematic review confirms chelating agents as part of standard cadmium poisoning treatment.
PMID:41453694 PARTIAL Human Clinical
"Conventional chelation therapy, when used long-term, can lead to renal and gastrointestinal diseases."
Review highlights significant limitations of conventional chelation therapy, noting long-term use can itself cause renal and gastrointestinal toxicity.
Phosphate Supplementation
Action: Pharmacotherapy NCIT:C15986
Agent: phosphate CHEBI:26020
Neutral phosphate supplements to correct hypophosphataemia from renal phosphate wasting. Phosphate replacement is essential for treating the underlying metabolic defect driving cadmium-induced osteomalacia and results in significant symptom improvement when combined with calcitriol.
Show evidence (1 reference)
PMID:31974582 SUPPORT Human Clinical
"They were initiated on neutral phosphate and calcitriol. On follow-up, they reported significant reduction in severity of symptoms."
Demonstrates effectiveness of phosphate supplementation (combined with calcitriol) for cadmium-induced osteomalacia.
Vitamin D and Calcium Supplementation
Action: vitamin D supplementation MAXO:0000110
Calcitriol (active vitamin D) supplementation to treat osteomalacia, bypassing the impaired renal 1-alpha-hydroxylation caused by cadmium nephrotoxicity. Calcium supplementation may also be required to address secondary hyperparathyroidism and calcium malabsorption.
Show evidence (3 references)
PMID:31974582 SUPPORT Human Clinical
"They were initiated on neutral phosphate and calcitriol. On follow-up, they reported significant reduction in severity of symptoms."
Demonstrates effectiveness of calcitriol for cadmium-induced osteomalacia.
PMID:41000307 SUPPORT Human Clinical
"for patients with osteochondropathy, supplementation with calcium and vitamin D is recommended."
Systematic review recommends calcium and vitamin D supplementation for skeletal complications.
PMID:7426480 SUPPORT Human Clinical
"typical severe osteomalacia, which responded well initially to calcium and vitamin D treatment."
Case report confirms initial good response to calcium and vitamin D in cadmium-induced osteomalacia.
Supportive ICU Care
Action: supportive care MAXO:0000950
For acute cadmium inhalation with pulmonary involvement, intensive care including mechanical ventilation for ARDS and continuous renal replacement therapy (CRRT) for concurrent renal failure may be required.
Show evidence (1 reference)
PMID:41000307 SUPPORT Human Clinical
"For patients with concurrent lung and kidney involvement, mechanical ventilation and continuous renal replacement therapy (CRRT) may be required."
Systematic review confirms need for ICU-level care in severe acute cadmium poisoning.
Exposure Cessation and Prevention
Removal from cadmium exposure source is essential. Occupational hygiene measures include adequate ventilation, personal protective equipment, and workplace monitoring. Public health interventions include environmental remediation of contaminated soil and water, and regulatory limits on cadmium in food and consumer products.
Show evidence (2 references)
PMID:23800513 SUPPORT Human Clinical
"Therefore, an early diagnosis and prevention of further exposure are important."
Emphasizes the importance of preventing further cadmium exposure given lack of effective treatment.
PMID:31974582 SUPPORT Human Clinical
"regulatory agencies and policy makers ought to survey the silver industry and ensure that the metals used are within permissible safe limits of exposure."
Calls for occupational regulation to prevent cadmium exposure in the silver industry.
🌍

Environmental Factors

4
Occupational Cadmium Exposure
exposure to cadmium ECTO:0001566 factory ENVO:01000536
Occupational exposure occurs in silver jewelry manufacturing, zinc smelting, battery production, cadmium plating, welding of cadmium-containing alloys, and pigment manufacturing. Workers inhale cadmium fumes and dust, with the silver cottage industry in developing countries being particularly hazardous due to lack of protective measures.
Show evidence (3 references)
PMID:18072106 SUPPORT Human Clinical
"Silver is mixed with cadmium and then used to make silver jewelry. During this process there is a formation of cadmium fumes, and the workers inhale the fumes."
Describes the mechanism of occupational cadmium exposure in the silver jewelry industry.
PMID:31974582 SUPPORT Human Clinical
"We highlight the occurrence of hypophosphataemic osteomalacia due to chronic cadmium exposure in the silver industry in India."
Confirms the silver industry as a source of chronic cadmium exposure.
PMID:41000307 SUPPORT Human Clinical
"cadmium poisoning primarily affects adult males and is often associated with occupational exposure."
Systematic review confirms occupational exposure as the primary route of cadmium poisoning.
Environmental Cadmium Contamination
exposure to cadmium ECTO:0001566
Environmental exposure through contaminated food (rice, vegetables grown in cadmium-polluted soil), drinking water, and ambient air near industrial sources. Mining and smelting operations contaminate local waterways and agricultural land, as in the Jinzu River basin in Japan.
Show evidence (1 reference)
PMID:39111871 SUPPORT Human Clinical
"An elderly female farmer with Cd nephropathy residing in a Cd-polluted area in the northern part of the Akita prefecture was identified through hospital-based screening"
Documents environmental cadmium exposure in an agricultural area with contaminated soil.
Tobacco Smoke Exposure
exposure to tobacco smoking ECTO:6000029
Tobacco smoke is a significant non-occupational source of cadmium. Tobacco plants accumulate cadmium from soil; a single cigarette may contain 1-2 mcg cadmium. Smokers typically have blood cadmium levels 4-5 times higher than non-smokers.
Show evidence (1 reference)
PMID:41000307 SUPPORT Human Clinical
"Common risk factors include smoking and alcohol consumption."
Systematic review identifies smoking as a common risk factor for cadmium poisoning.
Iron Deficiency as Risk Modifier
Low iron stores increase gastrointestinal cadmium absorption via shared divalent metal transporter 1 (DMT1). Iron-deficient individuals, often women and children, are at higher risk of cadmium accumulation from dietary sources.
Show evidence (1 reference)
PMID:41000307 SUPPORT Human Clinical
"The study also found that low iron stores exacerbate cadmium poisoning."
Systematic review confirms that iron deficiency exacerbates cadmium toxicity.
🔬

Biochemical Markers

5
Blood Cadmium Level (INCREASED)
Show evidence (1 reference)
PMID:41000307 SUPPORT Human Clinical
"Diagnosis relies on a combination of clinical diagnostic tests, blood and urine tests, chest X-rays, kidney ultrasounds, bone density measurements, and skeletal imaging."
Systematic review confirms blood cadmium testing as a key diagnostic tool.
Urinary Cadmium Level (INCREASED)
Show evidence (1 reference)
PMID:19364190 SUPPORT Human Clinical
"Conducting pre-flush testing is also currently the clinician's only means of identifying cadmium toxicity."
Identifies pre-challenge urine testing as the key diagnostic method for cadmium toxicity.
Urinary Beta-2-Microglobulin (INCREASED)
Show evidence (1 reference)
PMID:19106433 SUPPORT Human Clinical
"Cadmium nephrotoxicity is heralded by increased excretion of beta2-microglobulin, retinol binding protein and alpha1-microglobulin, indicative of decreased proximal tubule function."
Identifies beta-2-microglobulin excretion as a herald of cadmium nephrotoxicity.
Serum Phosphate (DECREASED)
Show evidence (1 reference)
PMID:31974582 SUPPORT Human Clinical
"Three silversmiths presented similarly with clinical, biochemical and radiological evidence of hypophosphataemic osteomalacia."
Confirms hypophosphataemia as a biochemical finding in cadmium-induced osteomalacia.
Hepatic Transaminases (ALT/AST) (INCREASED)
Show evidence (1 reference)
PMID:40164036 SUPPORT Model Organism
"exercise significantly decreased blood ALT and AST levels, alleviating oxidative stress in the liver by reducing MDA synthesis and enhancing SOD and GSH-PX activities."
Mouse model confirms cadmium-induced elevation of hepatic transaminases.
🔀

Differential Diagnoses

5

Conditions with similar clinical presentations that must be differentiated from Cadmium Poisoning:

Lead Poisoning MONDO:0018019
Overlapping Features Lead poisoning shares features with cadmium toxicity including renal tubular dysfunction, peripheral neuropathy, and occupational exposure in metalworking industries. However, lead poisoning characteristically produces basophilic stippling of erythrocytes, a lead line on gingiva, wrist/foot drop, and abdominal colic, which are not features of cadmium toxicity.
Distinguishing Features
  • Basophilic stippling of erythrocytes on blood smear
  • Lead line on gingiva (Burton line)
  • Wrist drop and foot drop from motor neuropathy (cadmium causes sensory neuropathy)
  • Abdominal colic (lead colic) is characteristic
  • Elevated blood lead levels rather than blood cadmium
  • Osteomalacia and severe phosphate wasting are not typical of lead poisoning
Show evidence (2 references)
PMID:19106433 SUPPORT Human Clinical
"Cadmium in sufficient cumulative dosage leads to the production of the Fanconi syndrome, a generalized proximal tubular reabsorptive defect thought to be related to inhibition of both ATP production and Na-K-ATPase activity. On the other hand, lead accumulation in the proximal tubule leads to..."
Directly contrasts cadmium vs lead nephrotoxicity, showing both settle in proximal tubule but produce different clinical manifestations.
PMID:19106433 SUPPORT Human Clinical
"Beta2-microglobulinuria is not found in lead nephropathy."
Key distinguishing feature: beta-2-microglobulinuria is a hallmark of cadmium nephrotoxicity but absent in lead nephropathy.
Other Causes of Acquired Fanconi Syndrome Not Yet Curated MONDO:0060779
Overlapping Features Acquired Fanconi syndrome can result from multiple causes beyond cadmium, including medications (tenofovir, ifosfamide, cisplatin, valproic acid), multiple myeloma with light chain deposition, and Wilson disease. The clinical presentation of proximal tubular dysfunction with LMW proteinuria, glucosuria, and aminoaciduria is identical regardless of cause.
Distinguishing Features
  • Medication history (tenofovir, cisplatin, ifosfamide) may explain tubular dysfunction
  • Multiple myeloma presents with monoclonal protein on serum/urine electrophoresis
  • Wilson disease shows low ceruloplasmin, elevated urine copper, and Kayser-Fleischer rings
  • Cadmium toxicity is distinguished by elevated blood/urine cadmium levels and occupational or environmental exposure history
Show evidence (1 reference)
PMID:23800513 SUPPORT Human Clinical
"He was finally diagnosed with chronic cadmium toxicity resulting from long-term occupational exposure."
Case illustrates how Fanconi syndrome presentation required occupational history and cadmium testing to distinguish from other causes.
Vitamin D Deficiency Osteomalacia Not Yet Curated MONDO:0100471
Overlapping Features Nutritional vitamin D deficiency causes osteomalacia with bone pain, proximal myopathy, and pathologic fractures that closely mimic cadmium- induced osteomalacia. Both conditions present with low serum phosphate and elevated alkaline phosphatase.
Distinguishing Features
  • Low serum 25-hydroxyvitamin D level (< 20 ng/mL)
  • No renal tubular dysfunction or LMW proteinuria
  • Normal urinary cadmium levels
  • Responds to vitamin D supplementation alone without phosphate replacement
  • No occupational heavy metal exposure history
Show evidence (2 references)
PMID:31974582 SUPPORT Human Clinical
"It is essential to maintain a high index of suspicion in diagnosing this condition. A thorough knowledge of the occupational background of patients, as well as ambient conditions at the workplace is of utmost importance in contemplating the possibility of such rare occurrences."
Emphasizes the need for occupational history to distinguish cadmium-induced osteomalacia from more common nutritional causes.
PMID:7426480 SUPPORT Human Clinical
"The mechanism of development of the severe acquired Fanconi syndrome was thought to be a combination of dietary calcium and vitamin D deficiency and impaired calcium absorption from abnormal vitamin D synthesis, related to the cadmium deposition in the renal tubules"
Demonstrates that cadmium-induced osteomalacia involves impaired renal vitamin D synthesis, making it difficult to distinguish from pure nutritional vitamin D deficiency without cadmium testing.
Metal Fume Fever
Overlapping Features Metal fume fever, typically caused by zinc oxide fume inhalation, presents with flu-like symptoms (fever, myalgias, metallic taste) hours after welding or metalworking. It mimics early acute cadmium inhalation but is self-limiting within 24-48 hours and does not progress to ARDS.
Distinguishing Features
  • Self-limiting course resolving within 24-48 hours
  • Does not progress to ARDS or respiratory failure
  • Typically caused by zinc rather than cadmium fumes
  • No renal or skeletal toxicity
  • Cadmium fume exposure causes delayed-onset (12-36 hours) progressive respiratory failure
Show evidence (1 reference)
PMID:16933734 SUPPORT Human Clinical
"Heavy metal inhalation is a rare cause of acute lung injury. Among the various heavy metals, cadmium is more commonly known to cause acute lung injury."
Cadmium fume inhalation causes true acute lung injury, unlike the benign self-limiting course of metal fume fever.
X-linked Hypophosphatemia MONDO:0020720
Overlapping Features X-linked hypophosphatemia (XLH) is an inherited disorder of renal phosphate wasting caused by PHEX gene mutations, leading to excess FGF23 and hypophosphataemic rickets/osteomalacia. It presents with similar phosphate wasting and skeletal findings but occurs from childhood without heavy metal exposure.
Distinguishing Features
  • Childhood onset with rickets, short stature, and bowing of lower limbs
  • Family history consistent with X-linked dominant inheritance
  • Elevated FGF23 levels
  • No LMW proteinuria or generalized Fanconi syndrome
  • Normal cadmium levels
  • No occupational or environmental exposure history
Show evidence (1 reference)
PMID:31974582 SUPPORT Human Clinical
"Three silversmiths presented similarly with clinical, biochemical and radiological evidence of hypophosphataemic osteomalacia."
Adult-onset hypophosphataemic osteomalacia from cadmium exposure contrasts with XLH, which presents in childhood; cadmium-induced phosphate wasting is acquired and accompanied by Fanconi syndrome.
📊

Related Datasets

1
The protease DDI2 regulates NRF1-metallothionein pathway in response to Cadmium toxicity in the liver geo:GSE198150
RNA-seq profiling of liver tissue from liver-specific Ddi2 knockout and wild-type mice, investigating how the protease DDI2 regulates the NRF1-metallothionein pathway in response to cadmium toxicity. Identifies DDI2-mediated metallothionein activation as a protective mechanism against cadmium-induced hepatotoxicity.
mouse BULK RNA SEQ n=4 Illumina HiSeq 2500
liver tissue
Conditions: Ddi2 liver-specific knockout wild-type control
PMID:36248746
2 replicates per condition (WT vs Ddi2-KO). Demonstrates that DDI2 cleaves and activates NRF1 to drive metallothionein expression in response to cadmium, linking proteasome homeostasis to heavy metal detoxification.
🔬

Clinical Trials

4
NCT05908383 PHASE_I COMPLETED
Phase I, randomized, double-blind, single-center, single-dose escalation trial evaluating the safety, tolerability, and pharmacokinetic characteristics of injectable GMDTC (a novel cadmium chelation agent) in healthy subjects. This is the foundational safety study for the GMDTC cadmium chelation program.
Show evidence (1 reference)
clinicaltrials:NCT05908383 SUPPORT Human Clinical
"This trial is a randomized, double-blind, single-center, single-dose escalating Phase I clinical trial designed to evaluate the safety, tolerability, and pharmacokinetic characteristics of injectable GMDTC in healthy subjects"
First-in-human safety trial for GMDTC, a novel chelation agent being developed specifically for cadmium poisoning.
NCT06199349 PHASE_I COMPLETED
Phase Ib trial evaluating the safety, tolerability, and pharmacokinetic characteristics of repeated-dose GMDTC injection in people with excessive cadmium levels. This trial extends the Phase I safety profile from healthy volunteers to the target population of cadmium-exposed individuals across three dose cohorts.
Target Phenotypes: Chronic kidney disease HP:0012622
Show evidence (1 reference)
clinicaltrials:NCT06199349 SUPPORT Human Clinical
"This trial is a randomized, double-blind, single-center, single-dose escalating Phase I clinical trial designed to evaluate the safety, tolerability, and pharmacokinetic characteristics of GMDTC for injection after repeated administration in people with excessive cadmium levels."
First trial of GMDTC chelation directly in cadmium-exposed individuals, establishing repeated-dose safety and pharmacokinetics in the target population.
NCT07057414 PHASE_II RECRUITING
Phase IIa, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of GMDTC injection in subjects with elevated cadmium levels. This is the first controlled efficacy trial of a chelation agent specifically developed for cadmium poisoning.
Target Phenotypes: Chronic kidney disease HP:0012622
Show evidence (1 reference)
clinicaltrials:NCT07057414 SUPPORT Human Clinical
"This is a randomized, double-blind, placebo-controlled, single-center Phase IIa clinical study."
First placebo-controlled efficacy trial for cadmium-specific chelation therapy, representing a significant advance given that no approved treatment exists for cadmium poisoning.
NCT00376987 PHASE_II COMPLETED
Clinical trial evaluating whether dietary zinc supplements can reduce serum cadmium levels in current cigarette smokers. Leverages the known competitive interaction between zinc and cadmium at shared divalent metal transporters (DMT1) to potentially reduce cadmium body burden through a simple dietary intervention.
Target Phenotypes: Proteinuria HP:0000093
Show evidence (1 reference)
clinicaltrials:NCT00376987 SUPPORT Human Clinical
"Zinc supplements may lower cadmium levels in smokers and may help prevent DNA damage."
Evaluates a non-chelation approach to reducing cadmium burden by exploiting zinc-cadmium competition at shared intestinal transporters.
{ }

