Hospital-Acquired Acute Kidney Injury

Complex MONDO:0002492 Pathograph 8 Show in embeddings browser Renal Disease

Hospital-acquired acute kidney injury (HA-AKI) is a common and serious clinical syndrome defined as AKI developing after hospital admission, typically diagnosed using KDIGO serum creatinine and urine output criteria. It represents a convergent endpoint arising from overlapping inpatient insults including sepsis, nephrotoxic drug exposure, perioperative hemodynamic instability, and contrast media administration. HA-AKI affects 10-25% of hospitalized patients overall and up to 50-60% of ICU patients, with in-hospital mortality rates of 30-45% for ICU-acquired cases. Despite advances in recognition and supportive care, effective preventive and therapeutic strategies remain limited, and HA-AKI is an independent risk factor for progression to chronic kidney disease.

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4
Pathophys.
7
Phenotypes
8
Pathograph
5
Genes
4
Medical Actions
4
Subtypes
2
Datasets
1
Trials
1
Deep Research
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Subtypes

4
Sepsis-Associated AKI
AKI developing as a complication of sepsis in hospitalized patients, driven by systemic inflammation, microvascular dysfunction, and tubular cell injury.
Nephrotoxic AKI
AKI caused by exposure to nephrotoxic agents including aminoglycosides, contrast media, NSAIDs, and vancomycin during hospitalization.
Postoperative AKI
AKI developing after major surgery, particularly cardiac, vascular, or abdominal procedures, due to perioperative hemodynamic instability and ischemia.
Contrast-Induced AKI
AKI following intra-arterial or intravenous administration of iodinated contrast media for diagnostic or interventional procedures.
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Pathophysiology

4
Ischemic Tubular Injury
Renal hypoperfusion from sepsis, major surgery, or hemodynamic instability causes ischemia-reperfusion injury to tubular epithelial cells, leading to acute tubular necrosis (ATN), the most common cause of hospital-acquired AKI. Tubular cell death occurs through regulated necrosis pathways including necroptosis and ferroptosis, with subsequent release of cytosolic components that amplify inflammation.
Proximal Tubular Epithelial Cell CL:0002306 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Proximal Tubular Epithelial Cell, annotated with epithelial cell of proximal tubule (CL:0002306). CL:0002306 is a cell type from the Cell Ontology. Peritubular Capillary Endothelial Cell CL:1001033 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Peritubular Capillary Endothelial Cell (CL:1001033). CL:1001033 is a cell type from the Cell Ontology.
Ischemic Response GO:0002931 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Ischemic Response, annotated with response to ischemia (GO:0002931). GO:0002931 is a biological process from the Gene Ontology. Programmed Necrotic Cell Death GO:0097300 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Programmed Necrotic Cell Death (GO:0097300). GO:0097300 is a biological process from the Gene Ontology. Apoptotic Process GO:0006915 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Apoptotic Process (GO:0006915). GO:0006915 is a biological process from the Gene Ontology.
Proximal Tubule UBERON:0004134 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in Proximal Tubule (UBERON:0004134). UBERON:0004134 is an anatomical location from the Uberon multi-species anatomy ontology. Renal Tubule UBERON:0009773 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in Renal Tubule (UBERON:0009773). UBERON:0009773 is an anatomical location from the Uberon multi-species anatomy ontology.
Show evidence (2 references)
PMID:31005270 SUPPORT Model Organism
"Tubular cell death by necrosis and apoptosis is a central feature of renal IRI. Recent research has challenged traditional views of cell death by identifying new pathways in which cells die in a regulated manner but with the morphologic features of necrosis."
Demonstrates that regulated necrosis (necroptosis and ferroptosis) alongside apoptosis are central mechanisms of tubular injury in renal ischemia-reperfusion.
PMID:25057935 SUPPORT Human Clinical
"Acute kidney injury (AKI) represents 18-47% of all causes of hospital-acquired AKI and it is associated with a high incidence of morbidity and mortality especially in patients requiring dialysis."
Postoperative AKI is a major contributor to hospital-acquired AKI, confirming ischemic tubular injury as a predominant mechanism.
Nephrotoxic Injury
Exposure to nephrotoxic agents such as aminoglycosides, contrast media, NSAIDs, and vancomycin causes direct tubular cell damage and apoptosis, contributing to a significant proportion of hospital-acquired AKI cases. Contrast-induced AKI is the third leading cause of hospital-acquired AKI. The drug-induced arm conforms to the conserved drug_induced_nephrotoxicity module: nephrotoxin uptake by proximal tubular cells drives oxidative and mitochondrial injury, converging here on tubular epithelial cell death.
Proximal Tubular Epithelial Cell CL:0002306 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Proximal Tubular Epithelial Cell, annotated with epithelial cell of proximal tubule (CL:0002306). CL:0002306 is a cell type from the Cell Ontology.
Apoptotic Process GO:0006915 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Apoptotic Process (GO:0006915). GO:0006915 is a biological process from the Gene Ontology. Response to Oxidative Stress GO:0006979 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Response to Oxidative Stress (GO:0006979). GO:0006979 is a biological process from the Gene Ontology.
Proximal Tubule UBERON:0004134 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in Proximal Tubule (UBERON:0004134). UBERON:0004134 is an anatomical location from the Uberon multi-species anatomy ontology.
Show evidence (2 references)
PMID:29802583 SUPPORT Human Clinical
"Contrast-induced acute kidney injury (CI-AKI) is the third leading cause of hospital-acquired acute kidney injury."
Confirms that contrast media nephrotoxicity is a major contributor to hospital-acquired AKI.
PMID:34537763 SUPPORT Human Clinical
"In the HA-AKI group, the proportion of patients with prior use of drugs with possible nephrotoxicity was higher than that of patients with prior use of drugs with identified nephrotoxicity (p < 0.05)."
Demonstrates that nephrotoxic drug exposure is a key risk factor for hospital-acquired AKI in older patients.
Sepsis-Associated AKI
Systemic inflammation during sepsis triggers a complex interplay of microvascular dysfunction, inflammatory mediator release, and tubular cell injury through both ischemic and non-ischemic pathways. Recent evidence shows renal blood flow may be normal or increased in early sepsis-AKI, suggesting microvascular and inflammatory mechanisms predominate over global hypoperfusion.
Glomerular Endothelial Cell CL:0002188 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Glomerular Endothelial Cell (CL:0002188). CL:0002188 is a cell type from the Cell Ontology. Kidney Resident Macrophage CL:1000698 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Kidney Resident Macrophage (CL:1000698). CL:1000698 is a cell type from the Cell Ontology. Proximal Tubular Epithelial Cell CL:0002306 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Proximal Tubular Epithelial Cell, annotated with epithelial cell of proximal tubule (CL:0002306). CL:0002306 is a cell type from the Cell Ontology.
Inflammatory Response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Inflammatory Response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. Cell Death GO:0008219 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Cell Death (GO:0008219). GO:0008219 is a biological process from the Gene Ontology.
Renal Glomerulus UBERON:0000074 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in Renal Glomerulus (UBERON:0000074). UBERON:0000074 is an anatomical location from the Uberon multi-species anatomy ontology. Kidney Vasculature UBERON:0006544 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in Kidney Vasculature (UBERON:0006544). UBERON:0006544 is an anatomical location from the Uberon multi-species anatomy ontology.
Show evidence (3 references)
PMID:29273917 SUPPORT Human Clinical
"increasing importance is now attributed to kidney damage resulting from a complex interaction between immunologic mechanisms, inflammatory cascade activation, and deranged coagulation pathways, leading to microvascular dysfunction, endothelial damage, leukocyte/platelet activation with the..."
Describes the multifactorial pathogenesis of sepsis-associated AKI involving inflammation, coagulation, microvascular dysfunction, and tubular injury.
PMID:33494815 SUPPORT Human Clinical
"Up to 60% of patients with sepsis develop acute kidney injury (AKI), which is associated with a poor clinical outcome."
Documents the high incidence of AKI in sepsis patients and its association with poor outcomes, supporting sepsis as a major driver of hospital-acquired AKI.
PMID:25845505 SUPPORT Model Organism
"Sepsis-induced AKI is diagnosed in up to 47% of human ICU patients and is seen as a major public health concern associated with increased mortality and increased progression to chronic kidney disease (CKD)."
Review published in a veterinary journal synthesizing human data on sepsis-induced AKI prevalence in ICU patients.
Mitochondrial Dysfunction
Mitochondrial damage and reduced mitochondrial mass in renal tubular epithelial cells contribute to the pathogenesis of AKI, particularly in sepsis-associated cases. Oxidative DNA damage and impaired mitochondrial quality control pathways exacerbate tubular injury.
Proximal Tubular Epithelial Cell CL:0002306 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Proximal Tubular Epithelial Cell, annotated with epithelial cell of proximal tubule (CL:0002306). CL:0002306 is a cell type from the Cell Ontology.
Response to Oxidative Stress GO:0006979 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Response to Oxidative Stress (GO:0006979). GO:0006979 is a biological process from the Gene Ontology.
Show evidence (2 references)
PMID:33494815 SUPPORT Human Clinical
"Compared to control subjects, sepsis-AKI patients had upregulated mRNA expression of oxidative damage markers, excess mitochondrial DNA damage and lower mitochondrial mass."
Demonstrates that mitochondrial DNA damage and reduced mitochondrial mass are present in the kidneys of sepsis-AKI patients.
PMID:26924060 SUPPORT Model Organism
"Damaged mitochondria accumulate in autophagy-deficient kidneys of mice subjected to ischemia-reperfusion injury, but the precise mechanisms of regulation of mitophagy in AKI are not yet elucidated."
Demonstrates that impaired mitophagy leads to accumulation of damaged mitochondria in AKI, supporting mitochondrial dysfunction as a key pathogenic mechanism.
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Pathograph