Source YAML

click to show 
name: Cadmium Poisoning
creation_date: '2026-02-10T22:52:02Z'
updated_date: '2026-05-08T18:54:20Z'
description: >-
  Cadmium poisoning is a toxic condition resulting from acute or chronic exposure
  to cadmium, a heavy metal encountered primarily through occupational sources
  (silver jewelry industry, zinc smelting, battery manufacturing), contaminated
  food and water, and tobacco smoke. Acute inhalation of cadmium fumes causes
  severe pneumonitis and acute lung injury. Chronic exposure leads to progressive
  renal tubular dysfunction (Fanconi syndrome), hypophosphataemic osteomalacia,
  osteoporosis, and peripheral neuropathy. The most severe form of chronic cadmium
  toxicity is itai-itai disease, endemic in cadmium-polluted regions of Japan,
  characterized by severe bone pain, fractures, and renal failure. Cadmium has a
  long biological half-life (10-30 years) and there is no effective antidote;
  management centers on exposure cessation, chelation therapy, and supportive care.
category: Environmental
disease_term:
  preferred_term: cadmium poisoning
  term:
    id: MONDO:0043523
    label: cadmium poisoning
parents:
- heavy metal poisoning
has_subtypes:
- name: Acute
  display_name: Acute Cadmium Poisoning (Inhalation)
  description: >-
    Acute cadmium poisoning from inhalation of cadmium fumes or dust, typically
    occurring in occupational settings (welding, smelting, silver jewelry
    manufacturing). Presents with acute lung injury, chemical pneumonitis,
    pulmonary edema, and potentially fatal respiratory failure. Symptoms may be
    delayed 12-36 hours after exposure.
  evidence:
  - reference: PMID:16933734
    reference_title: "Acute lung injury due to cadmium inhalation--a case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Heavy metal inhalation is a rare cause of acute lung injury. Among the various heavy metals, cadmium is more commonly known to cause acute lung injury."
    explanation: "Confirms acute cadmium inhalation as a cause of acute lung injury."
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "For patients with concurrent lung and kidney involvement, mechanical ventilation and continuous renal replacement therapy (CRRT) may be required."
    explanation: "Systematic review confirms severe acute presentations requiring ventilatory support."
- name: Chronic
  display_name: Chronic Cadmium Poisoning (Itai-itai Disease)
  description: >-
    Chronic cadmium toxicity from prolonged low-level exposure via contaminated
    food, water, or occupational sources. Characterized by progressive renal
    tubular dysfunction, Fanconi syndrome, hypophosphataemic osteomalacia,
    osteoporosis, and pathologic fractures. Itai-itai disease represents the
    most severe form, endemic in cadmium-polluted areas of Japan.
  evidence:
  - reference: PMID:39111871
    reference_title: "A suspected case of \"itai-itai disease\" in a cadmium-polluted area in Akita prefecture, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Itai-itai disease is the most severe case of chronic cadmium (Cd) toxicity, which was endemic in Cd-polluted areas in the Jinzu River basin in Toyama prefecture, Japan."
    explanation: "Describes itai-itai disease as the most severe form of chronic cadmium toxicity."
  - reference: PMID:23800513
    reference_title: "Ailing bones and failing kidneys: a case of chronic cadmium toxicity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "He was finally diagnosed with chronic cadmium toxicity resulting from long-term occupational exposure."
    explanation: "Case report confirming chronic cadmium toxicity from occupational exposure with renal and skeletal manifestations."
pathophysiology:
- name: Cadmium Absorption and Systemic Distribution
  description: >-
    Cadmium enters the body via inhalation of fumes/dust or gastrointestinal
    absorption from contaminated food and water. Inhaled cadmium has 25-50%
    bioavailability; oral absorption is lower (3-8%) but enhanced by iron
    deficiency via shared divalent metal transporter 1 (DMT1). Once absorbed,
    cadmium distributes via the bloodstream bound to albumin and accumulates
    in liver, kidney, and bone with a biological half-life of 10-30 years.
  biological_processes:
  - preferred_term: cellular response to cadmium ion
    term:
      id: GO:0071276
      label: cellular response to cadmium ion
  evidence:
  - reference: PMID:23800513
    reference_title: "Ailing bones and failing kidneys: a case of chronic cadmium toxicity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cadmium has a long biological half-life and there is no effective treatment for people who are exposed to it."
    explanation: "Confirms cadmium's long biological half-life contributing to progressive systemic accumulation."
  - reference: PMID:22349354
    reference_title: "An investigation and pathological analysis of two fatal cases of cadmium poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In both cases, multiple organ damage was observed, involving brain, lung, liver, kidney, red blood cells, and platelets"
    explanation: "Autopsy findings confirm systemic cadmium distribution to multiple organs."
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The study also found that low iron stores exacerbate cadmium poisoning."
    explanation: "Confirms that iron deficiency enhances cadmium absorption via shared transport mechanisms."
  - reference: PMID:20204475
    reference_title: "Catch me if you can! Novel aspects of cadmium transport in mammalian cells."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "uptake of free Cd(2+) has been demonstrated for the Fe(2+)/H(+) cotransporter divalent metal transporter 1."
    explanation: "Demonstrates that cadmium enters cells via DMT1, the shared iron transporter explaining iron-deficiency enhanced absorption."
  - reference: PMID:31704329
    reference_title: "Cadmium-binding proteins in human blood plasma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "this is the first study to reveal cadmium-binding proteins in real human blood plasma, which is extremely critical to our understanding of cadmium transportation and accumulation in human blood."
    explanation: "First identification of cadmium-binding proteins (apolipoprotein A-I) in human plasma, elucidating blood transport mechanisms."
  downstream:
  - target: Hepatic Metallothionein Binding
    description: Absorbed cadmium is transported to the liver for initial processing
  - target: NF-kB/MAPK Inflammatory Signaling
    description: Cadmium ions directly activate inflammatory signaling cascades
  - target: Direct Osteoblast Toxicity
    description: Circulating cadmium has direct toxic effects on bone cells
  - target: Hepatic Glutathione Depletion
    description: Cadmium causes oxidative stress in hepatocytes
  - target: Cadmium-Induced Vascular Cholesterol Dysregulation
    description: Circulating cadmium disrupts vascular cholesterol homeostasis via miRNA modulation
- name: Hepatic Metallothionein Binding
  description: >-
    The liver is the primary site of initial cadmium detoxification.
    Hepatocytes synthesize metallothionein (MT), a cysteine-rich protein that
    binds cadmium with high affinity. The cadmium-metallothionein (Cd-MT)
    complex is slowly released into the bloodstream over time. While MT
    binding initially protects against free cadmium toxicity, the Cd-MT
    complex is filtered at the glomerulus and taken up by renal tubular cells,
    effectively transferring the cadmium burden to the kidney.
  cell_types:
  - preferred_term: hepatocyte
    term:
      id: CL:0000182
      label: hepatocyte
  locations:
  - preferred_term: liver
    term:
      id: UBERON:0002107
      label: liver
  biological_processes:
  - preferred_term: detoxification of inorganic compound
    term:
      id: GO:0061687
      label: detoxification of inorganic compound
  evidence:
  - reference: PMID:25042840
    reference_title: "Renal cells exposed to cadmium in vitro and in vivo: normalizing gene expression data."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "This half-life is partly as a result of metallothioneins (MTs), metal-binding proteins with a high affinity for Cd."
    explanation: "Confirms metallothionein as the primary cadmium-binding protein responsible for cadmium's long biological half-life."
  - reference: PMID:20354761
    reference_title: "Heavy metal poisoning: the effects of cadmium on the kidney."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The kidney is the main organ affected by chronic Cd exposure and toxicity. Cd accumulates in the kidney as a result of its preferential uptake by receptor-mediated endocytosis of freely filtered and metallothionein bound Cd (Cd-MT) in the renal proximal tubule."
    explanation: "Review confirms that hepatically-produced Cd-MT is filtered and taken up by the kidney, establishing the liver-to-kidney transfer pathway."
  downstream:
  - target: Renal Proximal Tubular Cadmium Uptake
    description: Cd-MT complex released from liver is filtered by glomerulus and reabsorbed by proximal tubule
- name: Renal Proximal Tubular Cadmium Uptake
  description: >-
    The cadmium-metallothionein (Cd-MT) complex is freely filtered at the
    glomerulus due to its small molecular weight (~7 kDa). Proximal tubular
    epithelial cells reabsorb Cd-MT via receptor-mediated endocytosis through
    the megalin/cubilin receptor complex. Once internalized, Cd-MT is degraded
    in lysosomes, releasing free cadmium ions intracellularly. This mechanism
    explains the kidney's particular vulnerability to cadmium accumulation.
  cell_types:
  - preferred_term: proximal tubule cell
    term:
      id: CL:0002306
      label: epithelial cell of proximal tubule
  locations:
  - preferred_term: proximal tubule
    term:
      id: UBERON:0004134
      label: proximal tubule
  biological_processes:
  - preferred_term: receptor-mediated endocytosis
    term:
      id: GO:0006898
      label: receptor-mediated endocytosis
  evidence:
  - reference: PMID:20204475
    reference_title: "Catch me if you can! Novel aspects of cadmium transport in mammalian cells."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the multiligand endocytic receptors megalin and cubilin take up cadmium-metallothionein complexes via receptor-mediated endocytosis."
    explanation: "Demonstrates that megalin and cubilin receptors mediate the endocytic uptake of Cd-MT complexes in proximal tubule."
  - reference: PMID:34298880
    reference_title: "Increased Endocytosis of Cadmium-Metallothionein through the 24p3 Receptor in an In Vivo Model with Reduced Proximal Tubular Activity."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Cd2+ complexed to metallothionein (MT) (CdMT) is taken up through receptor-mediated endocytosis (RME) via the PT receptor megalin:cubilin, which is the predominant pathway for reuptake of filtered proteins in the kidney."
    explanation: "Confirms megalin:cubilin as the predominant receptor for Cd-MT uptake in proximal tubule."
  - reference: PMID:20354761
    reference_title: "Heavy metal poisoning: the effects of cadmium on the kidney."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cd accumulates in the kidney as a result of its preferential uptake by receptor-mediated endocytosis of freely filtered and metallothionein bound Cd (Cd-MT) in the renal proximal tubule. Internalised Cd-MT is degraded in endosomes and lysosomes, releasing free Cd(2+) into the cytosol"
    explanation: "Review details the full Cd-MT uptake pathway: glomerular filtration, receptor-mediated endocytosis, lysosomal degradation, and free Cd2+ release."
  - reference: PMID:25042840
    reference_title: "Renal cells exposed to cadmium in vitro and in vivo: normalizing gene expression data."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "The high retention properties of the kidneys reside in proximal tubular cells that possess transport mechanisms for Cd-MT uptake, ultimately leading to more Cd accumulation."
    explanation: "Confirms proximal tubular cells possess specific transport mechanisms for Cd-MT uptake."
  downstream:
  - target: Proximal Tubular Cell Injury
    description: Accumulated free cadmium exceeds intracellular metallothionein binding capacity
- name: Proximal Tubular Cell Injury
  description: >-
    When intracellular cadmium exceeds the metallothionein binding capacity
    of proximal tubular cells (typically at renal cortex concentrations above
    200 mcg/g), free cadmium ions cause oxidative stress, mitochondrial
    dysfunction, and activation of apoptotic pathways. Cadmium displaces
    zinc from zinc-finger proteins and disrupts calcium signaling, leading
    to tubular cell death.
  cell_types:
  - preferred_term: proximal tubule cell
    term:
      id: CL:0002306
      label: epithelial cell of proximal tubule
  locations:
  - preferred_term: proximal tubule
    term:
      id: UBERON:0004134
      label: proximal tubule
  biological_processes:
  - preferred_term: apoptotic process
    modifier: INCREASED
    term:
      id: GO:0006915
      label: apoptotic process
  evidence:
  - reference: PMID:39111871
    reference_title: "A suspected case of \"itai-itai disease\" in a cadmium-polluted area in Akita prefecture, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "She had chronic renal failure with a high Cd exposure level and advanced renal tubular dysfunction."
    explanation: "Documents advanced renal tubular dysfunction resulting from proximal tubular cell injury in chronic cadmium exposure."
  - reference: PMID:20354761
    reference_title: "Heavy metal poisoning: the effects of cadmium on the kidney."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Internalised Cd-MT is degraded in endosomes and lysosomes, releasing free Cd(2+) into the cytosol, where it can generate reactive oxygen species (ROS) and activate cell death pathways."
    explanation: "Review details the mechanism of tubular cell injury: lysosomal release of free Cd2+ generates ROS and activates apoptosis."
  downstream:
  - target: Impaired Tubular Reabsorption
    description: Tubular cell injury and death cause loss of reabsorptive function
  - target: Chronic Kidney Disease Progression
    description: Sustained tubular injury leads to tubulointerstitial fibrosis
- name: Impaired Tubular Reabsorption
  description: >-
    Injury to proximal tubular cells causes Fanconi syndrome, characterized
    by impaired reabsorption of low-molecular-weight proteins (beta-2-
    microglobulin, retinol-binding protein), glucose, amino acids, uric acid,
    and phosphate. This is the earliest and most sensitive clinical indicator
    of chronic cadmium nephrotoxicity, detectable before decline in GFR.
  cell_types:
  - preferred_term: proximal tubule cell
    term:
      id: CL:0002306
      label: epithelial cell of proximal tubule
  locations:
  - preferred_term: kidney
    term:
      id: UBERON:0002113
      label: kidney
  biological_processes:
  - preferred_term: renal tubular reabsorption
    modifier: DECREASED
    term:
      id: GO:0070295
      label: renal water absorption
  evidence:
  - reference: PMID:23800513
    reference_title: "Ailing bones and failing kidneys: a case of chronic cadmium toxicity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We report the case of a 48-year-old man who presented with severe osteoporosis, impaired renal function and acquired Fanconi syndrome."
    explanation: "Case report confirming cadmium-induced acquired Fanconi syndrome with impaired tubular reabsorption."
  - reference: PMID:20576581
    reference_title: "Cadmium impairs albumin reabsorption by down-regulating megalin and ClC5 channels in renal proximal tubule cells."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Cd reduced the transcriptional expression of megalin and ClC5 and, at the same time, increased the degradation of megalin and ClC5 proteins via the lysosomal pathway in an in vitro model of renal proximal tubular cells."
    explanation: "Demonstrates the molecular mechanism: cadmium downregulates megalin and ClC5, the key receptors for protein reabsorption, explaining Fanconi syndrome."
  - reference: PMID:32244724
    reference_title: "In vitro Evaluation of The Effects of Cadmium on Endocytic Uptakes of Proteins into Cultured Proximal Tubule Epithelial Cells."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "The exposure of S1 and S2 cells to Cd at 1 and 3 µM for 3 days resulted in significant decreases in the uptakes of β2-MG and metallothionein but not in those of albumin or transferrin."
    explanation: "In vitro study directly demonstrates cadmium impairs endocytic uptake of low-molecular-weight proteins at nonlethal concentrations."
  - reference: PMID:20354761
    reference_title: "Heavy metal poisoning: the effects of cadmium on the kidney."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "An early and sensitive manifestation of chronic Cd renal toxicity, which can be useful in individual and population screening, is impaired reabsorption of low molecular weight proteins (LMWP)"
    explanation: "Review confirms impaired LMWP reabsorption as the earliest and most sensitive indicator of cadmium nephrotoxicity."
  downstream:
  - target: Renal Phosphate Wasting
    description: Impaired proximal tubular phosphate reabsorption causes phosphaturia
  - target: Renal Tubular Dysfunction
    description: Loss of proximal tubular reabsorptive function manifests as Fanconi syndrome (renal tubular dysfunction).
  - target: Low-Molecular-Weight Proteinuria
    description: Impaired receptor-mediated reabsorption of low-molecular-weight proteins (beta-2-microglobulin, retinol-binding protein) produces tubular proteinuria.
- name: Renal Phosphate Wasting
  description: >-
    Impaired proximal tubular phosphate reabsorption leads to chronic
    phosphaturia and hypophosphataemia. The sustained phosphate loss is the
    primary metabolic driver of cadmium-induced osteomalacia, as phosphate
    is essential for hydroxyapatite crystal formation in bone.
  locations:
  - preferred_term: proximal tubule
    term:
      id: UBERON:0004134
      label: proximal tubule
  biological_processes:
  - preferred_term: phosphate ion transport
    modifier: ABNORMAL
    term:
      id: GO:0006817
      label: phosphate ion transport
  evidence:
  - reference: PMID:31974582
    reference_title: "Hypophosphataemic osteomalacia due to cadmium exposure in the silver industry."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Three silversmiths presented similarly with clinical, biochemical and radiological evidence of hypophosphataemic osteomalacia."
    explanation: "Confirms hypophosphataemia from renal phosphate wasting as the driver of cadmium-induced osteomalacia."
  downstream:
  - target: Hypophosphataemia
    description: Sustained renal phosphate loss lowers serum phosphate, producing hypophosphataemia.
  - target: Defective Bone Mineralization
    description: Chronic hypophosphataemia impairs hydroxyapatite deposition in bone matrix
- name: Chronic Kidney Disease Progression
  description: >-
    Sustained proximal tubular injury from cadmium accumulation leads to
    tubulointerstitial inflammation, fibrosis, and progressive nephron loss.
    Glomerular filtration rate declines as tubulointerstitial nephritis
    advances, ultimately resulting in chronic kidney disease.
  locations:
  - preferred_term: kidney
    term:
      id: UBERON:0002113
      label: kidney
  evidence:
  - reference: PMID:39111871
    reference_title: "A suspected case of \"itai-itai disease\" in a cadmium-polluted area in Akita prefecture, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "She had chronic renal failure with a high Cd exposure level and advanced renal tubular dysfunction."
    explanation: "Documents progression to chronic renal failure from sustained cadmium-induced tubular damage."
  - reference: PMID:20354761
    reference_title: "Heavy metal poisoning: the effects of cadmium on the kidney."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Continued and heavy Cd exposure can progress to the clinical renal Fanconi syndrome, and ultimately to renal failure."
    explanation: "Review confirms the progressive nature of cadmium nephrotoxicity from tubular dysfunction to renal failure."
  downstream:
  - target: Chronic Kidney Disease
    description: Progressive tubulointerstitial nephritis and nephron loss reduce GFR, producing chronic kidney disease.
- name: Defective Bone Mineralization
  description: >-
    Chronic hypophosphataemia from renal phosphate wasting impairs
    hydroxyapatite crystal deposition in osteoid, causing osteomalacia.
    Bone becomes soft and prone to deformation and pathologic fractures.
    In itai-itai disease, severe demineralization causes fractures from
    minimal trauma, height loss, and skeletal deformities.
  locations:
  - preferred_term: bone
    term:
      id: UBERON:0002481
      label: bone tissue
  biological_processes:
  - preferred_term: bone mineralization
    modifier: DECREASED
    term:
      id: GO:0030282
      label: bone mineralization
  evidence:
  - reference: PMID:31974582
    reference_title: "Hypophosphataemic osteomalacia due to cadmium exposure in the silver industry."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Three silversmiths presented similarly with clinical, biochemical and radiological evidence of hypophosphataemic osteomalacia."
    explanation: "Confirms defective bone mineralization causing osteomalacia in cadmium-exposed workers."
  - reference: PMID:39111871
    reference_title: "A suspected case of \"itai-itai disease\" in a cadmium-polluted area in Akita prefecture, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The shortening of height, bone deformities and fractures, abnormal bone metabolism suggesting osteomalacia, and renal anemia were also noted."
    explanation: "Documents skeletal consequences of defective mineralization in itai-itai disease."
  downstream:
  - target: Osteomalacia
    description: Impaired hydroxyapatite deposition in osteoid produces osteomalacia (soft, undermineralized bone).
  - target: Bone Pain
    description: Osteomalacia and resulting pathologic fractures produce the severe bone pain characteristic of itai-itai disease.
- name: Direct Osteoblast Toxicity
  description: >-
    Cadmium directly inhibits osteoblast differentiation and function
    independently of the renal phosphate wasting pathway. Cadmium disrupts
    calcium signaling in osteoblasts, inhibits alkaline phosphatase activity,
    and promotes osteoclast-mediated resorption, contributing to osteoporosis
    even before significant renal damage develops.
  cell_types:
  - preferred_term: osteoblast
    term:
      id: CL:0000062
      label: osteoblast
  locations:
  - preferred_term: bone
    term:
      id: UBERON:0002481
      label: bone tissue
  biological_processes:
  - preferred_term: osteoblast differentiation
    modifier: DECREASED
    term:
      id: GO:0001649
      label: osteoblast differentiation
  evidence:
  - reference: PMID:18072106