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

7
Genitourinary 2
Oliguria HP:0100520 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Oliguria (HP:0100520). HP:0100520 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:35685550 SUPPORT Human Clinical
"HA-AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria."
KDIGO criteria for AKI staging include oliguria as a key diagnostic feature alongside serum creatinine elevation.
Proteinuria HP:0000093 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Proteinuria (HP:0000093). HP:0000093 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:28927644 SUPPORT Human Clinical
"AKI is a risk factor for incident or worsening proteinuria, suggesting a possible mechanism linking AKI and future CKD."
Large Veterans cohort study demonstrates that AKI causes new-onset or worsening proteinuria, with odds ratios of 1.20-1.39 across months of follow-up, and higher odds with more severe AKI stages.
Metabolism 5
Elevated Serum Creatinine Elevated circulating creatinine concentration HP:0003259 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Elevated Serum Creatinine, annotated with Elevated circulating creatinine concentration (HP:0003259). HP:0003259 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:26231194 SUPPORT Human Clinical
"AKI was defined and staged according to Kidney Disease Improving Global Outcomes criteria."
AKI diagnosis relies on serum creatinine elevation according to standardized KDIGO criteria.
Metabolic Acidosis HP:0001942 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Metabolic Acidosis (HP:0001942). HP:0001942 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32397637 SUPPORT Human Clinical
"Established and widely accepted indications for starting RRT include refractory fluid overload, severe hyperkalemia and metabolic acidosis refractory to medical therapy"
Metabolic acidosis is a recognized complication of severe AKI requiring renal replacement therapy.
Hyperkalemia HP:0002153 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hyperkalemia (HP:0002153). HP:0002153 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32397637 SUPPORT Human Clinical
"Established and widely accepted indications for starting RRT include refractory fluid overload, severe hyperkalemia and metabolic acidosis refractory to medical therapy"
Hyperkalemia is a life-threatening complication of AKI and one of the established indications for initiating RRT.
Fluid Overload Edema HP:0000969 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Edema (HP:0000969). HP:0000969 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32397637 SUPPORT Human Clinical
"Established and widely accepted indications for starting RRT include refractory fluid overload, severe hyperkalemia and metabolic acidosis refractory to medical therapy"
Refractory fluid overload is a recognized complication of AKI and an indication for initiating renal replacement therapy.
Azotemia HP:0002157 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Azotemia (HP:0002157). HP:0002157 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32397637 SUPPORT Human Clinical
"Acute complications related to AKI are diverse and depend on the severity of the insult."
Azotemia (accumulation of nitrogenous wastes) is a core feature of AKI driving uremic complications.
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Genetic Associations

5
FTO (Associated)
Gene: FTO hgnc:24678 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is FTO (hgnc:24678). hgnc:24678 is a gene from the HUGO Gene Nomenclature Committee.
Show evidence (1 reference)
PMID:38797326 SUPPORT Computational
"Two novel loci reached genome-wide significance in the meta-analysis: rs11642015 near the FTO locus on chromosome 16 (obesity traits) (odds ratio 1.07 (95% confidence interval, 1.05-1.09))"
GWAS of 54,488 AKI patients identified FTO locus as significantly associated with AKI susceptibility, though the effect was attenuated after adjustment for BMI and diabetes.
SHROOM3 (Associated)
Gene: SHROOM3 hgnc:30422 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is SHROOM3 (hgnc:30422). hgnc:30422 is a gene from the HUGO Gene Nomenclature Committee.
Show evidence (1 reference)
PMID:38797326 SUPPORT Computational
"rs4859682 near the SHROOM3 locus on chromosome 4 (glomerular filtration barrier integrity) (odds ratio 0.95 (95% confidence interval, 0.93-0.96))."
SHROOM3 locus reached genome-wide significance as a protective factor against AKI, with colocalization to previous kidney function studies.
APOE (Associated)
Gene: APOE hgnc:613 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is APOE (hgnc:613). hgnc:613 is a gene from the HUGO Gene Nomenclature Committee.
Show evidence (1 reference)
PMID:19443624 SUPPORT Human Clinical
"Only one polymorphism, APO E e2/e3/e4, had greater than one study showing a significant impact (P < 0.05) on AKI incidence."
Systematic review of 16 AKI genetic studies found APOE as the only replicated genetic association across multiple studies.
NR5A2 (Associated)
Gene: NR5A2 hgnc:7984 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is NR5A2 (hgnc:7984). hgnc:7984 is a gene from the HUGO Gene Nomenclature Committee.
Show evidence (1 reference)
PMID:39636799 SUPPORT Computational
"rs184516290 (chr1:199814965:G:A), near the NR5A2 gene, chr1:199805801:T:TA, also near the NR5A2 gene, and rs117313146 (chr15:31999784:G:C), near the CHRNA7 gene, were associated with S-AKI at the suggestive level in all three models presented."
NR5A2 variants showed consistent suggestive association with sepsis-AKI but did not reach genome-wide significance threshold.
CHRNA7 (Associated)
Gene: CHRNA7 hgnc:1960 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is CHRNA7 (hgnc:1960). hgnc:1960 is a gene from the HUGO Gene Nomenclature Committee.
Show evidence (1 reference)
PMID:39636799 SUPPORT Computational
"rs184516290 (chr1:199814965:G:A), near the NR5A2 gene, chr1:199805801:T:TA, also near the NR5A2 gene, and rs117313146 (chr15:31999784:G:C), near the CHRNA7 gene, were associated with S-AKI at the suggestive level in all three models presented."
CHRNA7 variant showed consistent suggestive association with sepsis-AKI across three models but did not reach genome-wide significance.
💊

Medical Actions

4
Fluid Resuscitation
Action: fluid replacement therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is fluid replacement therapy, annotated with Hydration Therapy (NCIT:C66896). NCIT:C66896 is a clinical intervention from the NCI Thesaurus. Ontology label: Hydration Therapy NCIT:C66896
Intravenous fluid administration to restore renal perfusion in prerenal or ischemic AKI. Isotonic saline or balanced crystalloid solutions are the mainstay of volume expansion.
Show evidence (1 reference)
PMID:29802583 SUPPORT Human Clinical
"The intravenous administration of moderate amounts of isotonic saline solution or bicarbonate solution still represents the principal intervention with documented and acceptable effectiveness for CI-AKI prevention."
Volume expansion with isotonic fluids is the most established preventive and therapeutic measure for AKI.
Nephrotoxin Avoidance
Action: nephrotoxin avoidanceNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is nephrotoxin avoidance, annotated with Lifestyle Therapy (NCIT:C15900). NCIT:C15900 is a clinical intervention from the NCI Thesaurus. Ontology label: Lifestyle Therapy NCIT:C15900
Identification and discontinuation of nephrotoxic medications to prevent further tubular injury. Includes medication review using electronic alert systems and AKI care bundles.
Show evidence (2 references)
PMID:29188454 SUPPORT Human Clinical
"This review found that e-alerts have varying effects on mortality and AKI progression, but decrease the incidence of contrast-induced AKI. The use of AKI bundles delivers statistically significant improvements in mortality and AKI progression."
Electronic alerts and AKI bundles that include nephrotoxin avoidance improve outcomes in hospital-acquired AKI.
PMID:34537763 SUPPORT Human Clinical
"With the increase in the number of patients with continued use of drugs with possible nephrotoxicity after HA-AKI, the clinical outcomes showed a tendency to worsen (p < 0.001)."
Continued nephrotoxic drug exposure after AKI onset worsens outcomes, supporting nephrotoxin avoidance as a key intervention.
Renal Replacement Therapy
Action: renal replacement therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is renal replacement therapy (NCIT:C126400). NCIT:C126400 is a clinical intervention from the NCI Thesaurus. Ontology label: Renal Replacement Therapy NCIT:C126400
Initiation of dialysis (intermittent hemodialysis or continuous renal replacement therapy) for severe AKI with refractory fluid overload, hyperkalemia, or uremia. The optimal timing of RRT initiation remains an area of active investigation.
Show evidence (1 reference)
PMID:32397637 SUPPORT Human Clinical
"No specific treatment has been defined yet, and renal replacement therapy (RRT) remains the cornerstone supportive therapy for the most severe cases."
RRT is the primary supportive therapy for severe sepsis-associated AKI, though optimal timing of initiation remains debated.
AKI Care Bundles
Action: supportive careNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is supportive care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. Ontology label: Supportive Care NCIT:C15747
Standardized care bundles including fluid optimization, medication review, monitoring, and nephrology referral to improve early detection and management of hospital-acquired AKI.
Show evidence (1 reference)
PMID:29188454 SUPPORT Human Clinical
"Overall, a combination of e-alerts and AKI bundles supported by education yielded the most effective and statistically significant results."
Multicomponent AKI care bundles combining electronic alerts, standardized protocols, and education provide the most effective improvements in AKI outcomes.
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Environmental Factors