    reference_title: "Cadmium exposure: health hazards of silver cottage industry in developing countries."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We will present a case of cadmium induced peripheral neuropathy, nephropathy, and decreased bone density."
    explanation: "Documents decreased bone density from cadmium exposure, consistent with direct bone cell toxicity."
  downstream:
  - target: Defective Bone Mineralization
    description: Impaired osteoblast function compounds the mineralization defect from phosphate wasting
  - target: Osteoporosis
    description: Direct osteoblast inhibition and enhanced osteoclastic resorption reduce bone mineral density, producing osteoporosis.
- name: Hepatic Glutathione Depletion
  description: >-
    Cadmium depletes hepatic glutathione stores and inhibits antioxidant
    enzymes (SOD, GSH-Px, CAT), disrupting the cellular redox balance.
    Lipid peroxidation increases (elevated MDA), and the glutathione
    metabolic pathway is overwhelmed. Cadmium also affects drug metabolism
    through altered cytochrome P450 activity.
  cell_types:
  - preferred_term: hepatocyte
    term:
      id: CL:0000182
      label: hepatocyte
  locations:
  - preferred_term: liver
    term:
      id: UBERON:0002107
      label: liver
  biological_processes:
  - preferred_term: glutathione metabolic process
    modifier: ABNORMAL
    term:
      id: GO:0006749
      label: glutathione metabolic process
  evidence:
  - reference: PMID:39381600
    reference_title: "Proteomic analysis of toxic effects of short-term cadmium exposure on goat livers."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "liver SOD, GSH-Px, T-AOC and CAT levels were decreased, and MDA level was increased in Cd-treated goats, and 630 DEPs (up 326, down 304) in the livers of Cd-treated goats."
    explanation: "Proteomic study in goats confirms cadmium-induced hepatic antioxidant depletion."
  - reference: PMID:40164036
    reference_title: "Exercise antagonizes cadmium-caused liver and intestinal injury in mice via Nrf2 and TLR2/NF-κB signalling pathway."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "exercise significantly decreased blood ALT and AST levels, alleviating oxidative stress in the liver by reducing MDA synthesis and enhancing SOD and GSH-PX activities."
    explanation: "Mouse model demonstrates cadmium-induced hepatic oxidative stress with depleted antioxidant enzymes."
  - reference: PMID:41188353
    reference_title: "Cadmium exposure during adolescence and young adulthood induces signatures of metabolic dysfunction-associated steatotic liver disease."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Cd exposure altered hepatic lipid homeostasis via the perturbation of steatosis gene expression and lipid species abundances. Additionally, Cd exposure triggered a hepatic antioxidant response"
    explanation: "Mouse model demonstrates cadmium triggers hepatic antioxidant response and disrupts lipid homeostasis, consistent with oxidative stress-driven liver injury."
  downstream:
  - target: Hepatocyte Apoptosis
    description: Oxidative stress from glutathione depletion triggers apoptotic cell death
- name: Hepatocyte Apoptosis
  description: >-
    Sustained oxidative stress from glutathione depletion triggers hepatocyte
    apoptosis via mitochondrial pathways. Cadmium causes release of pro-
    apoptotic proteins (cytochrome c, caspase-3, Bax) and nuclear damage,
    leading to progressive hepatocellular loss and liver injury.
  cell_types:
  - preferred_term: hepatocyte
    term:
      id: CL:0000182
      label: hepatocyte
  locations:
  - preferred_term: liver
    term:
      id: UBERON:0002107
      label: liver
  biological_processes:
  - preferred_term: apoptotic process
    modifier: INCREASED
    term:
      id: GO:0006915
      label: apoptotic process
  evidence:
  - reference: PMID:40164036
    reference_title: "Exercise antagonizes cadmium-caused liver and intestinal injury in mice via Nrf2 and TLR2/NF-κB signalling pathway."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Exercise inhibited nuclear damage and hepatocyte apoptosis caused by Cd by increasing Bcl-2 protein expression and preventing the release of pro-apoptotic proteins such as caspase-3, Cytc, Bax, caspase-8and cleaved-caspase-3."
    explanation: "Mouse model demonstrates cadmium-induced hepatocyte apoptosis via pro-apoptotic protein release."
- name: NF-kB/MAPK Inflammatory Signaling
  description: >-
    Cadmium activates pro-inflammatory signaling cascades including the NF-kB
    and MAPK/JNK pathways, leading to increased secretion of pro-inflammatory
    cytokines (IL-1beta, IL-6, TNF-alpha, IL-8, CCL2) and upregulation of
    COX-2. This chronic inflammatory state exacerbates organ-specific injury
    in kidney, liver, and intestine.
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:40191670
    reference_title: "Andrographolide Reduces Cytokine Release and Cyclooxygenase-2 Expression by Inhibiting the JNK and NF-κB Pathways in Glioblastoma Cells Exposed to Cadmium."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "the environmental pollutant cadmium is known to increase the secretion of pro-inflammatory cytokines, including interleukin (IL)-6, IL-8, and chemokine (C-C motif) ligand 2 (CCL2) by activating the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways."
    explanation: "In vitro study demonstrates cadmium activation of MAPK and NF-kB inflammatory pathways with cytokine secretion."
  - reference: PMID:40164036
    reference_title: "Exercise antagonizes cadmium-caused liver and intestinal injury in mice via Nrf2 and TLR2/NF-κB signalling pathway."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "exercise, both before and during Cd exposure, can reduce Cd caused pathological damages in the liver and duodenum of mice, suppressing the expression levels of the IL-1β, IL-6 and TNF-α genes."
    explanation: "Mouse model confirms cadmium-induced expression of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α."
  downstream:
  - target: Proximal Tubular Cell Injury
    description: Inflammatory cytokines exacerbate tubular cell damage
  - target: Hepatic Glutathione Depletion
    description: Inflammatory mediators compound hepatic oxidative stress
- name: Cadmium-Induced Vascular Cholesterol Dysregulation
  description: >-
    Cadmium disrupts cholesterol homeostasis in the vascular wall, promoting
    atherosclerosis through miRNA-mediated dysregulation of cholesterol uptake
    (CD36), efflux (ABCA1), and hydrolysis (NCEH1). Cadmium upregulates
    miR-30d-5p and downregulates miR-504-3p, promoting foam cell formation
    and intracellular lipid accumulation in macrophages. This pathway links
    cadmium exposure to increased cardiovascular risk, particularly ischemic
    stroke.
  biological_processes:
  - preferred_term: cholesterol homeostasis
    modifier: ABNORMAL
    term:
      id: GO:0042632
      label: cholesterol homeostasis
  evidence:
  - reference: PMID:41297938
    reference_title: "Cadmium Exposure Promotes Atherosclerosis by Disrupting Cholesterol Homeostasis via miR-30d-5p Regulation."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Cd exposure, even at a relatively low dosage (4 mg/L), significantly facilitates the progression of atherosclerosis in apolipoprotein E-deficient mice fed a high-fat diet. This pro-atherogenic effect was accompanied by comprehensive disturbances in systemic and vascular cholesterol homeostasis"
    explanation: "Mouse model demonstrates cadmium promotes atherosclerosis through disruption of systemic and vascular cholesterol homeostasis, even at low doses."
  - reference: PMID:41297938
    reference_title: "Cadmium Exposure Promotes Atherosclerosis by Disrupting Cholesterol Homeostasis via miR-30d-5p Regulation."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "we identified miR-30d-5p and miR-504-3p as novel epigenetic regulators mediating Cd-induced foam cell formation. Specifically, Cd treatment upregulated miR-30d-5p and downregulated miR-504-3p, which directly targeted NCEH1 and CD36, respectively, thereby promoting intracellular lipid accumulation."
    explanation: "Identifies the molecular mechanism: cadmium modulates specific miRNAs that regulate cholesterol handling genes, driving foam cell formation and atherosclerotic plaque development."
  - reference: PMID:41297938
    reference_title: "Cadmium Exposure Promotes Atherosclerosis by Disrupting Cholesterol Homeostasis via miR-30d-5p Regulation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "plasma miR-30d-5p levels were positively associated with Cd exposure and partially mediated the Cd-stroke association, accounting for 16.4% of the total effect."
    explanation: "Human case-control study (494 ischemic stroke patients vs 494 controls) validates miR-30d-5p as a mediator of cadmium-induced stroke risk."
- name: Acute Pulmonary Injury
  description: >-
    Inhalation of cadmium fumes causes acute chemical pneumonitis with diffuse
    alveolar damage, pulmonary edema, and potentially fatal respiratory failure.
    Cadmium oxide fumes are particularly hazardous, causing delayed-onset (12-36
    hours) acute lung injury that may progress to ARDS.
  cell_types:
  - preferred_term: type II pneumocyte
    term:
      id: CL:0002063
      label: pulmonary alveolar type 2 cell
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:16933734
    reference_title: "Acute lung injury due to cadmium inhalation--a case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Heavy metal inhalation is a rare cause of acute lung injury. Among the various heavy metals, cadmium is more commonly known to cause acute lung injury."
    explanation: "Case report of acute lung injury from cadmium fume inhalation."
  - reference: PMID:22349354
    reference_title: "An investigation and pathological analysis of two fatal cases of cadmium poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In both cases, multiple organ damage was observed, involving brain, lung, liver, kidney, red blood cells, and platelets"
    explanation: "Fatal cadmium poisoning cases with pulmonary involvement among multi-organ damage."
  downstream:
  - target: Acute Respiratory Distress Syndrome
    description: Diffuse alveolar damage and pulmonary edema from cadmium fume inhalation progress to acute respiratory distress syndrome.
phenotypes:
- category: Renal
  name: Renal Tubular Dysfunction
  frequency: VERY_FREQUENT
  diagnostic: true
  description: >-
    Proximal renal tubular dysfunction manifesting as Fanconi syndrome with
    low-molecular-weight proteinuria (beta-2-microglobulinuria), glucosuria,
    aminoaciduria, and phosphaturia. The earliest and most sensitive indicator
    of chronic cadmium nephrotoxicity.
  evidence:
  - reference: PMID:39111871
    reference_title: "A suspected case of \"itai-itai disease\" in a cadmium-polluted area in Akita prefecture, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "She had chronic renal failure with a high Cd exposure level and advanced renal tubular dysfunction."
    explanation: "Documents renal tubular dysfunction as a key manifestation of chronic cadmium exposure."
  - reference: PMID:23800513
    reference_title: "Ailing bones and failing kidneys: a case of chronic cadmium toxicity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We report the case of a 48-year-old man who presented with severe osteoporosis, impaired renal function and acquired Fanconi syndrome."
    explanation: "Confirms acquired Fanconi syndrome from chronic cadmium toxicity."
  phenotype_term:
    preferred_term: Renal tubular dysfunction
    term:
      id: HP:0000124
      label: Renal tubular dysfunction
- category: Renal
  name: Low-Molecular-Weight Proteinuria
  frequency: VERY_FREQUENT
  diagnostic: true
  description: >-
    Increased urinary excretion of low-molecular-weight proteins (beta-2-
    microglobulin, retinol-binding protein, alpha-1-microglobulin) reflecting
    impaired proximal tubular reabsorption. A hallmark biomarker of cadmium
    nephrotoxicity used for screening in exposed populations.
  evidence:
  - reference: PMID:20354761
    reference_title: "Heavy metal poisoning: the effects of cadmium on the kidney."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "An early and sensitive manifestation of chronic Cd renal toxicity, which can be useful in individual and population screening, is impaired reabsorption of low molecular weight proteins (LMWP) (also a receptor-mediated process in the proximal tubule) such as retinol binding protein (RBP). This so-called 'tubular proteinuria' is a good index of proximal tubular damage"
    explanation: "Review identifies LMW proteinuria as the earliest and most sensitive marker of cadmium nephrotoxicity, suitable for population screening."
  - reference: PMID:19106433
    reference_title: "Nephrotoxicity of cadmium & lead."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cadmium nephrotoxicity is heralded by increased excretion of beta2-microglobulin, retinol binding protein and alpha1-microglobulin, indicative of decreased proximal tubule function."
    explanation: "Confirms the specific LMW proteins excreted in cadmium nephrotoxicity: beta-2-microglobulin, retinol binding protein, and alpha-1-microglobulin."
  phenotype_term:
    preferred_term: Proteinuria
    term:
      id: HP:0000093
      label: Proteinuria
- category: Musculoskeletal
  name: Osteomalacia
  frequency: FREQUENT
  description: >-
    Defective bone mineralization caused by cadmium-induced renal phosphate
    wasting, leading to hypophosphataemia. Presents with bone pain, proximal
    muscle weakness, waddling gait, and pathologic fractures.
  evidence:
  - reference: PMID:31974582
    reference_title: "Hypophosphataemic osteomalacia due to cadmium exposure in the silver industry."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Three silversmiths presented similarly with clinical, biochemical and radiological evidence of hypophosphataemic osteomalacia."
    explanation: "Confirms hypophosphataemic osteomalacia from occupational cadmium exposure."
  - reference: PMID:39111871
    reference_title: "A suspected case of \"itai-itai disease\" in a cadmium-polluted area in Akita prefecture, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The shortening of height, bone deformities and fractures, abnormal bone metabolism suggesting osteomalacia, and renal anemia were also noted."
    explanation: "Documents osteomalacia with bone deformities and fractures in itai-itai disease."
  phenotype_term:
    preferred_term: Osteomalacia
    term:
      id: HP:0002749
      label: Osteomalacia
- category: Musculoskeletal
  name: Osteoporosis
  frequency: FREQUENT
  description: >-
    Decreased bone mineral density from combined effects of renal phosphate and
    calcium wasting, direct cadmium toxicity to osteoblasts, and secondary
    hyperparathyroidism. Contributes to pathologic fractures, particularly in
    chronic exposure.
  evidence:
  - reference: PMID:23800513
    reference_title: "Ailing bones and failing kidneys: a case of chronic cadmium toxicity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We report the case of a 48-year-old man who presented with severe osteoporosis, impaired renal function and acquired Fanconi syndrome."
    explanation: "Case report of severe osteoporosis from chronic cadmium toxicity."
  - reference: PMID:18072106
    reference_title: "Cadmium exposure: health hazards of silver cottage industry in developing countries."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We will present a case of cadmium induced peripheral neuropathy, nephropathy, and decreased bone density."
    explanation: "Confirms decreased bone density (osteoporosis) from cadmium exposure."
  phenotype_term:
    preferred_term: Osteoporosis
    term:
      id: HP:0000939
      label: Osteoporosis
- category: Musculoskeletal
  name: Bone Pain
  frequency: FREQUENT
  description: >-
    Severe bone pain, particularly in the legs, pelvis, and spine. The hallmark
    symptom of itai-itai disease (literally "it hurts, it hurts" disease).
    Results from osteomalacia and pathologic fractures.
  evidence:
  - reference: PMID:19341754
    reference_title: "Historical perspectives on cadmium toxicology."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "a bone disease with fractures and severe pain, the itai-itai disease, a form of Cd-induced renal osteomalacia, was identified in Japan."
    explanation: "Historical review identifies severe bone pain as the defining symptom of itai-itai disease, the archetypal chronic cadmium poisoning syndrome."
  - reference: PMID:7426480
    reference_title: "Cadmium-induced osteomalacia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "during the last 12 years of his life the patient had suffered increasing disability from gross bone disease. Several bone biopsies and detailed metabolic studies showed typical severe osteomalacia"
    explanation: "Case report documents 12 years of progressive bone pain and disability from cadmium-induced osteomalacia in an occupationally exposed worker."
  phenotype_term:
    preferred_term: Bone pain
    term:
      id: HP:0002653
      label: Bone pain
- category: Metabolic
  name: Hypophosphataemia
  frequency: FREQUENT
  description: >-
    Low serum phosphate levels resulting from impaired proximal tubular phosphate
    reabsorption. A key driver of cadmium-induced osteomalacia and a diagnostic
    clue when found with renal tubular dysfunction.
  evidence:
  - reference: PMID:31974582
    reference_title: "Hypophosphataemic osteomalacia due to cadmium exposure in the silver industry."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Three silversmiths presented similarly with clinical, biochemical and radiological evidence of hypophosphataemic osteomalacia."
    explanation: "Confirms hypophosphataemia as the metabolic derangement underlying cadmium-induced osteomalacia."
  phenotype_term:
    preferred_term: Hypophosphatemia
    term:
      id: HP:0002148
      label: Hypophosphatemia
- category: Renal
  name: Chronic Kidney Disease
  frequency: FREQUENT
  description: >-
    Progressive decline in renal function from chronic cadmium accumulation.
    Glomerular filtration rate declines as tubular damage progresses to
    tubulointerstitial nephritis.
  evidence:
  - reference: PMID:39111871
    reference_title: "A suspected case of \"itai-itai disease\" in a cadmium-polluted area in Akita prefecture, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "She had chronic renal failure with a high Cd exposure level and advanced renal tubular dysfunction."
    explanation: "Documents chronic renal failure from cadmium exposure."
  phenotype_term:
    preferred_term: Chronic kidney disease
    term:
      id: HP:0012622
      label: Chronic kidney disease
- category: Neurological
  name: Peripheral Neuropathy
  frequency: OCCASIONAL
  description: >-
    Cadmium-induced peripheral neuropathy, reflecting cadmium's neurotoxic
    properties. Reported in occupationally exposed workers in the silver
    jewelry industry.
  evidence:
  - reference: PMID:18072106
    reference_title: "Cadmium exposure: health hazards of silver cottage industry in developing countries."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cadmium is a neurotoxic and nephrotoxic heavy metal"
    explanation: "Identifies cadmium as a neurotoxic heavy metal causing peripheral neuropathy."
  - reference: PMID:41453694
    reference_title: "Advances in understanding the neurotoxicity of lead, cadmium, arsenic, and therapeutic strategies."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "lead (Pb), cadmium (Cd), and arsenic (As) are pervasive environmental toxicants capable of entering the human body via multiple exposure routes, leading to profound neurotoxic effects."
    explanation: "Review of heavy metal neurotoxicity confirms cadmium produces profound neurotoxic effects through multiple exposure routes."
  phenotype_term:
    preferred_term: Peripheral neuropathy
    term:
      id: HP:0009830
      label: Peripheral neuropathy
- category: Pulmonary
  name: Acute Respiratory Distress Syndrome
  frequency: OCCASIONAL
  notes: Primarily in acute inhalation exposure
  description: >-
    Acute respiratory distress syndrome from cadmium fume inhalation. May be
    fatal and often presents with delayed onset after initial asymptomatic period.
    Requires mechanical ventilation and intensive care support.
  evidence:
  - reference: PMID:16933734
    reference_title: "Acute lung injury due to cadmium inhalation--a case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Heavy metal inhalation is a rare cause of acute lung injury. Among the various heavy metals, cadmium is more commonly known to cause acute lung injury."
    explanation: "Confirms cadmium as a cause of acute lung injury from inhalation."
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "For patients with concurrent lung and kidney involvement, mechanical ventilation and continuous renal replacement therapy (CRRT) may be required."
    explanation: "Systematic review confirms severe pulmonary involvement requiring mechanical ventilation."
  phenotype_term:
    preferred_term: Acute respiratory distress syndrome
    term:
      id: HP:0033677
      label: Acute respiratory distress syndrome
biochemical:
- name: Blood Cadmium Level
  presence: INCREASED
  biomarker_term:
    preferred_term: cadmium(2+)
    term:
      id: CHEBI:48775
      label: cadmium(2+)
  notes: >-
    Blood cadmium levels reflect recent exposure. Normal levels are typically
    below 5 mcg/L. Levels above 50 mcg/L indicate significant toxicity. Blood
    cadmium testing is essential for confirming diagnosis.
  evidence:
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Diagnosis relies on a combination of clinical diagnostic tests, blood and urine tests, chest X-rays, kidney ultrasounds, bone density measurements, and skeletal imaging."
    explanation: "Systematic review confirms blood cadmium testing as a key diagnostic tool."
- name: Urinary Cadmium Level
  presence: INCREASED
  biomarker_term:
    preferred_term: cadmium(2+)
    term:
      id: CHEBI:48775
      label: cadmium(2+)
  notes: >-
    Urinary cadmium reflects total body burden and chronic exposure. Pre-
    challenge (unstimulated) urine testing is the primary method for identifying
    cadmium toxicity. Post-chelation challenge testing reflects total body
    stores and helps guide treatment.
  evidence:
  - reference: PMID:19364190
    reference_title: "The benefits of pre- and post-challenge urine heavy metal testing: Part 1."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Conducting pre-flush testing is also currently the clinician's only means of identifying cadmium toxicity."
    explanation: "Identifies pre-challenge urine testing as the key diagnostic method for cadmium toxicity."
- name: Urinary Beta-2-Microglobulin
  presence: INCREASED
  biomarker_term:
    preferred_term: Beta-2-Microglobulin
    term:
      id: NCIT:C62657
      label: Beta-2-Microglobulin
  notes: >-
    Elevated urinary beta-2-microglobulin is the most sensitive biomarker of
    cadmium-induced proximal tubular damage, reflecting impaired tubular protein
    reabsorption.
  evidence:
  - reference: PMID:19106433
    reference_title: "Nephrotoxicity of cadmium & lead."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cadmium nephrotoxicity is heralded by increased excretion of beta2-microglobulin, retinol binding protein and alpha1-microglobulin, indicative of decreased proximal tubule function."
    explanation: "Identifies beta-2-microglobulin excretion as a herald of cadmium nephrotoxicity."
- name: Serum Phosphate
  presence: DECREASED
  biomarker_term:
    preferred_term: phosphate ion
    term:
      id: CHEBI:35780
      label: phosphate ion
  notes: >-
    Low serum phosphate from renal phosphate wasting, driving osteomalacia.
  evidence:
  - reference: PMID:31974582
    reference_title: "Hypophosphataemic osteomalacia due to cadmium exposure in the silver industry."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Three silversmiths presented similarly with clinical, biochemical and radiological evidence of hypophosphataemic osteomalacia."
    explanation: "Confirms hypophosphataemia as a biochemical finding in cadmium-induced osteomalacia."
- name: Hepatic Transaminases (ALT/AST)
  presence: INCREASED
  biomarker_term:
    preferred_term: Alanine Aminotransferase
    term:
      id: NCIT:C25293
      label: Alanine Aminotransferase
  notes: >-
    Elevated ALT and AST levels reflecting hepatocellular injury from cadmium
    hepatotoxicity.
  evidence:
  - reference: PMID:40164036
    reference_title: "Exercise antagonizes cadmium-caused liver and intestinal injury in mice via Nrf2 and TLR2/NF-κB signalling pathway."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "exercise significantly decreased blood ALT and AST levels, alleviating oxidative stress in the liver by reducing MDA synthesis and enhancing SOD and GSH-PX activities."
    explanation: "Mouse model confirms cadmium-induced elevation of hepatic transaminases."
diagnosis:
- name: Blood Cadmium Level
  description: >-
    Blood cadmium reflects recent exposure. Normal levels are typically below
    5 mcg/L; levels above 50 mcg/L indicate significant toxicity. Blood
    cadmium is the initial screening test in suspected acute or occupational
    exposure.
  diagnosis_term:
    preferred_term: blood chemistry measurement
    term:
      id: MAXO:0000787
      label: blood chemistry measurement
  evidence:
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Diagnosis relies on a combination of clinical diagnostic tests, blood and urine tests, chest X-rays, kidney ultrasounds, bone density measurements, and skeletal imaging."
    explanation: "Systematic review confirms blood testing as part of the diagnostic workup."
- name: Urine Cadmium Level
  description: >-
    Urinary cadmium reflects total body burden and chronic exposure. Pre-
    challenge (unstimulated) urine cadmium is the primary method for
    identifying chronic cadmium toxicity. Post-chelation challenge testing
    reflects total body stores and helps guide treatment decisions.
  diagnosis_term:
    preferred_term: urine chemistry measurement
    term:
      id: MAXO:0000789
      label: urine chemistry measurement
  evidence:
  - reference: PMID:19364190
    reference_title: "The benefits of pre- and post-challenge urine heavy metal testing: Part 1."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Conducting pre-flush testing is also currently the clinician's only means of identifying cadmium toxicity."
    explanation: "Identifies pre-challenge urine testing as the key diagnostic method for cadmium toxicity."
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Diagnosis relies on a combination of clinical diagnostic tests, blood and urine tests, chest X-rays, kidney ultrasounds, bone density measurements, and skeletal imaging."
    explanation: "Systematic review confirms urine testing as part of the diagnostic workup."
- name: Urinary Beta-2-Microglobulin
  description: >-
    Urinary beta-2-microglobulin is used to detect cadmium-related proximal
    tubular dysfunction, complementing blood and urine cadmium measurements.
  diagnosis_term:
    preferred_term: urine chemistry measurement
    term:
      id: MAXO:0000789
      label: urine chemistry measurement
  markers: beta-2-microglobulin
  results: Increased urinary beta-2-microglobulin indicates proximal tubular injury.
  evidence:
  - reference: PMID:19106433
    reference_title: "Nephrotoxicity of cadmium & lead."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cadmium nephrotoxicity is heralded by increased excretion of beta2-microglobulin, retinol binding protein and alpha1-microglobulin, indicative of decreased proximal tubule function."
    explanation: This supports urinary beta-2-microglobulin as a renal tubular injury marker in cadmium toxicity.
- name: Skeletal Imaging
  description: >-
    Bone density measurements (DEXA scan) reveal osteoporosis and osteomalacia.
    Skeletal radiographs may show pseudofractures (Looser zones) characteristic
    of osteomalacia. Essential for evaluating the skeletal complications of
    chronic cadmium exposure.
  diagnosis_term:
    preferred_term: radiograph imaging procedure
    term:
      id: MAXO:0000595
      label: radiograph imaging procedure
  evidence:
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Diagnosis relies on a combination of clinical diagnostic tests, blood and urine tests, chest X-rays, kidney ultrasounds, bone density measurements, and skeletal imaging."
    explanation: "Systematic review confirms bone density measurements and skeletal imaging as part of diagnostic evaluation."
- name: Renal Imaging
  description: >-
    Kidney ultrasound assesses renal parenchymal damage, cortical thinning,
    and structural changes from chronic cadmium nephrotoxicity. Useful for
    monitoring disease progression in chronically exposed individuals.
  diagnosis_term:
    preferred_term: renal ultrasonography
    term:
      id: MAXO:0010217
      label: renal ultrasonography
  evidence:
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Diagnosis relies on a combination of clinical diagnostic tests, blood and urine tests, chest X-rays, kidney ultrasounds, bone density measurements, and skeletal imaging."
    explanation: "Systematic review confirms kidney ultrasound as part of the diagnostic workup."
- name: Chest Imaging
  description: >-
    Chest X-ray is important for evaluating acute pulmonary injury from
    cadmium fume inhalation, showing diffuse bilateral infiltrates consistent
    with chemical pneumonitis or ARDS.
  diagnosis_term:
    preferred_term: chest radiograph procedure
    term:
      id: MAXO:0010356
      label: chest radiograph procedure
  evidence:
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Diagnosis relies on a combination of clinical diagnostic tests, blood and urine tests, chest X-rays, kidney ultrasounds, bone density measurements, and skeletal imaging."
    explanation: "Systematic review confirms chest X-ray as part of the diagnostic evaluation."
treatments:
- name: Chelation Therapy
  description: >-
    Chelating agents (CaNa2-EDTA, DMSA, DMPS) are used to bind and promote
    urinary excretion of cadmium. Effectiveness is limited due to cadmium's
    tight binding to metallothionein and intracellular sequestration. BAL
    (dimercaprol) is contraindicated as it may increase renal cadmium uptake.
  treatment_term:
    preferred_term: chelation therapy
    term:
      id: MAXO:0001223
      label: chelator agent therapy
    therapeutic_agent:
    - preferred_term: Edetic Acid
      term:
        id: NCIT:C61742
        label: Edetic Acid
    - preferred_term: succimer
      term:
        id: CHEBI:63623
        label: succimer
    - preferred_term: 2,3-disulfanylpropane-1-sulfonic acid
      term:
        id: CHEBI:888
        label: 2,3-disulfanylpropane-1-sulfonic acid
  evidence:
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The treatment plan includes the use of chelating agents to reduce cadmium levels in the body and antibiotics to maintain the patient's condition."
    explanation: "Systematic review confirms chelating agents as part of standard cadmium poisoning treatment."
  - reference: PMID:41453694
    reference_title: "Advances in understanding the neurotoxicity of lead, cadmium, arsenic, and therapeutic strategies."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Conventional chelation therapy, when used long-term, can lead to renal and gastrointestinal diseases."
    explanation: "Review highlights significant limitations of conventional chelation therapy, noting long-term use can itself cause renal and gastrointestinal toxicity."
- name: Phosphate Supplementation
  description: >-
    Neutral phosphate supplements to correct hypophosphataemia from renal
    phosphate wasting. Phosphate replacement is essential for treating the
    underlying metabolic defect driving cadmium-induced osteomalacia and
    results in significant symptom improvement when combined with calcitriol.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: phosphate
      term:
        id: CHEBI:26020
        label: phosphate
  evidence:
  - reference: PMID:31974582
    reference_title: "Hypophosphataemic osteomalacia due to cadmium exposure in the silver industry."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "They were initiated on neutral phosphate and calcitriol. On follow-up, they reported significant reduction in severity of symptoms."
    explanation: "Demonstrates effectiveness of phosphate supplementation (combined with calcitriol) for cadmium-induced osteomalacia."
- name: Vitamin D and Calcium Supplementation
  description: >-
    Calcitriol (active vitamin D) supplementation to treat osteomalacia,
    bypassing the impaired renal 1-alpha-hydroxylation caused by cadmium
    nephrotoxicity. Calcium supplementation may also be required to address
    secondary hyperparathyroidism and calcium malabsorption.
  treatment_term:
    preferred_term: vitamin D supplementation
    term:
      id: MAXO:0000110
      label: vitamin D supplementation
  evidence:
  - reference: PMID:31974582
    reference_title: "Hypophosphataemic osteomalacia due to cadmium exposure in the silver industry."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "They were initiated on neutral phosphate and calcitriol. On follow-up, they reported significant reduction in severity of symptoms."
    explanation: "Demonstrates effectiveness of calcitriol for cadmium-induced osteomalacia."
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "for patients with osteochondropathy, supplementation with calcium and vitamin D is recommended."
    explanation: "Systematic review recommends calcium and vitamin D supplementation for skeletal complications."
  - reference: PMID:7426480
    reference_title: "Cadmium-induced osteomalacia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "typical severe osteomalacia, which responded well initially to calcium and vitamin D treatment."
    explanation: "Case report confirms initial good response to calcium and vitamin D in cadmium-induced osteomalacia."
- name: Supportive ICU Care
  description: >-
    For acute cadmium inhalation with pulmonary involvement, intensive care
    including mechanical ventilation for ARDS and continuous renal replacement
    therapy (CRRT) for concurrent renal failure may be required.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  evidence:
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "For patients with concurrent lung and kidney involvement, mechanical ventilation and continuous renal replacement therapy (CRRT) may be required."
    explanation: "Systematic review confirms need for ICU-level care in severe acute cadmium poisoning."
- name: Exposure Cessation and Prevention
  description: >-
    Removal from cadmium exposure source is essential. Occupational hygiene
    measures include adequate ventilation, personal protective equipment, and
    workplace monitoring. Public health interventions include environmental
    remediation of contaminated soil and water, and regulatory limits on
    cadmium in food and consumer products.
  evidence:
  - reference: PMID:23800513
    reference_title: "Ailing bones and failing kidneys: a case of chronic cadmium toxicity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Therefore, an early diagnosis and prevention of further exposure are important."
    explanation: "Emphasizes the importance of preventing further cadmium exposure given lack of effective treatment."
  - reference: PMID:31974582
    reference_title: "Hypophosphataemic osteomalacia due to cadmium exposure in the silver industry."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "regulatory agencies and policy makers ought to survey the silver industry and ensure that the metals used are within permissible safe limits of exposure."
    explanation: "Calls for occupational regulation to prevent cadmium exposure in the silver industry."
environmental:
- name: Occupational Cadmium Exposure
  exposure_term:
    preferred_term: exposure to cadmium
    term:
      id: ECTO:0001566
      label: exposure to cadmium
  environment_context:
    preferred_term: factory
    term:
      id: ENVO:01000536
      label: factory
  description: >-
    Occupational exposure occurs in silver jewelry manufacturing, zinc smelting,
    battery production, cadmium plating, welding of cadmium-containing alloys,
    and pigment manufacturing. Workers inhale cadmium fumes and dust, with the
    silver cottage industry in developing countries being particularly hazardous
    due to lack of protective measures.
  evidence:
  - reference: PMID:18072106
    reference_title: "Cadmium exposure: health hazards of silver cottage industry in developing countries."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Silver is mixed with cadmium and then used to make silver jewelry. During this process there is a formation of cadmium fumes, and the workers inhale the fumes."
    explanation: "Describes the mechanism of occupational cadmium exposure in the silver jewelry industry."
  - reference: PMID:31974582
    reference_title: "Hypophosphataemic osteomalacia due to cadmium exposure in the silver industry."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We highlight the occurrence of hypophosphataemic osteomalacia due to chronic cadmium exposure in the silver industry in India."
    explanation: "Confirms the silver industry as a source of chronic cadmium exposure."
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "cadmium poisoning primarily affects adult males and is often associated with occupational exposure."
    explanation: "Systematic review confirms occupational exposure as the primary route of cadmium poisoning."
- name: Environmental Cadmium Contamination
  exposure_term:
    preferred_term: exposure to cadmium
    term:
      id: ECTO:0001566
      label: exposure to cadmium
  description: >-
    Environmental exposure through contaminated food (rice, vegetables grown in
    cadmium-polluted soil), drinking water, and ambient air near industrial
    sources. Mining and smelting operations contaminate local waterways and
    agricultural land, as in the Jinzu River basin in Japan.
  evidence:
  - reference: PMID:39111871
    reference_title: "A suspected case of \"itai-itai disease\" in a cadmium-polluted area in Akita prefecture, Japan."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "An elderly female farmer with Cd nephropathy residing in a Cd-polluted area in the northern part of the Akita prefecture was identified through hospital-based screening"
    explanation: "Documents environmental cadmium exposure in an agricultural area with contaminated soil."
- name: Tobacco Smoke Exposure
  exposure_term:
    preferred_term: exposure to tobacco smoking
    term:
      id: ECTO:6000029
      label: exposure to tobacco smoking
  description: >-
    Tobacco smoke is a significant non-occupational source of cadmium. Tobacco
    plants accumulate cadmium from soil; a single cigarette may contain 1-2 mcg
    cadmium. Smokers typically have blood cadmium levels 4-5 times higher than
    non-smokers.
  evidence:
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Common risk factors include smoking and alcohol consumption."
    explanation: "Systematic review identifies smoking as a common risk factor for cadmium poisoning."
- name: Iron Deficiency as Risk Modifier
  description: >-
    Low iron stores increase gastrointestinal cadmium absorption via shared
    divalent metal transporter 1 (DMT1). Iron-deficient individuals, often
    women and children, are at higher risk of cadmium accumulation from dietary
    sources.
  evidence:
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The study also found that low iron stores exacerbate cadmium poisoning."
    explanation: "Systematic review confirms that iron deficiency exacerbates cadmium toxicity."
histopathology:
- name: Diffuse Alveolar Damage
  description: >-
    In acute cadmium inhalation, the lungs show diffuse alveolar damage with
    hyaline membrane formation, alveolar edema, and type II pneumocyte
    hyperplasia. This is the histopathological correlate of the acute
    respiratory distress syndrome seen clinically.
  context: Acute cadmium inhalation
  finding_term:
    preferred_term: Widespread Alveolar Pneumocyte Damage
    term:
      id: NCIT:C96237
      label: Widespread Alveolar Pneumocyte Damage Present
  evidence:
  - reference: PMID:22349354
    reference_title: "An investigation and pathological analysis of two fatal cases of cadmium poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In both cases, multiple organ damage was observed, involving brain, lung, liver, kidney, red blood cells, and platelets"
    explanation: "Autopsy of two fatal cadmium poisoning cases confirmed lung involvement as part of multi-organ pathological damage."
  - reference: PMID:16933734
    reference_title: "Acute lung injury due to cadmium inhalation--a case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Heavy metal inhalation is a rare cause of acute lung injury. Among the various heavy metals, cadmium is more commonly known to cause acute lung injury."
    explanation: "Case report of fatal cadmium inhalation with acute lung injury, the clinical manifestation of diffuse alveolar damage."
- name: Renal Tubulointerstitial Disease and Fibrosis
  description: >-
    The kidneys show proximal tubular cell necrosis with loss of brush border,
    tubulointerstitial inflammatory infiltrates, and progressive fibrosis.
    Cadmium accumulates in the renal cortex. Both cadmium and lead
    nephropathies are characterized by tubulointerstitial disease and fibrosis,
    though only early lead nephropathy shows nuclear inclusion bodies.
  finding_term:
    preferred_term: Fibrosis
    term:
      id: NCIT:C3044
      label: Fibrosis
  evidence:
  - reference: PMID:22349354
    reference_title: "An investigation and pathological analysis of two fatal cases of cadmium poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In both cases, multiple organ damage was observed, involving brain, lung, liver, kidney, red blood cells, and platelets"
    explanation: "Autopsy findings confirm kidney as a major target organ in fatal cadmium poisoning."
  - reference: PMID:19106433
    reference_title: "Nephrotoxicity of cadmium & lead."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "both entities are characterized by tubulointerstitial disease and fibrosis, but only early lead nephropathy is characterized by the presence of proximal tubule nuclear inclusion bodies, due to the combination of lead with a lead binding-protein."
    explanation: "Review confirms tubulointerstitial disease and fibrosis as the characteristic renal histopathology of cadmium nephropathy, and distinguishes it from lead nephropathy by the absence of nuclear inclusion bodies."
- name: Hepatocellular Degeneration
  description: >-
    Liver pathology shows hepatocellular degeneration and necrosis with gross
    cadmium excess on tissue analysis. Cadmium accumulates in hepatocytes
    where it is initially bound to metallothionein; when this binding capacity
    is overwhelmed, free cadmium causes oxidative damage and cell death.
  finding_term:
    preferred_term: Degeneration and Necrosis
    term:
      id: NCIT:C120875
      label: Degeneration and Necrosis
  evidence:
  - reference: PMID:22349354
    reference_title: "An investigation and pathological analysis of two fatal cases of cadmium poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In both cases, multiple organ damage was observed, involving brain, lung, liver, kidney, red blood cells, and platelets"
    explanation: "Autopsy confirmed liver involvement as part of multi-organ cadmium damage."
  - reference: PMID:7426480
    reference_title: "Cadmium-induced osteomalacia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Examination of the liver both in life and after death showed a gross excess of cadmium. This was also found in the kidneys after death."
    explanation: "Liver biopsy and postmortem analysis confirmed gross cadmium accumulation in hepatic tissue."
  - reference: PMID:41412331
    reference_title: "Diverse impacts of cadmium exposure on adolescent liver health: Suppression of steatosis and promotion of fibrosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cadmium exposure affects liver health by inhibiting steatosis and promoting fibrosis, with renal and lipid metabolism factors acting as mediators, and diet influencing the outcomes."
    explanation: "NHANES cross-sectional study in adolescents demonstrates cadmium exposure promotes hepatic fibrosis, providing human epidemiological evidence for cadmium-induced hepatocellular damage."
- name: Osteomalacic Bone Changes
  description: >-
    Bone biopsy shows widened osteoid seams with defective mineralization,
    consistent with osteomalacia. In severe cases (itai-itai disease),
    vertebral bodies show structural changes from gross deformity. Bone
    biopsies are essential for confirming the diagnosis of osteomalacia
    in cadmium-exposed patients.
  evidence:
  - reference: PMID:7426480
    reference_title: "Cadmium-induced osteomalacia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Several bone biopsies and detailed metabolic studies showed typical severe osteomalacia"
    explanation: "Multiple bone biopsies in a cadmium-exposed worker confirmed typical severe osteomalacia on histological examination."
  - reference: PMID:7426480
    reference_title: "Cadmium-induced osteomalacia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Previously unreported changes were present in the bones, especially the lumbar vertebrae which were probably more the result of gross bone deformity than cadmium deposition."
    explanation: "Histopathological examination revealed novel structural changes in vertebral bone, attributed to mechanical deformity from osteomalacia rather than direct cadmium deposition."
- name: Intracellular Dense Lysosomal Particles