4
Nephrotoxic Drug Exposure
nephrotoxic drug exposure XCO:0001112 Experimental Conditions Ontology (XCO) Relation: this environmental factor is this exposure This environmental factor is nephrotoxic drug exposure, annotated with nephrotoxic chemical (XCO:0001112). XCO:0001112 is an exposure from the Experimental Conditions Ontology. healthcare facility ENVO:03501134 Environment Ontology (ENVO) Relation: this environmental factor occurs in this environment This environmental factor occurs in healthcare facility (ENVO:03501134). ENVO:03501134 is an environment from the Environment Ontology.
Exposure to nephrotoxic medications during hospitalization including aminoglycosides, vancomycin, NSAIDs, and ACE inhibitors is a major modifiable risk factor for hospital-acquired AKI.
Show evidence (2 references)
PMID:34537763 SUPPORT Human Clinical
"Nephrotoxic drug exposure and HA-AKI incidence were associated with an increased in-hospital mortality risk."
Nephrotoxic drug exposure is independently associated with both HA-AKI incidence and mortality.
PMID:26231194 SUPPORT Human Clinical
"About 40% of AKI cases were possibly drug-related and 16% may have been induced by Chinese traditional medicines or remedies."
Drug-related causes account for a large proportion of hospital-acquired AKI cases.
Mechanism Target:
TRIGGERS Nephrotoxic Injury — The node names aminoglycosides, vancomycin and NSAIDs in its own text and describes them causing direct tubular cell damage, so the exposure reaches it with nothing in between. Both items are graded partial because neither measures tubular injury: one reports the mortality associated with exposure and the other the fraction of cases attributable to drugs. This node is the entry's conformer to the drug_induced_nephrotoxicity module, which models the same uptake-to-cell-death chain in full.
Show evidence (2 references)
PMID:34537763 SUPPORT Human Clinical
"Nephrotoxic drug exposure and HA-AKI incidence were associated with an increased in-hospital mortality risk."
Associates nephrotoxic drug exposure with both incidence of the disorder and in-hospital mortality. An outcome measure rather than a measure of tubular injury.
PMID:26231194 SUPPORT Human Clinical
"About 40% of AKI cases were possibly drug-related and 16% may have been induced by Chinese traditional medicines or remedies."
About 40% of cases were possibly drug-related. An attributable fraction, which sizes the exposure without observing what it does to the tubule.
Contrast Media Exposure
healthcare facility ENVO:03501134 Environment Ontology (ENVO) Relation: this environmental factor occurs in this environment This environmental factor occurs in healthcare facility (ENVO:03501134). ENVO:03501134 is an environment from the Environment Ontology.
Intra-arterial or intravenous administration of iodinated contrast media for diagnostic or interventional procedures is a well-established cause of hospital-acquired AKI.
Show evidence (1 reference)
PMID:29802583 SUPPORT Human Clinical
"Pre-existing CKD, intra-arterial administration and CM volume are the most important risk factors for CI-AKI."
Identifies key risk factors for contrast-induced AKI, establishing contrast media as a significant cause of hospital-acquired AKI.
Mechanism Target:
TRIGGERS Nephrotoxic Injury — Contrast media are named at this node alongside the nephrotoxic drugs, and graded identically to them. The one available sentence reports the risk factors for contrast-induced kidney injury, which presupposes the entity rather than demonstrating it, so the evidence stays partial while the link itself rests on the node's own wording.
Show evidence (1 reference)
PMID:29802583 SUPPORT Human Clinical
"Pre-existing CKD, intra-arterial administration and CM volume are the most important risk factors for CI-AKI."
Names pre-existing kidney disease, intra-arterial administration and contrast volume as the leading risk factors. It grades severity within an already-assumed entity rather than tying contrast to tubular injury.
Sepsis
intensive care unit ENVO:03600008 Environment Ontology (ENVO) Relation: this environmental factor occurs in this environment This environmental factor occurs in intensive care unit (ENVO:03600008). ENVO:03600008 is an environment from the Environment Ontology.
Sepsis is the leading cause of AKI in critically ill hospitalized patients, with up to 60% of sepsis patients developing AKI.
Show evidence (1 reference)
PMID:33494815 SUPPORT Human Clinical
"Up to 60% of patients with sepsis develop acute kidney injury (AKI), which is associated with a poor clinical outcome."
Establishes sepsis as a major environmental trigger for hospital-acquired AKI in critically ill patients.
Mechanism Target:
TRIGGERS Sepsis-Associated AKI — The node is sepsis-associated kidney injury, so this exposure and this node are the same claim seen from two sides, and the cited sentence lands squarely on it by reporting how often sepsis is followed by kidney injury.
Show evidence (1 reference)
PMID:33494815 SUPPORT Human Clinical
"Up to 60% of patients with sepsis develop acute kidney injury (AKI), which is associated with a poor clinical outcome."
Reports that up to 60% of patients with sepsis develop acute kidney injury, which is this node's own event rather than a downstream consequence of it.
TRIGGERS Mitochondrial Dysfunction — A second edge from the same exposure, one step further in. The node describes mitochondrial damage and reduced mitochondrial mass in renal tubular cells, particularly in sepsis, and the same study measured exactly those two things in post-mortem kidney biopsies from affected patients. Recorded with known intermediates rather than as direct because the sepsis-associated injury node sits between the exposure and this one and is drawn explicitly here.
Show evidence (1 reference)
PMID:33494815 SUPPORT Human Clinical
"Compared to control subjects, sepsis-AKI patients had upregulated mRNA expression of oxidative damage markers, excess mitochondrial DNA damage and lower mitochondrial mass"
Measures oxidative DNA damage and reduced mitochondrial mass in patient kidney tissue, which is this node's own content stated almost word for word.
Major Surgery
surgical procedure exposure ECTO:2000054 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is surgical procedure exposure, annotated with exposure to surgery (ECTO:2000054). ECTO:2000054 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology. healthcare facility ENVO:03501134 Environment Ontology (ENVO) Relation: this environmental factor occurs in this environment This environmental factor occurs in healthcare facility (ENVO:03501134). ENVO:03501134 is an environment from the Environment Ontology.
Major surgical procedures, particularly cardiac and vascular surgery, are associated with perioperative hemodynamic instability and ischemia-reperfusion injury leading to AKI.
Show evidence (1 reference)
PMID:25057935 SUPPORT Human Clinical
"Multi-hit mechanisms (ischemia, inflammation, toxins) co-act on patients' predisposition (susceptibility)."
Describes the multi-hit model of postoperative AKI involving ischemia, inflammation, and nephrotoxins.
Mechanism Target:
TRIGGERS Ischemic Tubular Injury — The node names major surgery in its own text as a source of renal hypoperfusion leading to ischemia-reperfusion injury, with hypoperfusion as the intervening step. Graded partial because the cited sentence describes the multi-hit model in general terms and names ischemia among the hits without naming surgery, taking its surgical context from the paper's subject rather than from the sentence.
Show evidence (1 reference)
PMID:25057935 SUPPORT Human Clinical
"Multi-hit mechanisms (ischemia, inflammation, toxins) co-act on patients' predisposition (susceptibility)."
Describes ischemia, inflammation and toxins co-acting on a patient's predisposition. It names the ischemic mechanism at this node but not the exposure, which is why this is partial.
🔬