  description: >-
    Transmission electron microscopy reveals a large number of dense lysosomal
    and phagocytic particles in the cytoplasm near the nucleus. This
    ultrastructural finding is observed across multiple organs and suggests
    intracellular cadmium sequestration in lysosomes, with potential
    genotoxic implications from proximity to the nucleus.
  evidence:
  - reference: PMID:22349354
    reference_title: "An investigation and pathological analysis of two fatal cases of cadmium poisoning."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "transmission electron microscopy revealed a large number of dense lysosomal and phagocytic particles in the cytoplasm near the nucleus, indicating the need for a genotoxic study of cadmium."
    explanation: "Ultrastructural finding on TEM showing characteristic perinuclear lysosomal cadmium accumulation, a distinctive histopathological marker of cadmium toxicity."
prevalence:
- population: Global
  notes: >-
    Cadmium poisoning is rare in the general population but occurs in
    occupational settings (silver industry, smelting, battery manufacturing)
    and in regions with environmental contamination. Itai-itai disease is
    endemic in cadmium-polluted areas of Japan. The condition primarily
    affects adult males through occupational exposure.
  evidence:
  - reference: PMID:41000307
    reference_title: "Clinical characteristics, management, and outcomes of cadmium poisoning: a systematic review of case reports and case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This review emphasizes that cadmium poisoning is rare and complex, with non- specific symptoms and a tendency to cause organ damage."
    explanation: "Systematic review confirms cadmium poisoning is rare overall."
differential_diagnoses:
- name: Lead Poisoning
  description: >-
    Lead poisoning shares features with cadmium toxicity including renal tubular
    dysfunction, peripheral neuropathy, and occupational exposure in metalworking
    industries. However, lead poisoning characteristically produces basophilic
    stippling of erythrocytes, a lead line on gingiva, wrist/foot drop, and
    abdominal colic, which are not features of cadmium toxicity.
  disease_term:
    preferred_term: lead poisoning
    term:
      id: MONDO:0018019
      label: lead poisoning
  distinguishing_features:
  - Basophilic stippling of erythrocytes on blood smear
  - Lead line on gingiva (Burton line)
  - Wrist drop and foot drop from motor neuropathy (cadmium causes sensory neuropathy)
  - Abdominal colic (lead colic) is characteristic
  - Elevated blood lead levels rather than blood cadmium
  - Osteomalacia and severe phosphate wasting are not typical of lead poisoning
  evidence:
  - reference: PMID:19106433
    reference_title: "Nephrotoxicity of cadmium & lead."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cadmium in sufficient cumulative dosage leads to the production of the Fanconi syndrome, a generalized proximal tubular reabsorptive defect thought to be related to inhibition of both ATP production and Na-K-ATPase activity. On the other hand, lead accumulation in the proximal tubule leads to hyperuricaemia and gout"
    explanation: "Directly contrasts cadmium vs lead nephrotoxicity, showing both settle in proximal tubule but produce different clinical manifestations."
  - reference: PMID:19106433
    reference_title: "Nephrotoxicity of cadmium & lead."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Beta2-microglobulinuria is not found in lead nephropathy."
    explanation: "Key distinguishing feature: beta-2-microglobulinuria is a hallmark of cadmium nephrotoxicity but absent in lead nephropathy."
- name: Other Causes of Acquired Fanconi Syndrome
  description: >-
    Acquired Fanconi syndrome can result from multiple causes beyond cadmium,
    including medications (tenofovir, ifosfamide, cisplatin, valproic acid),
    multiple myeloma with light chain deposition, and Wilson disease. The
    clinical presentation of proximal tubular dysfunction with LMW proteinuria,
    glucosuria, and aminoaciduria is identical regardless of cause.
  disease_term:
    preferred_term: acquired Fanconi syndrome
    term:
      id: MONDO:0060779
      label: acquired Fanconi syndrome
  distinguishing_features:
  - Medication history (tenofovir, cisplatin, ifosfamide) may explain tubular dysfunction
  - Multiple myeloma presents with monoclonal protein on serum/urine electrophoresis
  - Wilson disease shows low ceruloplasmin, elevated urine copper, and Kayser-Fleischer rings
  - Cadmium toxicity is distinguished by elevated blood/urine cadmium levels and occupational or environmental exposure history
  evidence:
  - reference: PMID:23800513
    reference_title: "Ailing bones and failing kidneys: a case of chronic cadmium toxicity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "He was finally diagnosed with chronic cadmium toxicity resulting from long-term occupational exposure."
    explanation: "Case illustrates how Fanconi syndrome presentation required occupational history and cadmium testing to distinguish from other causes."
- name: Vitamin D Deficiency Osteomalacia
  description: >-
    Nutritional vitamin D deficiency causes osteomalacia with bone pain,
    proximal myopathy, and pathologic fractures that closely mimic cadmium-
    induced osteomalacia. Both conditions present with low serum phosphate
    and elevated alkaline phosphatase.
  disease_term:
    preferred_term: vitamin D deficiency
    term:
      id: MONDO:0100471
      label: vitamin D deficiency
  distinguishing_features:
  - Low serum 25-hydroxyvitamin D level (< 20 ng/mL)
  - No renal tubular dysfunction or LMW proteinuria
  - Normal urinary cadmium levels
  - Responds to vitamin D supplementation alone without phosphate replacement
  - No occupational heavy metal exposure history
  evidence:
  - reference: PMID:31974582
    reference_title: "Hypophosphataemic osteomalacia due to cadmium exposure in the silver industry."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It is essential to maintain a high index of suspicion in diagnosing this condition. A thorough knowledge of the occupational background of patients, as well as ambient conditions at the workplace is of utmost importance in contemplating the possibility of such rare occurrences."
    explanation: "Emphasizes the need for occupational history to distinguish cadmium-induced osteomalacia from more common nutritional causes."
  - reference: PMID:7426480
    reference_title: "Cadmium-induced osteomalacia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The mechanism of development of the severe acquired Fanconi syndrome was thought to be a combination of dietary calcium and vitamin D deficiency and impaired calcium absorption from abnormal vitamin D synthesis, related to the cadmium deposition in the renal tubules"
    explanation: "Demonstrates that cadmium-induced osteomalacia involves impaired renal vitamin D synthesis, making it difficult to distinguish from pure nutritional vitamin D deficiency without cadmium testing."
- name: Metal Fume Fever
  description: >-
    Metal fume fever, typically caused by zinc oxide fume inhalation, presents
    with flu-like symptoms (fever, myalgias, metallic taste) hours after
    welding or metalworking. It mimics early acute cadmium inhalation but
    is self-limiting within 24-48 hours and does not progress to ARDS.
  distinguishing_features:
  - Self-limiting course resolving within 24-48 hours
  - Does not progress to ARDS or respiratory failure
  - Typically caused by zinc rather than cadmium fumes
  - No renal or skeletal toxicity
  - Cadmium fume exposure causes delayed-onset (12-36 hours) progressive respiratory failure
  evidence:
  - reference: PMID:16933734
    reference_title: "Acute lung injury due to cadmium inhalation--a case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Heavy metal inhalation is a rare cause of acute lung injury. Among the various heavy metals, cadmium is more commonly known to cause acute lung injury."
    explanation: "Cadmium fume inhalation causes true acute lung injury, unlike the benign self-limiting course of metal fume fever."
- name: X-linked Hypophosphatemia
  description: >-
    X-linked hypophosphatemia (XLH) is an inherited disorder of renal phosphate
    wasting caused by PHEX gene mutations, leading to excess FGF23 and
    hypophosphataemic rickets/osteomalacia. It presents with similar phosphate
    wasting and skeletal findings but occurs from childhood without heavy metal
    exposure.
  disease_term:
    preferred_term: X-linked hypophosphatemic rickets
    term:
      id: MONDO:0020720
      label: X-linked hypophosphatemic rickets
  distinguishing_features:
  - Childhood onset with rickets, short stature, and bowing of lower limbs
  - Family history consistent with X-linked dominant inheritance
  - Elevated FGF23 levels
  - No LMW proteinuria or generalized Fanconi syndrome
  - Normal cadmium levels
  - No occupational or environmental exposure history
  evidence:
  - reference: PMID:31974582
    reference_title: "Hypophosphataemic osteomalacia due to cadmium exposure in the silver industry."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Three silversmiths presented similarly with clinical, biochemical and radiological evidence of hypophosphataemic osteomalacia."
    explanation: "Adult-onset hypophosphataemic osteomalacia from cadmium exposure contrasts with XLH, which presents in childhood; cadmium-induced phosphate wasting is acquired and accompanied by Fanconi syndrome."
clinical_trials:
- name: NCT05908383
  phase: PHASE_I
  status: COMPLETED
  description: >-
    Phase I, randomized, double-blind, single-center, single-dose escalation
    trial evaluating the safety, tolerability, and pharmacokinetic characteristics
    of injectable GMDTC (a novel cadmium chelation agent) in healthy subjects.
    This is the foundational safety study for the GMDTC cadmium chelation program.
  evidence:
  - reference: clinicaltrials:NCT05908383
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This trial is a randomized, double-blind, single-center, single-dose escalating Phase I clinical trial designed to evaluate the safety, tolerability, and pharmacokinetic characteristics of injectable GMDTC in healthy subjects"
    explanation: "First-in-human safety trial for GMDTC, a novel chelation agent being developed specifically for cadmium poisoning."
- name: NCT06199349
  phase: PHASE_I
  status: COMPLETED
  description: >-
    Phase Ib trial evaluating the safety, tolerability, and pharmacokinetic
    characteristics of repeated-dose GMDTC injection in people with excessive
    cadmium levels. This trial extends the Phase I safety profile from healthy
    volunteers to the target population of cadmium-exposed individuals across
    three dose cohorts.
  target_phenotypes:
  - preferred_term: Chronic kidney disease
    term:
      id: HP:0012622
      label: Chronic kidney disease
  evidence:
  - reference: clinicaltrials:NCT06199349
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This trial is a randomized, double-blind, single-center, single-dose escalating Phase I clinical trial designed to evaluate the safety, tolerability, and pharmacokinetic characteristics of GMDTC for injection after repeated administration in people with excessive cadmium levels."
    explanation: "First trial of GMDTC chelation directly in cadmium-exposed individuals, establishing repeated-dose safety and pharmacokinetics in the target population."
- name: NCT07057414
  phase: PHASE_II
  status: RECRUITING
  description: >-
    Phase IIa, randomized, double-blind, placebo-controlled trial evaluating
    the safety and efficacy of GMDTC injection in subjects with elevated cadmium
    levels. This is the first controlled efficacy trial of a chelation agent
    specifically developed for cadmium poisoning.
  target_phenotypes:
  - preferred_term: Chronic kidney disease
    term:
      id: HP:0012622
      label: Chronic kidney disease
  evidence:
  - reference: clinicaltrials:NCT07057414
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This is a randomized, double-blind, placebo-controlled, single-center Phase IIa clinical study."
    explanation: "First placebo-controlled efficacy trial for cadmium-specific chelation therapy, representing a significant advance given that no approved treatment exists for cadmium poisoning."
- name: NCT00376987
  phase: PHASE_II
  status: COMPLETED
  description: >-
    Clinical trial evaluating whether dietary zinc supplements can reduce serum
    cadmium levels in current cigarette smokers. Leverages the known competitive
    interaction between zinc and cadmium at shared divalent metal transporters
    (DMT1) to potentially reduce cadmium body burden through a simple dietary
    intervention.
  target_phenotypes:
  - preferred_term: Proteinuria
    term:
      id: HP:0000093
      label: Proteinuria
  evidence:
  - reference: clinicaltrials:NCT00376987
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Zinc supplements may lower cadmium levels in smokers and may help prevent DNA damage."
    explanation: "Evaluates a non-chelation approach to reducing cadmium burden by exploiting zinc-cadmium competition at shared intestinal transporters."
datasets:
- accession: geo:GSE198150
  title: The protease DDI2 regulates NRF1-metallothionein pathway in response to Cadmium toxicity in the liver
  description: >-
    RNA-seq profiling of liver tissue from liver-specific Ddi2 knockout and
    wild-type mice, investigating how the protease DDI2 regulates the
    NRF1-metallothionein pathway in response to cadmium toxicity. Identifies
    DDI2-mediated metallothionein activation as a protective mechanism against
    cadmium-induced hepatotoxicity.
  organism:
    preferred_term: mouse
    term:
      id: NCBITaxon:10090
      label: Mus musculus
  data_type: BULK_RNA_SEQ
  sample_types:
  - preferred_term: liver tissue
    tissue_term:
      preferred_term: liver
      term:
        id: UBERON:0002107
        label: liver
  sample_count: 4
  conditions:
  - Ddi2 liver-specific knockout
  - wild-type control
  platform: Illumina HiSeq 2500
  publication: PMID:36248746
  notes: >-
    2 replicates per condition (WT vs Ddi2-KO). Demonstrates that DDI2
    cleaves and activates NRF1 to drive metallothionein expression in
    response to cadmium, linking proteasome homeostasis to heavy metal
    detoxification.
references:
- reference: DOI:10.1038/s41598-022-27292-7
  title: Association between levels of exposure to heavy metals and renal function indicators of residents in environmentally vulnerable areas
  found_in:
  - Cadmium_Poisoning-deep-research-falcon.md
  findings:
  - statement: Abandoned metal mines and refineries are considered environmentally vulnerable areas owing to high levels of exposure to heavy metals.
    supporting_text: Abandoned metal mines and refineries are considered environmentally vulnerable areas owing to high levels of exposure to heavy metals.
    evidence:
    - reference: DOI:10.1038/s41598-022-27292-7
      reference_title: Association between levels of exposure to heavy metals and renal function indicators of residents in environmentally vulnerable areas
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Abandoned metal mines and refineries are considered environmentally vulnerable areas owing to high levels of exposure to heavy metals.
      explanation: Deep research cited this publication as relevant literature for Cadmium Poisoning.
- reference: DOI:10.1038/s41598-023-28968-4
  title: Combating lead and cadmium exposure with an orally administered chitosan-based chelating polymer
  found_in:
  - Cadmium_Poisoning-deep-research-falcon.md
  findings:
  - statement: Heavy metals present a threat to human health, even at minimal concentrations within the body.
    supporting_text: Heavy metals present a threat to human health, even at minimal concentrations within the body.
    evidence:
    - reference: DOI:10.1038/s41598-023-28968-4
      reference_title: Combating lead and cadmium exposure with an orally administered chitosan-based chelating polymer
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Heavy metals present a threat to human health, even at minimal concentrations within the body.
      explanation: Deep research cited this publication as relevant literature for Cadmium Poisoning.
- reference: DOI:10.1038/s41598-024-63858-3
  title: Associations of mixed metal exposure with chronic kidney disease from NHANES 2011–2018
  found_in:
  - Cadmium_Poisoning-deep-research-falcon.md
  findings:
  - statement: Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear.
    supporting_text: Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear.
    evidence:
    - reference: DOI:10.1038/s41598-024-63858-3
      reference_title: Associations of mixed metal exposure with chronic kidney disease from NHANES 2011–2018
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear.
      explanation: Deep research cited this publication as relevant literature for Cadmium Poisoning.
- reference: DOI:10.20944/preprints202604.0484.v1
  title: Are the Guidelines for Dietary and Workplace Exposure to Cadmium Adequate?
  found_in:
  - Cadmium_Poisoning-deep-research-falcon.md
  findings:
  - statement: Cadmium (Cd) is a heavy metal pollutant to which most people are exposed daily through their diet.
    supporting_text: Cadmium (Cd) is a heavy metal pollutant to which most people are exposed daily through their diet.
    evidence:
    - reference: DOI:10.20944/preprints202604.0484.v1
      reference_title: Are the Guidelines for Dietary and Workplace Exposure to Cadmium Adequate?
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Cadmium (Cd) is a heavy metal pollutant to which most people are exposed daily through their diet.
      explanation: Deep research cited this publication as relevant literature for Cadmium Poisoning.
- reference: DOI:10.3389/fpubh.2023.1146263
  title: 'National analysis of urinary cadmium concentration and kidney stone: Evidence from NHANES (2011–2020)'
  found_in:
  - Cadmium_Poisoning-deep-research-falcon.md
  findings:
  - statement: The association between urinary cadmium and kidney stone risk is inconsistent in previous studies, which needs further exploration.
    supporting_text: The association between urinary cadmium and kidney stone risk is inconsistent in previous studies, which needs further exploration.
    evidence:
    - reference: DOI:10.3389/fpubh.2023.1146263
      reference_title: 'National analysis of urinary cadmium concentration and kidney stone: Evidence from NHANES (2011–2020)'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: The association between urinary cadmium and kidney stone risk is inconsistent in previous studies, which needs further exploration.
      explanation: Deep research cited this publication as relevant literature for Cadmium Poisoning.
- reference: DOI:10.3390/biom15081083
  title: 'Metallothionein and Other Factors Influencing Cadmium-Induced Kidney Dysfunction: Review and Commentary'
  found_in:
  - Cadmium_Poisoning-deep-research-falcon.md
  findings:
  - statement: Cadmium is widely recognized as an important environmental toxicant that may give rise to kidney dysfunction, bone disease, and cancer in humans and animals.
    supporting_text: Cadmium is widely recognized as an important environmental toxicant that may give rise to kidney dysfunction, bone disease, and cancer in humans and animals.
    evidence:
    - reference: DOI:10.3390/biom15081083
      reference_title: 'Metallothionein and Other Factors Influencing Cadmium-Induced Kidney Dysfunction: Review and Commentary'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Cadmium is widely recognized as an important environmental toxicant that may give rise to kidney dysfunction, bone disease, and cancer in humans and animals.
      explanation: Deep research cited this publication as relevant literature for Cadmium Poisoning.
- reference: DOI:10.3390/ijms27083513
  title: 'Heavy Metal Toxicity in Clinical and Environmental Health: Sources, Mechanisms, Diagnostics, and Evidence-Based Management of Mercury, Lead, Cadmium, and Arsenic'
  found_in:
  - Cadmium_Poisoning-deep-research-falcon.md
  findings:
  - statement: Heavy metals including mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) remain significant global toxins due to their environmental persistence, widespread anthropogenic release, and serious biological effects.
    supporting_text: Heavy metals including mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) remain significant global toxins due to their environmental persistence, widespread anthropogenic release, and serious biological effects.
    evidence:
    - reference: DOI:10.3390/ijms27083513
      reference_title: 'Heavy Metal Toxicity in Clinical and Environmental Health: Sources, Mechanisms, Diagnostics, and Evidence-Based Management of Mercury, Lead, Cadmium, and Arsenic'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Heavy metals including mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) remain significant global toxins due to their environmental persistence, widespread anthropogenic release, and serious biological effects.
      explanation: Deep research cited this publication as relevant literature for Cadmium Poisoning.
- reference: DOI:10.3390/jox15040122
  title: 'Hypertension in People Exposed to Environmental Cadmium: Roles for 20-Hydroxyeicosatetraenoic Acid in the Kidney'
  found_in:
  - Cadmium_Poisoning-deep-research-falcon.md
  findings:
  - statement: Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension.
    supporting_text: Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension.
    evidence:
    - reference: DOI:10.3390/jox15040122
      reference_title: 'Hypertension in People Exposed to Environmental Cadmium: Roles for 20-Hydroxyeicosatetraenoic Acid in the Kidney'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension.
      explanation: Deep research cited this publication as relevant literature for Cadmium Poisoning.
- reference: DOI:10.3390/toxics12110775
  title: Urinary N-acetylglucosaminidase in People Environmentally Exposed to Cadmium Is Minimally Related to Cadmium-Induced Nephron Destruction
  found_in:
  - Cadmium_Poisoning-deep-research-falcon.md
  findings:
  - statement: Exposure to even low levels of the environmental pollutant cadmium (Cd) increases the risk of kidney damage and malfunction.
    supporting_text: Exposure to even low levels of the environmental pollutant cadmium (Cd) increases the risk of kidney damage and malfunction.
    evidence:
    - reference: DOI:10.3390/toxics12110775
      reference_title: Urinary N-acetylglucosaminidase in People Environmentally Exposed to Cadmium Is Minimally Related to Cadmium-Induced Nephron Destruction
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Exposure to even low levels of the environmental pollutant cadmium (Cd) increases the risk of kidney damage and malfunction.
      explanation: Deep research cited this publication as relevant literature for Cadmium Poisoning.
📚

References & Deep Research

References

9
DOI:10.1038/s41598-022-27292-7
Association between levels of exposure to heavy metals and renal function indicators of residents in environmentally vulnerable areas
1 finding
Abandoned metal mines and refineries are considered environmentally vulnerable areas owing to high levels of exposure to heavy metals.
"Abandoned metal mines and refineries are considered environmentally vulnerable areas owing to high levels of exposure to heavy metals."
Show evidence (1 reference)
DOI:10.1038/s41598-022-27292-7 SUPPORT Human Clinical
"Abandoned metal mines and refineries are considered environmentally vulnerable areas owing to high levels of exposure to heavy metals."
Deep research cited this publication as relevant literature for Cadmium Poisoning.
DOI:10.1038/s41598-023-28968-4
Combating lead and cadmium exposure with an orally administered chitosan-based chelating polymer
1 finding
Heavy metals present a threat to human health, even at minimal concentrations within the body.
"Heavy metals present a threat to human health, even at minimal concentrations within the body."
Show evidence (1 reference)
DOI:10.1038/s41598-023-28968-4 SUPPORT Human Clinical
"Heavy metals present a threat to human health, even at minimal concentrations within the body."
Deep research cited this publication as relevant literature for Cadmium Poisoning.
DOI:10.1038/s41598-024-63858-3
Associations of mixed metal exposure with chronic kidney disease from NHANES 2011–2018
1 finding
Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear.
"Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear."
Show evidence (1 reference)
DOI:10.1038/s41598-024-63858-3 SUPPORT Human Clinical
"Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear."
Deep research cited this publication as relevant literature for Cadmium Poisoning.
DOI:10.20944/preprints202604.0484.v1
Are the Guidelines for Dietary and Workplace Exposure to Cadmium Adequate?
1 finding
Cadmium (Cd) is a heavy metal pollutant to which most people are exposed daily through their diet.
"Cadmium (Cd) is a heavy metal pollutant to which most people are exposed daily through their diet."
Show evidence (1 reference)
DOI:10.20944/preprints202604.0484.v1 SUPPORT Other
"Cadmium (Cd) is a heavy metal pollutant to which most people are exposed daily through their diet."
Deep research cited this publication as relevant literature for Cadmium Poisoning.
DOI:10.3389/fpubh.2023.1146263
National analysis of urinary cadmium concentration and kidney stone: Evidence from NHANES (2011–2020)
1 finding
The association between urinary cadmium and kidney stone risk is inconsistent in previous studies, which needs further exploration.
"The association between urinary cadmium and kidney stone risk is inconsistent in previous studies, which needs further exploration."
Show evidence (1 reference)
DOI:10.3389/fpubh.2023.1146263 SUPPORT Human Clinical
"The association between urinary cadmium and kidney stone risk is inconsistent in previous studies, which needs further exploration."
Deep research cited this publication as relevant literature for Cadmium Poisoning.
DOI:10.3390/biom15081083
Metallothionein and Other Factors Influencing Cadmium-Induced Kidney Dysfunction: Review and Commentary
1 finding
Cadmium is widely recognized as an important environmental toxicant that may give rise to kidney dysfunction, bone disease, and cancer in humans and animals.
"Cadmium is widely recognized as an important environmental toxicant that may give rise to kidney dysfunction, bone disease, and cancer in humans and animals."
Show evidence (1 reference)
DOI:10.3390/biom15081083 SUPPORT Human Clinical
"Cadmium is widely recognized as an important environmental toxicant that may give rise to kidney dysfunction, bone disease, and cancer in humans and animals."
Deep research cited this publication as relevant literature for Cadmium Poisoning.
DOI:10.3390/ijms27083513
Heavy Metal Toxicity in Clinical and Environmental Health: Sources, Mechanisms, Diagnostics, and Evidence-Based Management of Mercury, Lead, Cadmium, and Arsenic
1 finding
Heavy metals including mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) remain significant global toxins due to their environmental persistence, widespread anthropogenic release, and serious biological effects.
"Heavy metals including mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) remain significant global toxins due to their environmental persistence, widespread anthropogenic release, and serious biological effects."
Show evidence (1 reference)
DOI:10.3390/ijms27083513 SUPPORT Human Clinical
"Heavy metals including mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) remain significant global toxins due to their environmental persistence, widespread anthropogenic release, and serious biological effects."
Deep research cited this publication as relevant literature for Cadmium Poisoning.
DOI:10.3390/jox15040122
Hypertension in People Exposed to Environmental Cadmium: Roles for 20-Hydroxyeicosatetraenoic Acid in the Kidney
1 finding
Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension.
"Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension."
Show evidence (1 reference)
DOI:10.3390/jox15040122 SUPPORT Human Clinical
"Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension."
Deep research cited this publication as relevant literature for Cadmium Poisoning.
DOI:10.3390/toxics12110775
Urinary N-acetylglucosaminidase in People Environmentally Exposed to Cadmium Is Minimally Related to Cadmium-Induced Nephron Destruction
1 finding
Exposure to even low levels of the environmental pollutant cadmium (Cd) increases the risk of kidney damage and malfunction.
"Exposure to even low levels of the environmental pollutant cadmium (Cd) increases the risk of kidney damage and malfunction."
Show evidence (1 reference)
DOI:10.3390/toxics12110775 SUPPORT Human Clinical
"Exposure to even low levels of the environmental pollutant cadmium (Cd) increases the risk of kidney damage and malfunction."
Deep research cited this publication as relevant literature for Cadmium Poisoning.

Deep Research

1
Falcon ▸
Disease Characteristics Research Template
Edison Scientific Literature 52 citations 2026-05-08T10:48:48.109207

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

  • Disease Name: Cadmium Poisoning
  • MONDO ID: (if available)
  • Category: Environmental

Research Objectives

Please provide a comprehensive research report on Cadmium Poisoning covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

  • What is the disease? Provide a concise overview.
  • What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
  • What are the common synonyms and alternative names?
  • Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

  • Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
  • Risk Factors:

    Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases

  • Genetic risk factors (causal variants, susceptibility loci, modifier genes)
  • Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
  • Protective Factors:

    Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases

  • Genetic protective factors (protective variants, modifier alleles)
  • Environmental protective factors (diet, lifestyle, exposures that reduce risk)
  • Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

    Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

  • Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

    Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene

  • Pathogenic Variants:
  • Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
  • Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
  • Variant type/class (missense, frameshift, nonsense, splice-site, structural)
  • Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
  • Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
  • Functional consequences (loss of function, gain of function, dominant negative)
  • Modifier Genes: Genes that modify disease severity or expression
  • Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

    Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

  • Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

    Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases

  • Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

    Search first: CDC databases, WHO, PubMed, NHANES

  • Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

    Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

  • Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

    Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc

  • Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

    Search first: Gene Ontology (GO), Reactome, KEGG, PubMed

  • Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

    Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold

  • Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

    Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA

  • Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

    Search first: ImmPort, Immunome Database, IEDB, Gene Ontology

  • Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

    Search first: PubMed, Gene Ontology, Reactome

  • Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

    Search first: BRENDA, UniProt, KEGG, OMIM, PubMed

  • Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Molecular Profiling (if available):
  • Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
  • Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
  • Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
  • Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
  • Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
  • Advanced Technologies (if applicable):
  • Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
  • Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
  • Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
  • Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

  • Organ Level:
  • Primary organs directly affected
  • Secondary organ involvement (complications, secondary effects)
  • Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

    Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT

  • Tissue and Cell Level:
  • Specific tissue types affected (epithelial, connective, muscle, nervous)
  • Specific cell populations targeted (with Cell Ontology terms)

    Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB

  • Subcellular Level:
  • Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

    Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas

  • Localization:
  • Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
  • Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

  • Onset:
  • Typical age of onset (congenital, pediatric, adult, geriatric)
  • Onset pattern (acute, subacute, chronic, insidious)

    Search first: OMIM, Orphanet, HPO, PubMed

  • Progression:
  • Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
  • Progression rate (rapid, slow, variable)
  • Disease course pattern (episodic, relapsing-remitting, progressive, stable)
  • Disease duration (self-limited, chronic lifelong)

    Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM

  • Patterns:
  • Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
  • Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

  • Epidemiology:
  • Prevalence (cases per 100,000 at given time)
  • Incidence (new cases per 100,000 per year)

    Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries

  • For Genetic Etiology:
  • Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
  • Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
  • Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
  • Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
  • Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
  • Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
  • Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
  • Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
  • Population Demographics:
  • Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
  • Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
  • Geographic distribution of specific variants
  • Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
  • Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

  • Clinical Tests:
  • Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
  • Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
  • Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
  • Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
  • Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
  • Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
  • Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
  • Genetic Testing:

    Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen

  • Overview of recommended genetic testing approach
  • Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
  • Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
  • Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
  • Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
  • Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
  • Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
  • FISH > Search first: ClinVar, cytogenetics databases, PubMed
  • Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
  • Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
  • Omics-Based Diagnostics (if applicable):
  • RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
  • Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
  • Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
  • Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
  • Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
  • Clinical Criteria:
  • Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
  • Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
  • Screening:
  • Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

  • Survival and Mortality:
  • Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
  • Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
  • Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
  • Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
  • Morbidity and Function:
  • Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
  • Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
  • Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
  • Disease Course:
  • Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
  • Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
  • Prediction:
  • Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
  • Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

  • Pharmacotherapy:
  • Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
  • Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
  • Advanced Therapeutics:
  • Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
  • Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
  • RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
  • Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
  • Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
  • Surgical and Interventional:
  • Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
  • Supportive and Rehabilitative:
  • Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
  • Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
  • Experimental:
  • Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
  • Treatment Outcomes:
  • Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
  • Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
  • Treatment Strategy:
  • Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
  • Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
  • Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

  • Prevention Levels:
  • Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
  • Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
  • Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
  • Immunization: Vaccine strategies (if applicable)

    Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database

  • Screening and Early Detection:
  • Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
  • Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
  • Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
  • Behavioral Interventions: Lifestyle modifications to reduce risk

    Search first: CDC, WHO, behavioral intervention databases, Cochrane Library

  • Counseling: Genetic counseling (risk assessment, family planning guidance)

    Search first: NSGC resources, ACMG guidelines, GeneReviews

  • Public Health:
  • Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
  • Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
  • Prophylaxis: Preventive medications or procedures

    Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

  • Taxonomy: Species affected (with NCBI Taxon identifiers)

    Search first: NCBI Taxonomy

  • Breed: Specific breeds affected (with VBO identifiers if applicable)

    Search first: VBO (Vertebrate Breed Ontology)

  • Gene: Orthologous genes in other species (with NCBI Gene IDs)

    Search first: NCBI Gene

  • Natural Disease:
  • Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
  • Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
  • Comparative Biology:
  • Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
  • Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
  • Transmission (if applicable):
  • Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
  • Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

  • Model Types:
  • Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
  • Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
  • Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
  • Genetic Models:
  • Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
  • Model Characteristics:
  • Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
  • Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
  • Applications:
  • Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
  • Resources:
  • Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

  • Cite primary literature (PMID preferred) for all mechanistic and clinical claims
  • Prioritize recent reviews and landmark papers
  • Include direct quotes from abstracts where possible to support key statements
  • Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Cadmium Poisoning (Cadmium Toxicity): Comprehensive Disease Characteristics Report (Environmental)

1. Disease Information

Cadmium poisoning (also termed cadmium toxicity or cadmium intoxication) is an exposure-mediated toxicologic disorder caused by acute high-dose cadmium (Cd) exposure (often inhalational) or chronic low-to-moderate exposure with long-term bioaccumulation, particularly in the kidney cortex. Acute disease is often dominated by pulmonary injury, while chronic disease is dominated by renal tubular injury with downstream effects on bone and other systems. (balalimood2025recentadvancesin pages 9-11, chakif2026heavymetaltoxicity pages 12-13)

Key identifiers (ontology/classification): MONDO, MeSH, ICD-10/ICD-11 identifiers were not retrievable from the tool evidence in this run and therefore are not reported here to avoid fabrication. (artifact-00)

Common synonyms/alternative names: cadmium toxicity; cadmium intoxication; chronic cadmium exposure toxicity; cadmium-induced nephrotoxicity (subset). (vamsi2024cadmiumtoxicityunveiling pages 8-9, balalimood2025recentadvancesin pages 9-11)

Evidence sources: The retrieved evidence base is primarily aggregated disease-level resources (reviews) and population/cohort studies (NHANES, regional cohorts), not EHR-derived phenotyping. (balalimood2025recentadvancesin pages 9-11, shi2024associationsofmixed pages 1-2)

Concept item Details Evidence/notes Key sources (URL; year)
Disease name Cadmium poisoning Environmental/toxic exposure disorder caused by acute or chronic exposure to cadmium or cadmium compounds. Acute disease is dominated by inhalational or high-dose ingestion toxicity; chronic disease reflects bioaccumulation, especially in kidney cortex. (balalimood2025recentadvancesin pages 9-11, chakif2026heavymetaltoxicity pages 12-13) Balali-Mood et al., Heliyon, https://doi.org/10.1016/j.heliyon.2025.e42696; 2025. Chakif & Furrer, Int J Mol Sci, https://doi.org/10.3390/ijms27083513; 2026.
Core alternative names Cadmium toxicity; cadmium intoxication; cadmium exposure toxicity Recent reviews use these terms interchangeably in clinical/environmental toxicology contexts rather than as distinct diseases. (balalimood2025recentadvancesin pages 11-12, vamsi2024cadmiumtoxicityunveiling pages 8-9) Balali-Mood et al., https://doi.org/10.1016/j.heliyon.2025.e42696; 2025. Vamsi et al., https://doi.org/10.36468/pharmaceutical-sciences.1427; 2024.
Disease category Environmental / toxicologic / heavy-metal poisoning Non-Mendelian, exposure-mediated condition; evidence in retrieved tools is disease-level literature and cohort/review evidence, not patient-specific EHR-derived ontology records. (balalimood2025recentadvancesin pages 9-11, chakif2026heavymetaltoxicity pages 12-13) Balali-Mood et al., https://doi.org/10.1016/j.heliyon.2025.e42696; 2025. Chakif & Furrer, https://doi.org/10.3390/ijms27083513; 2026.
MONDO ID not retrieved from tool evidence Do not infer or invent identifier. Not retrieved from ontology-focused tool evidence.
MeSH ID / descriptor ID not retrieved from tool evidence Do not infer or invent identifier. Not retrieved from ontology-focused tool evidence.
ICD-10 / ICD-11 code not retrieved from tool evidence Toxic-effect coding likely exists in classification systems, but explicit code was not retrieved from tool evidence and should not be invented here. Not retrieved from tool evidence.
Acute cadmium poisoning Usually follows inhalation of cadmium oxide fumes/dust or high-dose ingestion Defined clinically by respiratory irritation with symptom onset typically within 6–12 h after inhalation; may progress to cough, fever, respiratory distress, hypoxia, pneumonitis, pulmonary insufficiency, or death in severe cases. One review notes inhalation of 5 mg/m3 for 8 h may be lethal. (balalimood2025recentadvancesin pages 9-11, balalimood2025recentadvancesin pages 11-12, chakif2026heavymetaltoxicity pages 12-13) Balali-Mood et al., https://doi.org/10.1016/j.heliyon.2025.e42696; 2025. Chakif & Furrer, https://doi.org/10.3390/ijms27083513; 2026.
Chronic cadmium poisoning Long-term bioaccumulation disorder, especially affecting kidney, bone, lung, and cardiovascular system Cadmium has a very long biologic half-life in kidney (~20–30 years in review evidence). Hallmark chronic effects are renal proximal tubular injury, proteinuria, progressive CKD, and skeletal demineralization/osteomalacia/osteoporosis. (chakif2026heavymetaltoxicity pages 12-13, chakif2026heavymetaltoxicity pages 7-8) Chakif & Furrer, https://doi.org/10.3390/ijms27083513; 2026. Balali-Mood et al., https://doi.org/10.1016/j.heliyon.2025.e42696; 2025.
Major exposure sources Food, smoking/tobacco, occupational inhalation, contaminated air/water/soil Tobacco smoke is a major source; each cigarette may contain ~0.5–1 µg Cd. Occupational sources include mining, smelting, battery manufacture/recycling, fossil fuel combustion, plating, fertilizer production, and waste disposal. (balalimood2025recentadvancesin pages 9-11, chakif2026heavymetaltoxicity pages 7-8) Balali-Mood et al., https://doi.org/10.1016/j.heliyon.2025.e42696; 2025. Chakif & Furrer, https://doi.org/10.3390/ijms27083513; 2026.
Renal hallmark definition Cadmium nephrotoxicity with tubular and glomerular effects Chronic exposure causes often irreversible proteinuria and tubular dysfunction. Nordberg review notes albuminuria is mainly glomerular and may fall when blood Cd decreases, while tubular dysfunction markers (β2-microglobulin, NAG) appear linked to accumulated tubular Cd and seem more irreversible. (nordberg2025metallothioneinandother pages 9-11) Nordberg & Nordberg, Biomolecules, https://doi.org/10.3390/biom15081083; 2025.
Key renal biomarkers Urine Cd (body burden), blood Cd (recent/ongoing exposure), urinary β2-microglobulin, urinary NAG, urinary albumin, eGFR Reviews and cohorts repeatedly use urine Cd and blood Cd as exposure biomarkers; β2-microglobulin (B2-MG/β2-MG), NAG, and albuminuria are effect biomarkers; eGFR decline tracks clinically important renal loss. (nordberg2025metallothioneinandother pages 12-14, nordberg2025metallothioneinandother pages 9-11, chakif2026heavymetaltoxicity pages 12-13, chakif2026heavymetaltoxicity pages 14-16) Nordberg & Nordberg, https://doi.org/10.3390/biom15081083; 2025. Chakif & Furrer, https://doi.org/10.3390/ijms27083513; 2026.
β2-microglobulinuria threshold Urinary β2-microglobulin >300 µg/g creatinine (or >300 µg/L in some studies) Used in multiple studies/reviews as a threshold for cadmium-related tubular dysfunction/kidney dysfunction. Nordberg review explicitly references urinary B2M >300 µg/g creatinine; Kwon study used β2-MG >300 µg/L as reference exceedance. (nordberg2025metallothioneinandother pages 9-11, nordberg2025metallothioneinandother pages 11-12, kwon2023associationbetweenlevels pages 9-10) Nordberg & Nordberg, https://doi.org/10.3390/biom15081083; 2025. Kwon et al., https://doi.org/10.1038/s41598-022-27292-7; 2023.
NAG threshold / interpretation Urinary NAG is an early tubular injury biomarker; threshold examples vary by study Nordberg figure legend cited UNAG >23 U/g creatinine; Kwon study used NAG >11.5 U/L as reference exceedance; increased NAG is consistently linked with urinary cadmium. (nordberg2025metallothioneinandother pages 11-12, kwon2023associationbetweenlevels pages 9-10) Nordberg & Nordberg, https://doi.org/10.3390/biom15081083; 2025. Kwon et al., https://doi.org/10.1038/s41598-022-27292-7; 2023.
Urinary cadmium threshold for renal risk ~2–5 µg/g creatinine may indicate elevated body burden/renal risk; >10 µg/g creatinine associated with irreversible kidney damage in one review Chakif review states chronic renal risk may occur at lower urinary levels than older models suggested and that ~2–5 µg/g creatinine may indicate elevated burden/risk. Vamsi review states urinary Cd <10 µg/g creatinine is associated with reversible renal dysfunction, whereas >10 µg/g creatinine can cause irreversible kidney damage. (chakif2026heavymetaltoxicity pages 14-16, vamsi2024cadmiumtoxicityunveiling pages 8-9) Chakif & Furrer, https://doi.org/10.3390/ijms27083513; 2026. Vamsi et al., https://doi.org/10.36468/pharmaceutical-sciences.1427; 2024.
Metallothionein-related definition Cadmium binds metallothionein (MT); MT is central to transport, sequestration, and renal toxicity modification Nordberg review emphasizes MT as central to toxicokinetics: Cd-MT transports cadmium to renal tubules, and MT expression/protection modifies kidney injury risk. Anti-MT antibodies and low zinc status may worsen susceptibility. (nordberg2025metallothioneinandother pages 12-14, nordberg2025metallothioneinandother pages 9-11) Nordberg & Nordberg, https://doi.org/10.3390/biom15081083; 2025.
Bone disease definition Cadmium-related osteotoxicity / Itai-itai-like disease Chronic exposure is associated with low bone mineralization, decalcification, fractures, osteomalacia, and osteoporosis; classic severe manifestation is Itai-itai disease. (balalimood2025recentadvancesin pages 9-11, chakif2026heavymetaltoxicity pages 12-13) Balali-Mood et al., https://doi.org/10.1016/j.heliyon.2025.e42696; 2025. Chakif & Furrer, https://doi.org/10.3390/ijms27083513; 2026.
Lung involvement definition Acute toxic inhalation injury and chronic pulmonary toxicity Acute inhalation causes irritant pneumonitis/respiratory distress; chronic exposure has been linked to COPD/emphysema in reviews. (balalimood2025recentadvancesin pages 9-11, balalimood2025recentadvancesin pages 11-12) Balali-Mood et al., https://doi.org/10.1016/j.heliyon.2025.e42696; 2025.
Clinical management definition Source control and supportive care are first-line; chelation is limited/controversial for cadmium Reviews emphasize removing exposure, supportive care, occupational controls, smoking cessation, and nutrition. Routine chelation is not first-line; benefits are uncertain and some agents may worsen toxicity. BAL/dimercaprol is specifically discouraged/contraindicated for cadmium because Cd-BAL complexes may be more nephrotoxic. (balalimood2025recentadvancesin pages 11-12, chakif2026heavymetaltoxicity pages 16-17, chakif2026heavymetaltoxicity pages 8-9, vamsi2024cadmiumtoxicityunveiling pages 8-9) Balali-Mood et al., https://doi.org/10.1016/j.heliyon.2025.e42696; 2025. Chakif & Furrer, https://doi.org/10.3390/ijms27083513; 2026. Vamsi et al., https://doi.org/10.36468/pharmaceutical-sciences.1427; 2024.
Protective/nutritional modifiers Adequate zinc, iron, selenium, calcium may reduce cadmium uptake or toxicity Reviews cite dietary sufficiency and good zinc status as protective; Nordberg review highlights inverse associations between zinc status/Zn-Cd quotient and tubular dysfunction. (balalimood2025recentadvancesin pages 9-11, nordberg2025metallothioneinandother pages 11-12) Balali-Mood et al., https://doi.org/10.1016/j.heliyon.2025.e42696; 2025. Nordberg & Nordberg, https://doi.org/10.3390/biom15081083; 2025.