Diagnosis

3
Serum Creatinine Monitoring
Serial measurement of serum creatinine to detect acute rises per KDIGO criteria (≥0.3 mg/dL within 48h or ≥1.5x baseline within 7 days).
Show evidence (2 references)
PMID:23499048 SUPPORT Human Clinical
"The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI."
Serum creatinine is the primary biochemical parameter used in the KDIGO definition and staging system for AKI.
PMID:33556265 SUPPORT Human Clinical
"Despite advancements in standardizing the criteria for acute kidney injury (AKI), its definition remains based on changes in serum creatinine and urinary output that do not specifically represent tubular function or injury and that have significant limitations in the acute hospital setting."
While creatinine is the standard diagnostic marker, it is a late indicator of injury and has recognized limitations in the acute setting.
Urine Output Monitoring
Measurement of hourly urine output to detect oliguria (<0.5 mL/kg/h for 6h) as a KDIGO diagnostic criterion.
Show evidence (1 reference)
PMID:35685550 SUPPORT Human Clinical
"HA-AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria."
KDIGO criteria include both creatinine-based and urine-output-based definitions for AKI diagnosis.
Novel Biomarkers (NGAL, KIM-1, TIMP-2, IGFBP7)
Emerging urinary and plasma biomarkers that detect tubular injury earlier than serum creatinine. NGAL is released from the distal tubule, KIM-1 from the proximal tubule, and the [TIMP-2]·[IGFBP7] product (NephroCheck) is FDA-approved for AKI risk assessment.
These biomarkers can localize specific segments of injured tubules and predict AKI-to-CKD transition.
Show evidence (2 references)
PMID:33556265 SUPPORT Human Clinical
"Urinary kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), insulin-like growth factor-binding protein-7 (IGFBP-7), and tissue inhibitor of metalloprotease-2 (TIMP-2) are released from the proximal tubule while uromodulin (UMOD) is secreted from the loop of Henle..."
Multiple urinary biomarkers can localize tubular injury to specific nephron segments and provide earlier detection than serum creatinine.
PMID:39298548 SUPPORT Human Clinical
"Emerging biomarkers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and soluble tumor necrosis factor receptors (TNFRs) show promise in early detection and monitoring of disease progression."
KIM-1, NGAL, and TNFRs demonstrate promise for early AKI detection and monitoring progression from AKI to CKD.
📈

Progression

3
Acute injury phase (0-7 days)
Onset of tubular epithelial cell injury through ischemia, nephrotoxicity, or sepsis-associated microvascular dysfunction. Characterized by rising serum creatinine, declining urine output, and activation of regulated cell death pathways (apoptosis, necroptosis, ferroptosis, pyroptosis).
Show evidence (1 reference)
PMID:31005270 SUPPORT Model Organism
"Tubular cell death by necrosis and apoptosis is a central feature of renal IRI. Recent research has challenged traditional views of cell death by identifying new pathways in which cells die in a regulated manner but with the morphologic features of necrosis."
The acute phase is dominated by tubular cell death through both apoptotic and regulated necrosis pathways.
Acute kidney disease (AKD) window (7-90 days)
Period where maladaptive repair mechanisms may drive transition to chronic disease. Key processes include cell-cycle arrest, persistent inflammation, mitochondrial dysfunction, metabolic reprogramming, and pericyte-to-myofibroblast transition. This window represents a critical opportunity for intervention.
Show evidence (2 references)
PMID:33073587 SUPPORT Model Organism
"Recent research has suggested that damage to mitochondrial function in early AKI is a crucial factor leading to tubular injury and persistent renal insufficiency."
Mitochondrial dysfunction during the AKD window drives persistent tubular injury and incomplete recovery.
PMID:25810494 SUPPORT Model Organism
"recent studies show that a subpopulation of dedifferentiated, proliferating tubules recovering from AKI undergo pathologic growth arrest, fail to redifferentiate, and become atrophic."
Failed tubule recovery through pathologic growth arrest and dedifferentiation is a key mechanism during the AKD window that drives progression.
AKI-to-CKD transition (>90 days)
Patients who fail to recover renal function develop progressive fibrosis, capillary rarefaction, and chronic inflammation leading to CKD. Risk factors include AKI severity, duration, recurrent episodes, pre-existing CKD, diabetes, and older age.
Show evidence (2 references)
PMID:39298548 SUPPORT Human Clinical
"AKI often progresses to CKD due to maladaptive repair processes, persistent inflammation, and fibrosis, with both conditions sharing common pathways involving cell death, inflammation, and extracellular matrix (ECM) deposition."
AKI and CKD share overlapping pathophysiological mechanisms, with maladaptive repair driving the transition from acute injury to chronic disease.
PMID:37762322 SUPPORT Human Clinical
"Risk factors mentioned in AKI progression to CKD are frequency and severity of kidney injury, chronic diseases such as uncontrolled hypertension, diabetes mellitus, obesity and unmodifiable risk factors (i.e., genetics, older age or gender)."
Multiple clinical risk factors including AKI severity, comorbidities, and genetic predisposition determine the likelihood of AKI-to-CKD transition.
🪜

Stages

3
KDIGO Stage 1
Mild AKI defined by serum creatinine increase of ≥0.3 mg/dL (26.5 µmol/L) within 48 hours OR increase to ≥1.5-1.9 times baseline within 7 days OR urine output <0.5 mL/kg/h for 6-12 hours.
Show evidence (2 references)
PMID:23499048 SUPPORT Human Clinical
"The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI."
The KDIGO staging system represents harmonized consensus criteria for defining and staging AKI severity, with Stage 1 as the mildest category.
PMID:35685550 SUPPORT Human Clinical
"HA-AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria."
KDIGO criteria are the standard used to define and stage hospital-acquired AKI in clinical studies.
KDIGO Stage 2
Moderate AKI defined by serum creatinine increase to 2.0-2.9 times baseline OR urine output <0.5 mL/kg/h for ≥12 hours.
Show evidence (1 reference)
PMID:23499048 SUPPORT Human Clinical
"While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States."
KDIGO Stage 2 criteria are endorsed for epidemiological and clinical trial use, though the panel noted limitations for direct clinical application.
KDIGO Stage 3
Severe AKI defined by serum creatinine increase to ≥3.0 times baseline OR increase to ≥4.0 mg/dL (353.6 µmol/L) OR initiation of renal replacement therapy OR urine output <0.3 mL/kg/h for ≥24 hours OR anuria for ≥12 hours. In patients <18 years, decrease in eGFR to <35 mL/min/1.73 m².
Show evidence (2 references)
PMID:23499048 SUPPORT Human Clinical
"The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of..."
KDIGO Stage 3 represents the most severe category of AKI, often requiring renal replacement therapy, with limited evidence-based treatment options beyond supportive care.
PMID:32397637 SUPPORT Human Clinical
"No specific treatment has been defined yet, and renal replacement therapy (RRT) remains the cornerstone supportive therapy for the most severe cases."
Stage 3 AKI frequently requires initiation of RRT, which is one of the defining criteria for this stage.
📊

Prevalence

3
Hospitalized adults (general)
Point Prevalence 10000.0–25000.0 per 100,000 >1 in 1,000
Show evidence (1 reference)
PMID:20877177 SUPPORT Human Clinical
"Acute kidney injury (AKI) is a common clinical syndrome in hospitalized patients associated with high morbidity and mortality rates."
Establishes AKI as a common syndrome among hospitalized patients, consistent with reported incidence estimates of 10-25%.
ICU patients
Point Prevalence 16000.0–59000.0 per 100,000 >1 in 1,000
Show evidence (1 reference)
PMID:25845505 SUPPORT Model Organism
"Sepsis-induced AKI is diagnosed in up to 47% of human ICU patients and is seen as a major public health concern associated with increased mortality and increased progression to chronic kidney disease (CKD)."
Veterinary journal review citing human ICU data; up to 47% of ICU patients develop sepsis-associated AKI.
Elderly hospitalized patients
Point Prevalence 15000.0–30000.0 per 100,000 >1 in 1,000
Higher incidence in older adults due to reduced renal reserve, comorbidities, and polypharmacy
Show evidence (1 reference)
PMID:34537763 SUPPORT Human Clinical
"In the HA-AKI group, the proportion of patients with prior use of drugs with possible nephrotoxicity was higher than that of patients with prior use of drugs with identified nephrotoxicity (p < 0.05)."
Elderly patients are disproportionately affected by nephrotoxic drug-related HA-AKI due to polypharmacy and reduced renal reserve.
🌍

Epidemiology

3
ICU HA-AKI incidence
Incidence of hospital-acquired AKI among critically ill patients admitted to ICU without AKI on admission.
16–59
ICU prospective cohort data report 16.1% HA-AKI incidence with hospital mortality of 43.2% in affected patients.
Show evidence (1 reference)
PMID:25845505 SUPPORT Model Organism
"Sepsis-induced AKI is diagnosed in up to 47% of human ICU patients and is seen as a major public health concern associated with increased mortality and increased progression to chronic kidney disease (CKD)."
Veterinary journal review citing human ICU data on high AKI incidence in sepsis.
ICU HA-AKI mortality
In-hospital mortality in patients who develop AKI during ICU stay.
30–45
Mortality rates for ICU-acquired AKI are substantially higher than for patients without AKI (14% vs 43%).
Show evidence (1 reference)
PMID:20877177 SUPPORT Human Clinical
"Acute kidney injury (AKI) is a common clinical syndrome in hospitalized patients associated with high morbidity and mortality rates."
Confirms AKI is associated with high mortality rates in hospitalized patients.
Under-recognition rate
Proportion of AKI episodes not formally diagnosed or coded during hospitalization.
55–70
Studies report that 57-66% of creatinine-defined AKI episodes lack administrative documentation, contributing to delayed intervention.
Show evidence (1 reference)
PMID:24075024 SUPPORT Human Clinical
"Formal documentation of AKI occurred in 2,325 patients (43%)."
In a cohort of 5,438 adults with creatinine-defined AKI across three hospitals, only 43% had formal documentation, meaning 57% of AKI episodes were unrecognized in billing codes.
📊

Related Datasets

2
Elevated FTO alleviates sepsis-induced acute kidney injury by regulating macrophage inflammatory phenotypes [MeRIP-seq] geo:GSE297679
Recent studies have linked the dysregulation of N6-methyladenosine (m6A) to sepsis-induced acute kidney injury (SAKI), highlighting the persistent challenge of managing excessive proinflammatory cytokine production and subsequent organ dysfunction. In this study, we analyzed the dataset GSE32707 and GSE69063, fat mass and obesity-associated protein (FTO) was identified as the sole gene exhibiting significant downregulation within the transcriptome of peripheral blood samples from sepsis patients among m6A-related proteins.
mouse BULK RNA SEQ n=12
PMID:41235650
Identified by GEO DataSets index search for Hospital-Acquired Acute Kidney Injury (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
Spatial profiling of hypoxic injury in human kidney organoids geo:GSE307588
This dataset relates to a spatial transcriptomic experiment investigating potential reparative and inflammatory roles for macrophages in human iPSC-derived kidney organoids exposed to hypoxic injury, linked to a broader study of ischaemic kidney injury and repair in this model (https://doi.org/10.1101/2023.10.04.558359). Acute kidney injury (AKI) is a common clinical disorder linked to high rates of illness and death. Ischaemia is a leading cause of AKI, where reduced blood flow to the kidney triggers hypoxia and cell death in the nephron epithelium, impairing essential fluid handling and waste removal functions.
human SPATIAL TRANSCRIPTOMICS n=25
Identified by GEO DataSets index search for Hospital-Acquired Acute Kidney Injury (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
🔬

Clinical Trials

1
NCT02568722 PHASE_III COMPLETED
STARRT-AKI trial: multinational randomized controlled trial comparing accelerated versus standard initiation of renal-replacement therapy in critically ill patients with severe AKI. The accelerated strategy initiated RRT within 12 hours of eligibility versus a standard strategy where RRT was discouraged unless conventional indications developed or AKI persisted >72 hours. Found no mortality benefit with accelerated initiation and higher adverse event rates.
Target Phenotypes: Acute kidney injury HP:0001919 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Acute kidney injury (HP:0001919). HP:0001919 is a phenotype from the Human Phenotype Ontology. Oliguria HP:0100520 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Oliguria (HP:0100520). HP:0100520 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32668114 SUPPORT Human Clinical
"Among critically ill patients with acute kidney injury, an accelerated renal-replacement strategy was not associated with a lower risk of death at 90 days than a standard strategy."
This landmark trial of 2927 critically ill AKI patients demonstrated no mortality benefit of accelerated vs standard RRT initiation, with 43.9% vs 43.7% 90-day mortality respectively.
{ }