Table: This table summarizes the key identifiers, synonyms, and working clinical definitions for cadmium poisoning from the retrieved evidence base. It highlights how recent reviews define acute versus chronic toxicity and the main biomarkers and thresholds used in practice.

2. Etiology

2.1 Primary causal factors

Cadmium poisoning is primarily an environmental/occupational toxic exposure condition. Primary exposure routes include ingestion (diet), inhalation (occupational, tobacco smoke), and exposure through contaminated air/water/soil. (balalimood2025recentadvancesin pages 9-11, chakif2026heavymetaltoxicity pages 7-8)

2.2 Risk factors

Major exposure sources: - Tobacco smoking: A recent clinical review notes that “each cigarette may contain ~0.5–1 μg Cd,” highlighting tobacco smoke as a major atmospheric source. (balalimood2025recentadvancesin pages 9-11) - Occupational/industrial: mining, smelting, battery manufacture/recycling, fossil fuel combustion, plating, fertilizer production, and waste disposal are emphasized as major sources. (balalimood2025recentadvancesin pages 9-11) - Dietary exposure: Cd is widely present in foods; chronic exposure is therefore common. (satarug2025hypertensioninpeople pages 16-17)

Host susceptibility: - Iron deficiency/low iron stores can increase intestinal absorption of Cd; women and children are noted as higher-risk groups due to lower iron stores. (satarug2026aretheguidelines pages 3-5) - Zinc deficiency/low zinc status increases susceptibility to Cd kidney injury; zinc status modifies tubular toxicity risk in human evidence. (nordberg2025metallothioneinandother pages 9-11)

Co-exposures: - Co-exposure to inorganic arsenic can potentiate Cd nephrotoxicity with more-than-additive tubular effects, and MT status may modify susceptibility in animal data summarized in review. (nordberg2025metallothioneinandother pages 12-14, nordberg2025metallothioneinandother pages 11-12)

2.3 Protective factors

  • Adequate zinc status is associated with lower prevalence of Cd-related tubular dysfunction; higher Zn/Cd quotients were strongly protective in population data summarized in a kidney-focused review. (nordberg2025metallothioneinandother pages 11-12)
  • Nutritional sufficiency (iron/zinc/selenium; calcium) is repeatedly proposed as a practical exposure-mitigation approach for oral Cd assimilation. (balalimood2025recentadvancesin pages 9-11, satarug2025hypertensioninpeople pages 16-17)

2.4 Gene–environment interactions (current evidence base)

Cadmium toxicity is not typically modeled as a monogenic disorder; instead, gene–environment interactions are framed through toxicokinetics/toxicodynamics modifiers. Metallothionein (MT) induction and MT-related biomarkers/antibodies are repeatedly discussed as determinants of Cd distribution and kidney injury susceptibility in human and animal evidence. (nordberg2025metallothioneinandother pages 12-14, nordberg2025metallothioneinandother pages 9-11)

Ontology suggestions (non-exhaustive): CHEBI: cadmium(2+) (cadmium ion); environmental exposure to heavy metal; exposure to tobacco smoke.

3. Phenotypes

Cadmium toxicity phenotypes depend on dose and route.

3.1 Acute cadmium poisoning (typically inhalation)

Core manifestations: respiratory irritation progressing over hours to pneumonitis/respiratory distress. - A clinical review describes symptom onset within 6–12 hours after inhalation with cough/fever/respiratory distress and potential progression to hypoxia and pulmonary failure. (balalimood2025recentadvancesin pages 9-11) - Quantitative lethality estimate in one review: “The inhalation exposure to 5 mg/m3 for 8 h may be lethal.” (balalimood2025recentadvancesin pages 11-12)

Suggested HPO terms (examples): - Dyspnea (HP:0002094) - Cough (HP:0012735) - Fever (HP:0001945) - Hypoxemia (HP:0012418)

3.2 Chronic cadmium toxicity (bioaccumulation)

Kidney (most sensitive/critical target): - Renal tubular injury with low-molecular-weight proteinuria; chronic kidney disease risk; effect biomarkers include urinary β2-microglobulin and urinary NAG; clinical endpoints include eGFR decline and albuminuria/proteinuria. (chakif2026heavymetaltoxicity pages 12-13, nordberg2025metallothioneinandother pages 9-11) - Chronic renal injury is often described as difficult to reverse once established; a review emphasizes that tubular biomarkers may reflect more irreversible injury compared with albuminuria changes following reductions in blood Cd. (nordberg2025metallothioneinandother pages 9-11)

Bone: osteomalacia/osteoporosis/fractures (classically Itai-itai disease in severe exposures). (balalimood2025recentadvancesin pages 9-11, chakif2026heavymetaltoxicity pages 12-13)

Neurologic/cognitive: neurotoxicity signals in population studies (see Epidemiology/Statistics). (lu2024associationofurinary pages 1-2)

Cardiovascular: hypertension risk and related kidney-mediated mechanisms are discussed in expert reviews. (satarug2025hypertensioninpeople pages 10-12)

Suggested HPO terms (examples): - Proteinuria (HP:0000093) - Albuminuria (HP:0000097) - Abnormal glomerular filtration rate (HP:0012211) - Renal tubular dysfunction (HP:0000126) - Osteoporosis (HP:0000939) - Bone pain (HP:0002653)

Quality of life impacts (evidence directionality): In severe or chronic exposure, renal dysfunction and bone disease plausibly impair mobility and daily functioning; however, standardized QoL metrics (SF-36/EQ-5D) were not captured in the retrieved tool evidence.

4. Genetic/Molecular Information

4.1 Causal genes / pathogenic variants

Cadmium poisoning is not a Mendelian disorder in the retrieved evidence; thus no causal gene list or pathogenic variant catalog is appropriate as “disease-causing” in the classical clinical genetics sense.

4.2 Molecular modifiers and key targets (mechanistic relevance)

Metallothionein (MT): central protective/sequestration protein in Cd toxicokinetics and renal tubular handling. MT influences transport of Cd to renal tubules and binds Cd intracellularly, modulating injury risk. (nordberg2025metallothioneinandother pages 12-14, nordberg2025metallothioneinandother pages 9-11)

Metal transporters implicated in uptake (review evidence): DMT1, ZIP14, ATP7A, TRPV6 are discussed as routes by which Cd enters cells, with higher absorption in low-iron states. (satarug2026aretheguidelines pages 3-5)

Ontology suggestions: - GO (biological process): response to cadmium ion; metal ion transport; response to oxidative stress; renal tubular cell apoptotic process; inflammatory response. - CL (cell types): kidney proximal tubule epithelial cell (CL:0002306); hepatocyte (CL:0000182); macrophage (CL:0000235).

5. Environmental Information

Environmental factors: cadmium contamination of air, water, soil, and food chain; occupational industrial emissions; battery waste. (balalimood2025recentadvancesin pages 9-11)

Lifestyle factors: cigarette smoking is repeatedly highlighted as a major preventable contributor to Cd body burden; smoking cessation is explicitly recommended as a cadmium reduction strategy. (chakif2026heavymetaltoxicity pages 16-17)

Infectious agents: not applicable.

6. Mechanism / Pathophysiology (Causal Chain)

A consensus mechanistic chain in the retrieved evidence is:

1) Exposure and absorption: via inhalation (occupational/tobacco) and ingestion (diet). (balalimood2025recentadvancesin pages 9-11, chakif2026heavymetaltoxicity pages 7-8)

2) Distribution and long residence time: Cd binds proteins including metallothionein and concentrates in the renal cortex; a recent review states cadmium has a very long biologic half-life (~20–30 years). (chakif2026heavymetaltoxicity pages 12-13)

3) Cellular entry and injury pathways: Cd can hijack metal transporters (e.g., DMT1/ZIP14/ATP7A/TRPV6) to enter target cells. (satarug2026aretheguidelines pages 3-5)

4) Renal tubular injury and functional decline: proximal tubular dysfunction is a central clinical manifestation, with effect biomarkers including β2-microglobulin and NAG. (chakif2026heavymetaltoxicity pages 12-13, chakif2026heavymetaltoxicity pages 14-16)

5) System-level outcomes: CKD progression (eGFR loss), proteinuria/albuminuria; downstream effects include bone demineralization/fractures and cardiometabolic outcomes. (chakif2026heavymetaltoxicity pages 12-13, satarug2025hypertensioninpeople pages 10-12)

Oxidative stress/mitochondrial dysfunction: Reviews describe Cd-driven ROS generation and mitochondrial impairment; expert commentary also links Cd exposure to oxidative stress and inflammation across organs. (satarug2026aretheguidelines pages 16-18, balalimood2025recentadvancesin pages 9-11)

Metallothionein and zinc interactions: MT is portrayed as protective by binding Cd, and zinc status modifies susceptibility (e.g., higher Zn/Cd quotients protective against tubular dysfunction in population evidence summarized by Nordberg & Nordberg). (nordberg2025metallothioneinandother pages 11-12)

Advanced/omics evidence: mixture modeling and pathway-based analyses are emerging in human studies (e.g., mixed metal exposure modeling in NHANES; BKMR/WQS approaches), supporting a shift from single-metal to mixture-aware causal inference. (shi2024associationsofmixed pages 1-2)

7. Anatomical Structures Affected

Primary organs: - Kidney (renal cortex; proximal tubule): principal site of accumulation and chronic injury. (chakif2026heavymetaltoxicity pages 12-13) - Lung: key site for acute inhalational injury. (balalimood2025recentadvancesin pages 9-11) - Bone/skeleton: demineralization/osteomalacia/osteoporosis and fracture risk. (chakif2026heavymetaltoxicity pages 12-13)

Secondary systems: cardiovascular (hypertension), nervous system (neurotoxicity/cognition), liver involvement in toxicokinetics. (satarug2025hypertensioninpeople pages 10-12, lu2024associationofurinary pages 1-2)

Ontology suggestions: - UBERON: kidney cortex; proximal convoluted tubule; lung; bone tissue. - GO Cellular Component: mitochondrion; cytosol; nucleus.

8. Temporal Development

Onset patterns: - Acute: subacute respiratory syndrome hours after inhalation (6–12 h described). (balalimood2025recentadvancesin pages 9-11) - Chronic: insidious, cumulative exposure with long tissue half-life, manifesting over years to decades. (chakif2026heavymetaltoxicity pages 12-13)

Progression: - Expert review emphasizes that Cd-related loss of eGFR due to nephron destruction is irreversible once established (“eGFR deterioration due to Cd-induced nephron destruction is irreversible”). (satarug2025hypertensioninpeople pages 16-17)

9. Inheritance and Population

Cadmium poisoning is not inherited; it is primarily exposure-driven.

Epidemiology/burden (recent quantitative data): - In NHANES 2011–2020 (n=9,056), kidney stone prevalence was 10.82%, and urinary Cd was associated with higher kidney stone odds (see Section 5 Table). (ye2023nationalanalysisof pages 4-5) - In NHANES 2011–2018 mixture analysis (n=3,080), CKD prevalence was 18.90% (582 cases) and high mixed-metal exposure increased CKD odds; cadmium was a high-importance contributor in BKMR (PIP 0.911 in urine; 0.845 in blood). (shi2024associationsofmixed pages 4-5) - In a Korean vulnerable-area cohort (n=298; mean age 70.3), exposure-area mean blood Cd was 1.89 µg/L vs 0.89 µg/L in control; urinary Cd 2.11 µg/L vs 1.11 µg/L, with renal biomarker associations. (kwon2023associationbetweenlevels pages 1-2)

Demographics: Susceptibility patterns include sex differences and higher absorption risk in low-iron states; race/ethnicity differences appear in some outcomes (e.g., cognition association in REGARDS observed among White but not Black participants). (satarug2026aretheguidelines pages 3-5, lu2024associationofurinary pages 1-2)

10. Diagnostics

Core diagnostic strategy: exposure history + biomonitoring + organ injury assessment.

10.1 Exposure biomarkers

  • Urine cadmium (creatinine-corrected): emphasized as a marker of Cd body burden; one review notes urine is often preferred for cadmium body burden. (chakif2026heavymetaltoxicity pages 14-16)
  • Blood cadmium: more reflective of recent/ongoing exposure in many frameworks; correlated with some kidney outcomes and albuminuria trajectories in review evidence. (nordberg2025metallothioneinandother pages 9-11)

10.2 Effect biomarkers (kidney)

Common effect biomarkers in human studies/reviews include: - Urinary β2-microglobulin (β2M): tubular reabsorptive dysfunction marker. A widely used threshold is β2M excretion 300 µg/g creatinine (β2-microglobulinuria). (satarug2025hypertensioninpeople pages 14-16) - Urinary NAG: tubular injury marker. Thresholds vary by study (examples include UNAG >23 U/g creatinine in a review figure legend and NAG >11.5 U/L as a reference exceedance in a regional cohort study). (nordberg2025metallothioneinandother pages 11-12, kwon2023associationbetweenlevels pages 9-10) - Albuminuria/proteinuria and eGFR: clinically relevant endpoints; expert analysis argues eGFR decline should be prioritized in risk assessment relative to β2M-based endpoints. (satarug2026aretheguidelines pages 3-5, satarug2025hypertensioninpeople pages 10-12)

Threshold examples (interpretation is study-specific): - A 2024 review states urinary Cd <10 µg/g creatinine is associated with reversible renal dysfunction, while >10 µg/g creatinine can cause irreversible damage. (vamsi2024cadmiumtoxicityunveiling pages 8-9) - Another review suggests chronic renal risk may occur at ~2–5 µg/g creatinine urinary Cd. (chakif2026heavymetaltoxicity pages 14-16)

10.3 Differential diagnosis

Not systematically enumerated in the retrieved tool evidence; clinically, differential for tubular proteinuria/CKD includes diabetes, hypertension, other nephrotoxins (e.g., lead), and multiple-metal co-exposures, consistent with mixture analyses. (shi2024associationsofmixed pages 1-2)

11. Outcome / Prognosis

Renal prognosis: Chronic Cd exposure is associated with persistent renal tubular injury and progressive CKD risk. Expert commentary emphasizes irreversibility of eGFR deterioration once nephron destruction occurs. (satarug2025hypertensioninpeople pages 16-17)

Population outcome signals: - In a Thai cohort analysis (n=737), risks of low eGFR and albuminuria rose ~twofold per doubling ECd/Ccr, and severe tubular injury risk (NAG/Ccr) increased with Cd burden. (satarug2024urinarynacetylglucosaminidasein pages 12-13)

Mortality rates and formal survival estimates were not retrieved in the tool evidence.

12. Treatment

General principle: remove exposure and provide supportive care; routine chelation is controversial for cadmium.

12.1 Immediate management (acute inhalation/ingestion)

A clinical review emphasizes supportive measures including decontamination and pulmonary management. For acute cases it describes GI decontamination (e.g., gastric lavage when appropriate) and the use of corticosteroids for pulmonary inflammation in some contexts; dialysis is generally not effective except in renal failure. (balalimood2025recentadvancesin pages 11-12)

12.2 Chelation therapy (evidence limitations)

  • Expert review statement: “therapeutically effective chelation treatment to remove Cd from the kidneys does not exist.” (satarug2025hypertensioninpeople pages 16-17)
  • Dimercaprol (BAL) is discouraged/contraindicated for cadmium in review evidence because Cd–BAL complexes can be more nephrotoxic than cadmium alone. (vamsi2024cadmiumtoxicityunveiling pages 8-9)
  • Succimer (DMSA), DMPS, and DTPA are discussed as possible chelation options in some reviews, but with uncertain clinical benefit and important limitations; multiple sources stress that chelation should only be considered if benefits outweigh harms and that “source control is the anchor.” (balalimood2025recentadvancesin pages 11-12, chakif2026heavymetaltoxicity pages 16-17)

12.3 Emerging/experimental strategies

A prevention-oriented approach using an orally administered chelating polymer (Chitosan@DOTAGA) was tested in mice to chelate Cd in the gut and reduce systemic effects from contaminated diet exposure (7 mg/kg cadmium in food). The polymer remained confined to the GI tract and reduced pathology scores (kidney score control 2 vs saline 27 vs treated 7) in this model. (howard2023combatingleadand pages 6-8)

MAXO suggestions (non-exhaustive): - Removal of exposure source; smoking cessation; occupational exposure mitigation; supportive care; toxicology consultation; chelation therapy (restricted/conditional).

13. Prevention

Prevention is emphasized as the dominant strategy: - Smoking cessation and dietary/exposure avoidance are repeatedly recommended. (chakif2026heavymetaltoxicity pages 16-17, satarug2025hypertensioninpeople pages 16-17) - Occupational hygiene and ventilation; limiting industrial Cd uses; proper battery recycling/disposal; and nutrition optimization (iron/zinc/selenium adequacy) to reduce uptake are recommended in clinical management review evidence. (balalimood2025recentadvancesin pages 9-11, balalimood2025recentadvancesin pages 11-12)

14. Other Species / Natural Disease

Naturally occurring cadmium toxicosis in animals was not explicitly retrieved in the tool evidence; however, multiple reviews describe cadmium toxicity across humans and animals and emphasize conserved renal and bone targets. (nordberg2025metallothioneinandother pages 17-18)

15. Model Organisms

Mouse models (in vivo): - A 2023 mouse study used dietary Cd exposure (7 mg/kg in food) and assessed mitigation via oral chelating polymer (Chitosan@DOTAGA). The polymer’s biodistribution was confined to the digestive tract and it reduced kidney and liver pathology scores compared with saline-exposed mice. (howard2023combatingleadand pages 6-8, howard2023combatingleadand pages 5-6)

Model limitations: exposure regimen and doses may not reflect human chronic low-dose dietary exposure; translation requires careful toxicokinetic scaling.