Source YAML

click to show 
name: Hospital-Acquired Acute Kidney Injury
creation_date: "2026-03-09T12:00:00Z"
category: Complex
parents:
- Renal Disease
disease_term:
  preferred_term: hospital-acquired acute kidney injury
  term:
    id: MONDO:0002492
    label: acute kidney injury
description: >
  Hospital-acquired acute kidney injury (HA-AKI) is a common and serious
  clinical syndrome defined as AKI developing after hospital admission,
  typically diagnosed using KDIGO serum creatinine and urine output criteria.
  It represents a convergent endpoint arising from overlapping inpatient insults
  including sepsis, nephrotoxic drug exposure, perioperative hemodynamic
  instability, and contrast media administration. HA-AKI affects 10-25% of
  hospitalized patients overall and up to 50-60% of ICU patients, with
  in-hospital mortality rates of 30-45% for ICU-acquired cases. Despite
  advances in recognition and supportive care, effective preventive and
  therapeutic strategies remain limited, and HA-AKI is an independent risk
  factor for progression to chronic kidney disease.
has_subtypes:
- name: Sepsis-Associated AKI
  description: >
    AKI developing as a complication of sepsis in hospitalized patients,
    driven by systemic inflammation, microvascular dysfunction, and tubular cell injury.
- name: Nephrotoxic AKI
  description: >
    AKI caused by exposure to nephrotoxic agents including aminoglycosides,
    contrast media, NSAIDs, and vancomycin during hospitalization.
- name: Postoperative AKI
  description: >
    AKI developing after major surgery, particularly cardiac, vascular, or
    abdominal procedures, due to perioperative hemodynamic instability and ischemia.
- name: Contrast-Induced AKI
  description: >
    AKI following intra-arterial or intravenous administration of iodinated
    contrast media for diagnostic or interventional procedures.
pathophysiology:
- name: Ischemic Tubular Injury
  description: >
    Renal hypoperfusion from sepsis, major surgery, or hemodynamic instability
    causes ischemia-reperfusion injury to tubular epithelial cells, leading to
    acute tubular necrosis (ATN), the most common cause of hospital-acquired AKI.
    Tubular cell death occurs through regulated necrosis pathways including
    necroptosis and ferroptosis, with subsequent release of cytosolic components
    that amplify inflammation.
  locations:
  - preferred_term: Proximal Tubule
    term:
      id: UBERON:0004134
      label: proximal tubule
  - preferred_term: Renal Tubule
    term:
      id: UBERON:0009773
      label: renal tubule
  cell_types:
  - preferred_term: Proximal Tubular Epithelial Cell
    term:
      id: CL:0002306
      label: epithelial cell of proximal tubule
  - preferred_term: Peritubular Capillary Endothelial Cell
    term:
      id: CL:1001033
      label: peritubular capillary endothelial cell
  biological_processes:
  - preferred_term: Ischemic Response
    term:
      id: GO:0002931
      label: response to ischemia
  - preferred_term: Programmed Necrotic Cell Death
    term:
      id: GO:0097300
      label: programmed necrotic cell death
  - preferred_term: Apoptotic Process
    term:
      id: GO:0006915
      label: apoptotic process
  evidence:
  - reference: PMID:31005270
    reference_title: "Regulated necrosis in kidney ischemia-reperfusion injury."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Tubular cell death by necrosis and apoptosis is a central feature of renal IRI. Recent research has challenged traditional views of cell death by identifying new pathways in which cells die in a regulated manner but with the morphologic features of necrosis."
    explanation: Demonstrates that regulated necrosis (necroptosis and ferroptosis) alongside apoptosis are central mechanisms of tubular injury in renal ischemia-reperfusion.
  - reference: PMID:25057935
    reference_title: "Postoperative acute kidney injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Acute kidney injury (AKI) represents 18-47% of all causes of hospital-acquired AKI and it is associated with a high incidence of morbidity and mortality especially in patients requiring dialysis."
    explanation: Postoperative AKI is a major contributor to hospital-acquired AKI, confirming ischemic tubular injury as a predominant mechanism.
- name: Nephrotoxic Injury
  conforms_to: "drug_induced_nephrotoxicity#Proximal Tubular Epithelial Cell Death"
  description: >
    Exposure to nephrotoxic agents such as aminoglycosides, contrast media,
    NSAIDs, and vancomycin causes direct tubular cell damage and apoptosis,
    contributing to a significant proportion of hospital-acquired AKI cases.
    Contrast-induced AKI is the third leading cause of hospital-acquired AKI.
    The drug-induced arm conforms to the conserved drug_induced_nephrotoxicity
    module: nephrotoxin uptake by proximal tubular cells drives oxidative and
    mitochondrial injury, converging here on tubular epithelial cell death.
  locations:
  - preferred_term: Proximal Tubule
    term:
      id: UBERON:0004134
      label: proximal tubule
  cell_types:
  - preferred_term: Proximal Tubular Epithelial Cell
    term:
      id: CL:0002306
      label: epithelial cell of proximal tubule
  biological_processes:
  - preferred_term: Apoptotic Process
    term:
      id: GO:0006915
      label: apoptotic process
  - preferred_term: Response to Oxidative Stress
    term:
      id: GO:0006979
      label: response to oxidative stress
  evidence:
  - reference: PMID:29802583
    reference_title: "Contrast medium induced acute kidney injury: a narrative review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Contrast-induced acute kidney injury (CI-AKI) is the third leading cause of hospital-acquired acute kidney injury."
    explanation: Confirms that contrast media nephrotoxicity is a major contributor to hospital-acquired AKI.
  - reference: PMID:34537763
    reference_title: "Hospital-Acquired Acute Kidney Injury in Older Patients: Clinical Characteristics and Drug Analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In the HA-AKI group, the proportion of patients with prior use of drugs with possible nephrotoxicity was higher than that of patients with prior use of drugs with identified nephrotoxicity (p < 0.05)."
    explanation: Demonstrates that nephrotoxic drug exposure is a key risk factor for hospital-acquired AKI in older patients.
- name: Sepsis-Associated AKI
  description: >
    Systemic inflammation during sepsis triggers a complex interplay of
    microvascular dysfunction, inflammatory mediator release, and tubular
    cell injury through both ischemic and non-ischemic pathways. Recent evidence
    shows renal blood flow may be normal or increased in early sepsis-AKI,
    suggesting microvascular and inflammatory mechanisms predominate over
    global hypoperfusion.
  locations:
  - preferred_term: Renal Glomerulus
    term:
      id: UBERON:0000074
      label: renal glomerulus
  - preferred_term: Kidney Vasculature
    term:
      id: UBERON:0006544
      label: kidney vasculature
  cell_types:
  - preferred_term: Glomerular Endothelial Cell
    term:
      id: CL:0002188
      label: glomerular endothelial cell
  - preferred_term: Kidney Resident Macrophage
    term:
      id: CL:1000698
      label: kidney resident macrophage
  - preferred_term: Proximal Tubular Epithelial Cell
    term:
      id: CL:0002306
      label: epithelial cell of proximal tubule
  biological_processes:
  - preferred_term: Inflammatory Response
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: Cell Death
    term:
      id: GO:0008219
      label: cell death
  evidence:
  - reference: PMID:29273917
    reference_title: "Recent advances in the pathogenetic mechanisms of sepsis-associated acute kidney injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "increasing importance is now attributed to kidney damage resulting from a complex interaction between immunologic mechanisms, inflammatory cascade activation, and deranged coagulation pathways, leading to microvascular dysfunction, endothelial damage, leukocyte/platelet activation with the formation of micro-thrombi, epithelial tubular cell injury and dysfunction."
    explanation: Describes the multifactorial pathogenesis of sepsis-associated AKI involving inflammation, coagulation, microvascular dysfunction, and tubular injury.
  - reference: PMID:33494815
    reference_title: "Sepsis is associated with mitochondrial DNA damage and a reduced mitochondrial mass in the kidney of patients with sepsis-AKI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Up to 60% of patients with sepsis develop acute kidney injury (AKI), which is associated with a poor clinical outcome."
    explanation: Documents the high incidence of AKI in sepsis patients and its association with poor outcomes, supporting sepsis as a major driver of hospital-acquired AKI.
  - reference: PMID:25845505
    reference_title: "Acute kidney injury in severe sepsis: pathophysiology, diagnosis, and treatment recommendations."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Sepsis-induced AKI is diagnosed in up to 47% of human ICU patients and is seen as a major public health concern associated with increased mortality and increased progression to chronic kidney disease (CKD)."
    explanation: Review published in a veterinary journal synthesizing human data on sepsis-induced AKI prevalence in ICU patients.
- name: Mitochondrial Dysfunction
  description: >
    Mitochondrial damage and reduced mitochondrial mass in renal tubular
    epithelial cells contribute to the pathogenesis of AKI, particularly in
    sepsis-associated cases. Oxidative DNA damage and impaired mitochondrial
    quality control pathways exacerbate tubular injury.
  cell_types:
  - preferred_term: Proximal Tubular Epithelial Cell
    term:
      id: CL:0002306
      label: epithelial cell of proximal tubule
  biological_processes:
  - preferred_term: Response to Oxidative Stress
    term:
      id: GO:0006979
      label: response to oxidative stress
  evidence:
  - reference: PMID:33494815
    reference_title: "Sepsis is associated with mitochondrial DNA damage and a reduced mitochondrial mass in the kidney of patients with sepsis-AKI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Compared to control subjects, sepsis-AKI patients had upregulated mRNA expression of oxidative damage markers, excess mitochondrial DNA damage and lower mitochondrial mass."
    explanation: Demonstrates that mitochondrial DNA damage and reduced mitochondrial mass are present in the kidneys of sepsis-AKI patients.
  - reference: PMID:26924060
    reference_title: "Autophagy in acute kidney injury."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Damaged mitochondria accumulate in autophagy-deficient kidneys of mice subjected to ischemia-reperfusion injury, but the precise mechanisms of regulation of mitophagy in AKI are not yet elucidated."
    explanation: Demonstrates that impaired mitophagy leads to accumulation of damaged mitochondria in AKI, supporting mitochondrial dysfunction as a key pathogenic mechanism.
phenotypes:
- category: Genitourinary
  name: Oliguria
  description: Reduced urine output below 0.5 mL/kg/hr, a hallmark clinical feature of AKI used in KDIGO staging criteria.
  phenotype_term:
    preferred_term: Oliguria
    term:
      id: HP:0100520
      label: Oliguria
  evidence:
  - reference: PMID:35685550
    reference_title: "Hospital-Acquired Acute Kidney Injury in Noncritical Care Setting: Clinical Characteristics and Outcomes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "HA-AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria."
    explanation: KDIGO criteria for AKI staging include oliguria as a key diagnostic feature alongside serum creatinine elevation.
- category: Genitourinary
  name: Elevated Serum Creatinine
  description: >
    Rise in serum creatinine of ≥0.3 mg/dL within 48 hours or ≥1.5 times
    baseline within 7 days, per KDIGO criteria. The defining biochemical
    hallmark of AKI.
  phenotype_term:
    preferred_term: Elevated Serum Creatinine
    term:
      id: HP:0003259
      label: Elevated circulating creatinine concentration
  evidence:
  - reference: PMID:26231194
    reference_title: "Epidemiology and Clinical Correlates of AKI in Chinese Hospitalized Adults."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "AKI was defined and staged according to Kidney Disease Improving Global Outcomes criteria."
    explanation: AKI diagnosis relies on serum creatinine elevation according to standardized KDIGO criteria.
- category: Metabolism
  name: Metabolic Acidosis
  description: >
    Impaired renal acid excretion leads to accumulation of metabolic acids
    and decreased serum bicarbonate.
  phenotype_term:
    preferred_term: Metabolic Acidosis
    term:
      id: HP:0001942
      label: Metabolic acidosis
  evidence:
  - reference: PMID:32397637
    reference_title: "Timing of Initiation of Renal Replacement Therapy in Sepsis-Associated Acute Kidney Injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Established and widely accepted indications for starting RRT include refractory fluid overload, severe hyperkalemia and metabolic acidosis refractory to medical therapy"
    explanation: Metabolic acidosis is a recognized complication of severe AKI requiring renal replacement therapy.
- category: Metabolism
  name: Hyperkalemia
  description: >
    Elevated serum potassium due to decreased renal excretion, posing risk
    of cardiac arrhythmias and a key indication for renal replacement therapy.
  phenotype_term:
    preferred_term: Hyperkalemia
    term:
      id: HP:0002153
      label: Hyperkalemia
  evidence:
  - reference: PMID:32397637
    reference_title: "Timing of Initiation of Renal Replacement Therapy in Sepsis-Associated Acute Kidney Injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Established and widely accepted indications for starting RRT include refractory fluid overload, severe hyperkalemia and metabolic acidosis refractory to medical therapy"
    explanation: Hyperkalemia is a life-threatening complication of AKI and one of the established indications for initiating RRT.
- category: Genitourinary
  name: Fluid Overload
  description: >
    Inability to excrete excess fluid leads to peripheral edema, pulmonary
    edema, and hypertension. A common complication of AKI that may require
    renal replacement therapy.
  phenotype_term:
    preferred_term: Edema
    term:
      id: HP:0000969
      label: Edema
  evidence:
  - reference: PMID:32397637
    reference_title: "Timing of Initiation of Renal Replacement Therapy in Sepsis-Associated Acute Kidney Injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Established and widely accepted indications for starting RRT include refractory fluid overload, severe hyperkalemia and metabolic acidosis refractory to medical therapy"
    explanation: Refractory fluid overload is a recognized complication of AKI and an indication for initiating renal replacement therapy.
- category: Genitourinary
  name: Azotemia
  description: >
    Accumulation of nitrogenous waste products (urea and creatinine) in the
    blood due to impaired renal clearance.
  phenotype_term:
    preferred_term: Azotemia
    term:
      id: HP:0002157
      label: Azotemia
  evidence:
  - reference: PMID:32397637
    reference_title: "Timing of Initiation of Renal Replacement Therapy in Sepsis-Associated Acute Kidney Injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Acute complications related to AKI are diverse and depend on the severity of the insult."
    explanation: Azotemia (accumulation of nitrogenous wastes) is a core feature of AKI driving uremic complications.
- category: Genitourinary
  name: Proteinuria
  description: >
    Presence of excess protein in urine due to tubular damage or glomerular
    dysfunction in AKI.
  phenotype_term:
    preferred_term: Proteinuria
    term:
      id: HP:0000093
      label: Proteinuria
  evidence:
  - reference: PMID:28927644
    reference_title: "Acute kidney injury is a risk factor for subsequent proteinuria."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "AKI is a risk factor for incident or worsening proteinuria, suggesting a possible mechanism linking AKI and future CKD."
    explanation: Large Veterans cohort study demonstrates that AKI causes new-onset or worsening proteinuria, with odds ratios of 1.20-1.39 across months of follow-up, and higher odds with more severe AKI stages.
environmental:
- name: Nephrotoxic Drug Exposure
  exposure_term:
    preferred_term: nephrotoxic drug exposure
    term:
      id: XCO:0001112
      label: nephrotoxic chemical
  influences_mechanisms:
  - target: Nephrotoxic Injury
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      The node names aminoglycosides, vancomycin and NSAIDs in its own text
      and describes them causing direct tubular cell damage, so the exposure
      reaches it with nothing in between. Both items are graded partial
      because neither measures tubular injury: one reports the mortality
      associated with exposure and the other the fraction of cases
      attributable to drugs. This node is the entry's conformer to the
      drug_induced_nephrotoxicity module, which models the same
      uptake-to-cell-death chain in full.
    evidence:
    - reference: PMID:34537763
      reference_title: "Hospital-Acquired Acute Kidney Injury in Older Patients: Clinical Characteristics and Drug Analysis."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Nephrotoxic drug exposure and HA-AKI incidence were associated with an increased in-hospital mortality risk."
      explanation: >-
        Associates nephrotoxic drug exposure with both incidence of the
        disorder and in-hospital mortality. An outcome measure rather than a
        measure of tubular injury.
    - reference: PMID:26231194
      reference_title: "Epidemiology and Clinical Correlates of AKI in Chinese Hospitalized Adults."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "About 40% of AKI cases were possibly drug-related and 16% may have been induced by Chinese traditional medicines or remedies."
      explanation: >-
        About 40% of cases were possibly drug-related. An attributable
        fraction, which sizes the exposure without observing what it does to
        the tubule.
  description: >
    Exposure to nephrotoxic medications during hospitalization including
    aminoglycosides, vancomycin, NSAIDs, and ACE inhibitors is a major
    modifiable risk factor for hospital-acquired AKI.
  environment_context:
    preferred_term: healthcare facility
    term:
      id: ENVO:03501134
      label: healthcare facility
  evidence:
  - reference: PMID:34537763
    reference_title: "Hospital-Acquired Acute Kidney Injury in Older Patients: Clinical Characteristics and Drug Analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Nephrotoxic drug exposure and HA-AKI incidence were associated with an increased in-hospital mortality risk."
    explanation: Nephrotoxic drug exposure is independently associated with both HA-AKI incidence and mortality.
  - reference: PMID:26231194
    reference_title: "Epidemiology and Clinical Correlates of AKI in Chinese Hospitalized Adults."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "About 40% of AKI cases were possibly drug-related and 16% may have been induced by Chinese traditional medicines or remedies."
    explanation: Drug-related causes account for a large proportion of hospital-acquired AKI cases.
- name: Contrast Media Exposure
  influences_mechanisms:
  - target: Nephrotoxic Injury
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      Contrast media are named at this node alongside the nephrotoxic drugs,
      and graded identically to them. The one available sentence reports the
      risk factors for contrast-induced kidney injury, which presupposes the
      entity rather than demonstrating it, so the evidence stays partial while
      the link itself rests on the node's own wording.
    evidence:
    - reference: PMID:29802583
      reference_title: "Contrast medium induced acute kidney injury: a narrative review."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Pre-existing CKD, intra-arterial administration and CM volume are the most important risk factors for CI-AKI."
      explanation: >-
        Names pre-existing kidney disease, intra-arterial administration and
        contrast volume as the leading risk factors. It grades severity within
        an already-assumed entity rather than tying contrast to tubular
        injury.
  description: >
    Intra-arterial or intravenous administration of iodinated contrast media
    for diagnostic or interventional procedures is a well-established cause
    of hospital-acquired AKI.
  environment_context:
    preferred_term: healthcare facility
    term:
      id: ENVO:03501134
      label: healthcare facility
  evidence:
  - reference: PMID:29802583
    reference_title: "Contrast medium induced acute kidney injury: a narrative review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Pre-existing CKD, intra-arterial administration and CM volume are the most important risk factors for CI-AKI."
    explanation: Identifies key risk factors for contrast-induced AKI, establishing contrast media as a significant cause of hospital-acquired AKI.
- name: Sepsis
  influences_mechanisms:
  - target: Sepsis-Associated AKI
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: >-
      The node is sepsis-associated kidney injury, so this exposure and this
      node are the same claim seen from two sides, and the cited sentence
      lands squarely on it by reporting how often sepsis is followed by kidney
      injury.
    evidence:
    - reference: PMID:33494815
      reference_title: "Sepsis is associated with mitochondrial DNA damage and a reduced mitochondrial mass in the kidney of patients with sepsis-AKI."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Up to 60% of patients with sepsis develop acute kidney injury (AKI), which is associated with a poor clinical outcome."
      explanation: >-
        Reports that up to 60% of patients with sepsis develop acute kidney
        injury, which is this node's own event rather than a downstream
        consequence of it.
  - target: Mitochondrial Dysfunction
    environmental_effect: TRIGGERS
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      A second edge from the same exposure, one step further in. The node
      describes mitochondrial damage and reduced mitochondrial mass in renal
      tubular cells, particularly in sepsis, and the same study measured
      exactly those two things in post-mortem kidney biopsies from affected