Recent Developments and Real-World Implementations (2023–2024 emphasis)

Recent literature shows a shift toward (i) mixture-aware exposure modeling (e.g., BKMR/WQS in NHANES), (ii) lower-effect thresholds and debates about which renal endpoints best reflect clinically meaningful harm (eGFR vs β2M), and (iii) preventive “gut chelation” or exposure-blocking strategies in preclinical models. (shi2024associationsofmixed pages 4-5, satarug2025hypertensioninpeople pages 10-12, howard2023combatingleadand pages 6-8)

Study (first author, year) Population/design Exposure metric Outcome(s) Key quantitative results Notes
Ye, 2023 NHANES 2011–2020 cross-sectional analysis; 9,056 U.S. adults aged ≥20 years Urinary cadmium, quartiles: Q1 0.025–0.104 µg/L; Q2 0.105–0.218 µg/L; Q3 0.219–0.435 µg/L; Q4 0.435–7.581 µg/L Self-reported kidney stones Kidney stone prevalence 10.82%. Fully adjusted ORs vs Q1: Q2 1.40 (95% CI 1.06–1.84), Q3 1.18 (0.88–1.59), Q4 1.54 (1.10–2.06); continuous urinary Cd OR 1.13 (1.01–1.26). Restricted cubic spline showed a non-linear association (P for non-linear <0.001). DOI: https://doi.org/10.3389/fpubh.2023.1146263 (ye2023nationalanalysisof pages 1-2, ye2023nationalanalysisof pages 4-5) Suggests even relatively low urinary Cd ranges are associated with higher kidney stone odds; cross-sectional design limits causal inference.
Shi, 2024 NHANES 2011–2018 cross-sectional mixture analysis; 3,080 adults, 582 CKD cases (18.90%) Urine and whole-blood metal mixtures including cadmium, manganese, lead, mercury Chronic kidney disease (CKD) High mixed-metal exposure associated with increased CKD odds: urine mixture OR 1.58 (95% CI 1.26–1.99); whole-blood mixture OR 1.67 (1.19–2.34). BKMR PIPs in overall population highlighted urine Cd 0.911 and blood Cd 0.845 among important contributors. DOI: https://doi.org/10.1038/s41598-024-63858-3 (shi2024associationsofmixed pages 4-5, shi2024associationsofmixed pages 1-2) Cadmium acted within a co-exposure context rather than as a single-metal model; interactions were more evident in participants with T2DM.
Kwon, 2023 Korean environmentally vulnerable-area study; n=298 total (low-exposure abandoned mine n=74, high-exposure abandoned mine n=68, refinery n=121, control n=35); mean age 70.3 years Blood Cd and urinary Cd; heavy metal biomonitoring in exposed vs control regions Renal biomarkers: urinary NAG, urinary β2-microglobulin (β2-MG), eGFR In exposure areas vs control: mean blood Cd 1.89 vs 0.89 µg/L; urinary Cd 2.11 vs 1.11 µg/L. Blood Cd in refinery area had OR 38 for exceeding reference value vs control; urinary Cd was 7-fold higher in the low-exposure mine area vs control. Urinary Cd positively correlated with NAG in all areas; blood Cd associated with increased odds of β2-MG >300 µg/L and eGFR <60 mL/min/1.73 m²; NAG reference threshold >11.5 U/L. DOI: https://doi.org/10.1038/s41598-022-27292-7 (kwon2023associationbetweenlevels pages 9-10, kwon2023associationbetweenlevels pages 1-2) Supports renal tubular injury as a prominent human signal of environmental Cd exposure; small regional study but with strong area contrasts.
Satarug, 2024 Thai environmentally exposed cohort/cross-sectional analysis; 737 non-diabetic adults, 9.1% with eGFR ≤60 mL/min/1.73 m² Urinary Cd normalized to creatinine clearance (ECd/Ccr); renal biomarkers normalized similarly Low eGFR, albuminuria, tubular injury (NAG), β2-microglobulin-related tubular dysfunction Risks of low eGFR and albuminuria rose twofold per doubling ECd/Ccr. Doubling ECd/Ccr increased risk of severe tubular injury measured by NAG/Ccr (POR 4.80, p=0.015). ENAG/Ccr associated with ECd/Ccr in men β=0.447 and women β=0.394; inversely associated with eGFR in women β=-0.178 and in high-Cd body burden group β=-0.223. Reported benchmark/threshold values include ECd/Ecr 0.5 µg/g linked to 2.6- to 3.6-fold higher odds of abnormal NAG excretion; BMDLs 0.5–0.8 and 0.7–1.2 µg/g creatinine; some studies suggest <0.3 µg/g. DOI: https://doi.org/10.3390/toxics12110775 (satarug2024urinarynacetylglucosaminidasein pages 12-13) Highlights that tubular biomarkers and GFR decline may reflect partly different mechanisms/kinetics of Cd nephrotoxicity.
Lu, 2024 REGARDS prospective cohort subcohort; 2,172 adults free of baseline cognitive impairment/stroke; mean age 64.1 years; 54.8% female; 38.7% Black; average follow-up ~10 years Baseline urinary creatinine-corrected cadmium; dichotomized at median or analyzed by tertiles Global cognitive impairment and domain-based cognitive impairment During follow-up: 195 cases of global cognitive impairment and 53 domain-based cases. No overall association in full sample, but among White participants, high urinary Cd (≥median) was associated with doubled odds of global cognitive impairment: OR 2.07 (95% CI 1.18–3.64). Median urinary Cd was similar by race: Black 0.414 µg/g, White 0.407 µg/g. DOI: https://doi.org/10.1212/WNL.0000000000209808 (lu2024associationofurinary pages 1-2, lu2024associationofurinary pages 4-5, lu2024associationofurinary pages 8-9, lu2024associationofurinary pages 2-4) Prospective design strengthens temporal inference; association appeared race-specific in this cohort and was not seen for domain-specific impairment overall.

Table: This table summarizes recent human studies linking cadmium exposure to kidney, renal biomarker, and cognitive outcomes, emphasizing 2023–2024 evidence. It is useful for quickly comparing exposure metrics, sample sizes, and quantitative effect estimates relevant to cadmium poisoning and chronic cadmium toxicity.

Visual Evidence (Tables)

The following extracted tables provide visual documentation of participant characteristics and measured blood/urine cadmium levels by region in a vulnerable-area cohort study.

  • Participant characteristics and biomarker tables (cadmium levels; renal indicators) from Kwon et al. (Scientific Reports, 2023). (kwon2023associationbetweenlevels media 0a68bf68, kwon2023associationbetweenlevels media a1f51e53)

Notes on Evidence Quality and Gaps

  • Many quantitative human findings come from cross-sectional analyses (NHANES), which support association but not definitive causality. (ye2023nationalanalysisof pages 1-2, shi2024associationsofmixed pages 1-2)
  • Prospective evidence exists for some outcomes (e.g., cognition in REGARDS), but findings can be subgroup-dependent and require replication. (lu2024associationofurinary pages 1-2)
  • Standard ontology identifiers (MONDO/MeSH/ICD) were not retrievable from tool evidence in this run and should be added from dedicated ontology resources in a subsequent curation step. (artifact-00)

References

  1. (balalimood2025recentadvancesin pages 9-11): Mahdi Balali-Mood, Nastaran Eizadi-Mood, Hossein Hassanian-Moghaddam, Leila Etemad, Mohammad Moshiri, Maryam Vahabzadeh, and Mahmood Sadeghi. Recent advances in the clinical management of intoxication by five heavy metals: mercury, lead, chromium, cadmium and arsenic. Heliyon, 11:e42696, Feb 2025. URL: https://doi.org/10.1016/j.heliyon.2025.e42696, doi:10.1016/j.heliyon.2025.e42696. This article has 65 citations.

  2. (chakif2026heavymetaltoxicity pages 12-13): Dib Chakif and Julien Furrer. Heavy metal toxicity in clinical and environmental health: sources, mechanisms, diagnostics, and evidence-based management of mercury, lead, cadmium, and arsenic. International Journal of Molecular Sciences, 27:3513, Apr 2026. URL: https://doi.org/10.3390/ijms27083513, doi:10.3390/ijms27083513. This article has 0 citations.

  3. (vamsi2024cadmiumtoxicityunveiling pages 8-9): N. Mohana Vamsi, J. Pavan Kumar, K. Ramadevi, and P. Swathi. Cadmium toxicity: unveiling the threat to human health. Indian Journal of Pharmaceutical Sciences, Jan 2024. URL: https://doi.org/10.36468/pharmaceutical-sciences.1427, doi:10.36468/pharmaceutical-sciences.1427. This article has 27 citations.

  4. (shi2024associationsofmixed pages 1-2): Xiaoru Shi, Xiao Wang, Jia Zhang, Ying Dang, Changping Ouyang, Jinhua Pan, Aimin Yang, and Xiaobin Hu. Associations of mixed metal exposure with chronic kidney disease from nhanes 2011–2018. Scientific Reports, Jun 2024. URL: https://doi.org/10.1038/s41598-024-63858-3, doi:10.1038/s41598-024-63858-3. This article has 29 citations and is from a peer-reviewed journal.

  5. (balalimood2025recentadvancesin pages 11-12): Mahdi Balali-Mood, Nastaran Eizadi-Mood, Hossein Hassanian-Moghaddam, Leila Etemad, Mohammad Moshiri, Maryam Vahabzadeh, and Mahmood Sadeghi. Recent advances in the clinical management of intoxication by five heavy metals: mercury, lead, chromium, cadmium and arsenic. Heliyon, 11:e42696, Feb 2025. URL: https://doi.org/10.1016/j.heliyon.2025.e42696, doi:10.1016/j.heliyon.2025.e42696. This article has 65 citations.

  6. (chakif2026heavymetaltoxicity pages 7-8): Dib Chakif and Julien Furrer. Heavy metal toxicity in clinical and environmental health: sources, mechanisms, diagnostics, and evidence-based management of mercury, lead, cadmium, and arsenic. International Journal of Molecular Sciences, 27:3513, Apr 2026. URL: https://doi.org/10.3390/ijms27083513, doi:10.3390/ijms27083513. This article has 0 citations.

  7. (nordberg2025metallothioneinandother pages 9-11): Gunnar F. Nordberg and Monica Nordberg. Metallothionein and other factors influencing cadmium-induced kidney dysfunction: review and commentary. Biomolecules, 15:1083, Jul 2025. URL: https://doi.org/10.3390/biom15081083, doi:10.3390/biom15081083. This article has 8 citations.

  8. (nordberg2025metallothioneinandother pages 12-14): Gunnar F. Nordberg and Monica Nordberg. Metallothionein and other factors influencing cadmium-induced kidney dysfunction: review and commentary. Biomolecules, 15:1083, Jul 2025. URL: https://doi.org/10.3390/biom15081083, doi:10.3390/biom15081083. This article has 8 citations.

  9. (chakif2026heavymetaltoxicity pages 14-16): Dib Chakif and Julien Furrer. Heavy metal toxicity in clinical and environmental health: sources, mechanisms, diagnostics, and evidence-based management of mercury, lead, cadmium, and arsenic. International Journal of Molecular Sciences, 27:3513, Apr 2026. URL: https://doi.org/10.3390/ijms27083513, doi:10.3390/ijms27083513. This article has 0 citations.

  10. (nordberg2025metallothioneinandother pages 11-12): Gunnar F. Nordberg and Monica Nordberg. Metallothionein and other factors influencing cadmium-induced kidney dysfunction: review and commentary. Biomolecules, 15:1083, Jul 2025. URL: https://doi.org/10.3390/biom15081083, doi:10.3390/biom15081083. This article has 8 citations.

  11. (kwon2023associationbetweenlevels pages 9-10): Jung-Yeon Kwon, Seungho Lee, Ulziikhishig Surenbaatar, Hyoun-Ju Lim, Byoung-Gwon Kim, Sang-Yong Eom, Yong Min Cho, Woo Jin Kim, Byeng-Chul Yu, Kwan Lee, and Young-Seoub Hong. Association between levels of exposure to heavy metals and renal function indicators of residents in environmentally vulnerable areas. Scientific Reports, Feb 2023. URL: https://doi.org/10.1038/s41598-022-27292-7, doi:10.1038/s41598-022-27292-7. This article has 40 citations and is from a peer-reviewed journal.

  12. (chakif2026heavymetaltoxicity pages 16-17): Dib Chakif and Julien Furrer. Heavy metal toxicity in clinical and environmental health: sources, mechanisms, diagnostics, and evidence-based management of mercury, lead, cadmium, and arsenic. International Journal of Molecular Sciences, 27:3513, Apr 2026. URL: https://doi.org/10.3390/ijms27083513, doi:10.3390/ijms27083513. This article has 0 citations.

  13. (chakif2026heavymetaltoxicity pages 8-9): Dib Chakif and Julien Furrer. Heavy metal toxicity in clinical and environmental health: sources, mechanisms, diagnostics, and evidence-based management of mercury, lead, cadmium, and arsenic. International Journal of Molecular Sciences, 27:3513, Apr 2026. URL: https://doi.org/10.3390/ijms27083513, doi:10.3390/ijms27083513. This article has 0 citations.

  14. (satarug2025hypertensioninpeople pages 16-17): Soisungwan Satarug. Hypertension in people exposed to environmental cadmium: roles for 20-hydroxyeicosatetraenoic acid in the kidney. Journal of Xenobiotics, Aug 2025. URL: https://doi.org/10.3390/jox15040122, doi:10.3390/jox15040122. This article has 2 citations.

  15. (satarug2026aretheguidelines pages 3-5): Soisungwan Satarug. Are the guidelines for dietary and workplace exposure to cadmium adequate? Unknown journal, Apr 2026. URL: https://doi.org/10.20944/preprints202604.0484.v1, doi:10.20944/preprints202604.0484.v1.

  16. (lu2024associationofurinary pages 1-2): Liping Lu, Yijia Zhang, Meghan Angley, Shai Bejerano, John D. Brockman, Leslie A. McClure, Frederick W. Unverzagt, Alyce D. Fly, and Ka Kahe. Association of urinary cadmium concentration with cognitive impairment in us adults. Neurology, Oct 2024. URL: https://doi.org/10.1212/wnl.0000000000209808, doi:10.1212/wnl.0000000000209808. This article has 10 citations and is from a highest quality peer-reviewed journal.

  17. (satarug2025hypertensioninpeople pages 10-12): Soisungwan Satarug. Hypertension in people exposed to environmental cadmium: roles for 20-hydroxyeicosatetraenoic acid in the kidney. Journal of Xenobiotics, Aug 2025. URL: https://doi.org/10.3390/jox15040122, doi:10.3390/jox15040122. This article has 2 citations.

  18. (satarug2026aretheguidelines pages 16-18): Soisungwan Satarug. Are the guidelines for dietary and workplace exposure to cadmium adequate? Unknown journal, Apr 2026. URL: https://doi.org/10.20944/preprints202604.0484.v1, doi:10.20944/preprints202604.0484.v1.

  19. (ye2023nationalanalysisof pages 4-5): Zhenyang Ye, Zaizhi Chen, Jin-Ying Luo, Lijing Xu, Dongping Fan, and Jia Wang. National analysis of urinary cadmium concentration and kidney stone: evidence from nhanes (2011–2020). Frontiers in Public Health, Mar 2023. URL: https://doi.org/10.3389/fpubh.2023.1146263, doi:10.3389/fpubh.2023.1146263. This article has 8 citations.

  20. (shi2024associationsofmixed pages 4-5): Xiaoru Shi, Xiao Wang, Jia Zhang, Ying Dang, Changping Ouyang, Jinhua Pan, Aimin Yang, and Xiaobin Hu. Associations of mixed metal exposure with chronic kidney disease from nhanes 2011–2018. Scientific Reports, Jun 2024. URL: https://doi.org/10.1038/s41598-024-63858-3, doi:10.1038/s41598-024-63858-3. This article has 29 citations and is from a peer-reviewed journal.

  21. (kwon2023associationbetweenlevels pages 1-2): Jung-Yeon Kwon, Seungho Lee, Ulziikhishig Surenbaatar, Hyoun-Ju Lim, Byoung-Gwon Kim, Sang-Yong Eom, Yong Min Cho, Woo Jin Kim, Byeng-Chul Yu, Kwan Lee, and Young-Seoub Hong. Association between levels of exposure to heavy metals and renal function indicators of residents in environmentally vulnerable areas. Scientific Reports, Feb 2023. URL: https://doi.org/10.1038/s41598-022-27292-7, doi:10.1038/s41598-022-27292-7. This article has 40 citations and is from a peer-reviewed journal.

  22. (satarug2025hypertensioninpeople pages 14-16): Soisungwan Satarug. Hypertension in people exposed to environmental cadmium: roles for 20-hydroxyeicosatetraenoic acid in the kidney. Journal of Xenobiotics, Aug 2025. URL: https://doi.org/10.3390/jox15040122, doi:10.3390/jox15040122. This article has 2 citations.

  23. (satarug2024urinarynacetylglucosaminidasein pages 12-13): Soisungwan Satarug. Urinary n-acetylglucosaminidase in people environmentally exposed to cadmium is minimally related to cadmium-induced nephron destruction. Toxics, 12:775, Oct 2024. URL: https://doi.org/10.3390/toxics12110775, doi:10.3390/toxics12110775. This article has 7 citations.

  24. (howard2023combatingleadand pages 6-8): Jordyn Ann Howard, Halyna Kuznietsova, Natalia Dziubenko, Axel Aigle, Marco Natuzzi, Eloise Thomas, Vladimir Lysenko, Laurent David, Thomas Brichart, François Lux, and Olivier Tillement. Combating lead and cadmium exposure with an orally administered chitosan-based chelating polymer. Scientific Reports, Feb 2023. URL: https://doi.org/10.1038/s41598-023-28968-4, doi:10.1038/s41598-023-28968-4. This article has 23 citations and is from a peer-reviewed journal.

  25. (nordberg2025metallothioneinandother pages 17-18): Gunnar F. Nordberg and Monica Nordberg. Metallothionein and other factors influencing cadmium-induced kidney dysfunction: review and commentary. Biomolecules, 15:1083, Jul 2025. URL: https://doi.org/10.3390/biom15081083, doi:10.3390/biom15081083. This article has 8 citations.

  26. (howard2023combatingleadand pages 5-6): Jordyn Ann Howard, Halyna Kuznietsova, Natalia Dziubenko, Axel Aigle, Marco Natuzzi, Eloise Thomas, Vladimir Lysenko, Laurent David, Thomas Brichart, François Lux, and Olivier Tillement. Combating lead and cadmium exposure with an orally administered chitosan-based chelating polymer. Scientific Reports, Feb 2023. URL: https://doi.org/10.1038/s41598-023-28968-4, doi:10.1038/s41598-023-28968-4. This article has 23 citations and is from a peer-reviewed journal.

  27. (ye2023nationalanalysisof pages 1-2): Zhenyang Ye, Zaizhi Chen, Jin-Ying Luo, Lijing Xu, Dongping Fan, and Jia Wang. National analysis of urinary cadmium concentration and kidney stone: evidence from nhanes (2011–2020). Frontiers in Public Health, Mar 2023. URL: https://doi.org/10.3389/fpubh.2023.1146263, doi:10.3389/fpubh.2023.1146263. This article has 8 citations.

  28. (lu2024associationofurinary pages 4-5): Liping Lu, Yijia Zhang, Meghan Angley, Shai Bejerano, John D. Brockman, Leslie A. McClure, Frederick W. Unverzagt, Alyce D. Fly, and Ka Kahe. Association of urinary cadmium concentration with cognitive impairment in us adults. Neurology, Oct 2024. URL: https://doi.org/10.1212/wnl.0000000000209808, doi:10.1212/wnl.0000000000209808. This article has 10 citations and is from a highest quality peer-reviewed journal.

  29. (lu2024associationofurinary pages 8-9): Liping Lu, Yijia Zhang, Meghan Angley, Shai Bejerano, John D. Brockman, Leslie A. McClure, Frederick W. Unverzagt, Alyce D. Fly, and Ka Kahe. Association of urinary cadmium concentration with cognitive impairment in us adults. Neurology, Oct 2024. URL: https://doi.org/10.1212/wnl.0000000000209808, doi:10.1212/wnl.0000000000209808. This article has 10 citations and is from a highest quality peer-reviewed journal.

  30. (lu2024associationofurinary pages 2-4): Liping Lu, Yijia Zhang, Meghan Angley, Shai Bejerano, John D. Brockman, Leslie A. McClure, Frederick W. Unverzagt, Alyce D. Fly, and Ka Kahe. Association of urinary cadmium concentration with cognitive impairment in us adults. Neurology, Oct 2024. URL: https://doi.org/10.1212/wnl.0000000000209808, doi:10.1212/wnl.0000000000209808. This article has 10 citations and is from a highest quality peer-reviewed journal.

  31. (kwon2023associationbetweenlevels media 0a68bf68): Jung-Yeon Kwon, Seungho Lee, Ulziikhishig Surenbaatar, Hyoun-Ju Lim, Byoung-Gwon Kim, Sang-Yong Eom, Yong Min Cho, Woo Jin Kim, Byeng-Chul Yu, Kwan Lee, and Young-Seoub Hong. Association between levels of exposure to heavy metals and renal function indicators of residents in environmentally vulnerable areas. Scientific Reports, Feb 2023. URL: https://doi.org/10.1038/s41598-022-27292-7, doi:10.1038/s41598-022-27292-7. This article has 40 citations and is from a peer-reviewed journal.

  32. (kwon2023associationbetweenlevels media a1f51e53): Jung-Yeon Kwon, Seungho Lee, Ulziikhishig Surenbaatar, Hyoun-Ju Lim, Byoung-Gwon Kim, Sang-Yong Eom, Yong Min Cho, Woo Jin Kim, Byeng-Chul Yu, Kwan Lee, and Young-Seoub Hong. Association between levels of exposure to heavy metals and renal function indicators of residents in environmentally vulnerable areas. Scientific Reports, Feb 2023. URL: https://doi.org/10.1038/s41598-022-27292-7, doi:10.1038/s41598-022-27292-7. This article has 40 citations and is from a peer-reviewed journal.