      patients. Recorded with known intermediates rather than as direct
      because the sepsis-associated injury node sits between the exposure and
      this one and is drawn explicitly here.
    evidence:
    - reference: PMID:33494815
      reference_title: "Sepsis is associated with mitochondrial DNA damage and a reduced mitochondrial mass in the kidney of patients with sepsis-AKI."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Compared to control subjects, sepsis-AKI patients had upregulated mRNA expression of oxidative damage markers, excess mitochondrial DNA damage and lower mitochondrial mass"
      explanation: >-
        Measures oxidative DNA damage and reduced mitochondrial mass in
        patient kidney tissue, which is this node's own content stated almost
        word for word.
  description: >
    Sepsis is the leading cause of AKI in critically ill hospitalized patients,
    with up to 60% of sepsis patients developing AKI.
  environment_context:
    preferred_term: intensive care unit
    term:
      id: ENVO:03600008
      label: intensive care unit
  evidence:
  - reference: PMID:33494815
    reference_title: "Sepsis is associated with mitochondrial DNA damage and a reduced mitochondrial mass in the kidney of patients with sepsis-AKI."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Up to 60% of patients with sepsis develop acute kidney injury (AKI), which is associated with a poor clinical outcome."
    explanation: Establishes sepsis as a major environmental trigger for hospital-acquired AKI in critically ill patients.
- name: Major Surgery
  exposure_term:
    preferred_term: surgical procedure exposure
    term:
      id: ECTO:2000054
      label: exposure to surgery
  influences_mechanisms:
  - target: Ischemic Tubular Injury
    environmental_effect: TRIGGERS
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      The node names major surgery in its own text as a source of renal
      hypoperfusion leading to ischemia-reperfusion injury, with hypoperfusion
      as the intervening step. Graded partial because the cited sentence
      describes the multi-hit model in general terms and names ischemia among
      the hits without naming surgery, taking its surgical context from the
      paper's subject rather than from the sentence.
    evidence:
    - reference: PMID:25057935
      reference_title: "Postoperative acute kidney injury."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Multi-hit mechanisms (ischemia, inflammation, toxins) co-act on patients' predisposition (susceptibility)."
      explanation: >-
        Describes ischemia, inflammation and toxins co-acting on a patient's
        predisposition. It names the ischemic mechanism at this node but not
        the exposure, which is why this is partial.
  description: >
    Major surgical procedures, particularly cardiac and vascular surgery,
    are associated with perioperative hemodynamic instability and
    ischemia-reperfusion injury leading to AKI.
  environment_context:
    preferred_term: healthcare facility
    term:
      id: ENVO:03501134
      label: healthcare facility
  evidence:
  - reference: PMID:25057935
    reference_title: "Postoperative acute kidney injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Multi-hit mechanisms (ischemia, inflammation, toxins) co-act on patients' predisposition (susceptibility)."
    explanation: Describes the multi-hit model of postoperative AKI involving ischemia, inflammation, and nephrotoxins.
treatments:
- name: Fluid Resuscitation
  description: >
    Intravenous fluid administration to restore renal perfusion in
    prerenal or ischemic AKI. Isotonic saline or balanced crystalloid
    solutions are the mainstay of volume expansion.
  treatment_term:
    preferred_term: fluid replacement therapy
    term:
      id: NCIT:C66896
      label: Hydration Therapy
  evidence:
  - reference: PMID:29802583
    reference_title: "Contrast medium induced acute kidney injury: a narrative review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The intravenous administration of moderate amounts of isotonic saline solution or bicarbonate solution still represents the principal intervention with documented and acceptable effectiveness for CI-AKI prevention."
    explanation: Volume expansion with isotonic fluids is the most established preventive and therapeutic measure for AKI.
- name: Nephrotoxin Avoidance
  description: >
    Identification and discontinuation of nephrotoxic medications to
    prevent further tubular injury. Includes medication review using
    electronic alert systems and AKI care bundles.
  treatment_term:
    preferred_term: nephrotoxin avoidance
    term:
      id: NCIT:C15900
      label: Lifestyle Therapy
  evidence:
  - reference: PMID:29188454
    reference_title: "A narrative review of the impact of interventions in acute kidney injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This review found that e-alerts have varying effects on mortality and AKI progression, but decrease the incidence of contrast-induced AKI. The use of AKI bundles delivers statistically significant improvements in mortality and AKI progression."
    explanation: Electronic alerts and AKI bundles that include nephrotoxin avoidance improve outcomes in hospital-acquired AKI.
  - reference: PMID:34537763
    reference_title: "Hospital-Acquired Acute Kidney Injury in Older Patients: Clinical Characteristics and Drug Analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "With the increase in the number of patients with continued use of drugs with possible nephrotoxicity after HA-AKI, the clinical outcomes showed a tendency to worsen (p < 0.001)."
    explanation: Continued nephrotoxic drug exposure after AKI onset worsens outcomes, supporting nephrotoxin avoidance as a key intervention.
- name: Renal Replacement Therapy
  description: >
    Initiation of dialysis (intermittent hemodialysis or continuous renal
    replacement therapy) for severe AKI with refractory fluid overload,
    hyperkalemia, or uremia. The optimal timing of RRT initiation remains
    an area of active investigation.
  treatment_term:
    preferred_term: renal replacement therapy
    term:
      id: NCIT:C126400
      label: Renal Replacement Therapy
  evidence:
  - reference: PMID:32397637
    reference_title: "Timing of Initiation of Renal Replacement Therapy in Sepsis-Associated Acute Kidney Injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "No specific treatment has been defined yet, and renal replacement therapy (RRT) remains the cornerstone supportive therapy for the most severe cases."
    explanation: RRT is the primary supportive therapy for severe sepsis-associated AKI, though optimal timing of initiation remains debated.
- name: AKI Care Bundles
  description: >
    Standardized care bundles including fluid optimization, medication review,
    monitoring, and nephrology referral to improve early detection and management
    of hospital-acquired AKI.
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:29188454
    reference_title: "A narrative review of the impact of interventions in acute kidney injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Overall, a combination of e-alerts and AKI bundles supported by education yielded the most effective and statistically significant results."
    explanation: Multicomponent AKI care bundles combining electronic alerts, standardized protocols, and education provide the most effective improvements in AKI outcomes.
prevalence:
- population: Hospitalized adults (general)
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_low: 10000.0
  rate_high: 25000.0
  percentage: 10-25%
  evidence:
  - reference: PMID:20877177
    reference_title: "Hospital-acquired acute kidney injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Acute kidney injury (AKI) is a common clinical syndrome in hospitalized patients associated with high morbidity and mortality rates."
    explanation: Establishes AKI as a common syndrome among hospitalized patients, consistent with reported incidence estimates of 10-25%.
- population: ICU patients
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_low: 16000.0
  rate_high: 59000.0
  percentage: 16-59%
  evidence:
  - reference: PMID:25845505
    reference_title: "Acute kidney injury in severe sepsis: pathophysiology, diagnosis, and treatment recommendations."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Sepsis-induced AKI is diagnosed in up to 47% of human ICU patients and is seen as a major public health concern associated with increased mortality and increased progression to chronic kidney disease (CKD)."
    explanation: Veterinary journal review citing human ICU data; up to 47% of ICU patients develop sepsis-associated AKI.
- population: Elderly hospitalized patients
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_low: 15000.0
  rate_high: 30000.0
  percentage: 15-30%
  notes: Higher incidence in older adults due to reduced renal reserve, comorbidities, and polypharmacy
  evidence:
  - reference: PMID:34537763
    reference_title: "Hospital-Acquired Acute Kidney Injury in Older Patients: Clinical Characteristics and Drug Analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In the HA-AKI group, the proportion of patients with prior use of drugs with possible nephrotoxicity was higher than that of patients with prior use of drugs with identified nephrotoxicity (p < 0.05)."
    explanation: Elderly patients are disproportionately affected by nephrotoxic drug-related HA-AKI due to polypharmacy and reduced renal reserve.
epidemiology:
- name: ICU HA-AKI incidence
  description: Incidence of hospital-acquired AKI among critically ill patients admitted to ICU without AKI on admission.
  minimum_value: 16
  maximum_value: 59
  notes: ICU prospective cohort data report 16.1% HA-AKI incidence with hospital mortality of 43.2% in affected patients.
  evidence:
  - reference: PMID:25845505
    reference_title: "Acute kidney injury in severe sepsis: pathophysiology, diagnosis, and treatment recommendations."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Sepsis-induced AKI is diagnosed in up to 47% of human ICU patients and is seen as a major public health concern associated with increased mortality and increased progression to chronic kidney disease (CKD)."
    explanation: Veterinary journal review citing human ICU data on high AKI incidence in sepsis.
- name: ICU HA-AKI mortality
  description: In-hospital mortality in patients who develop AKI during ICU stay.
  minimum_value: 30
  maximum_value: 45
  notes: Mortality rates for ICU-acquired AKI are substantially higher than for patients without AKI (14% vs 43%).
  evidence:
  - reference: PMID:20877177
    reference_title: "Hospital-acquired acute kidney injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Acute kidney injury (AKI) is a common clinical syndrome in hospitalized patients associated with high morbidity and mortality rates."
    explanation: Confirms AKI is associated with high mortality rates in hospitalized patients.
- name: Under-recognition rate
  description: Proportion of AKI episodes not formally diagnosed or coded during hospitalization.
  minimum_value: 55
  maximum_value: 70
  notes: Studies report that 57-66% of creatinine-defined AKI episodes lack administrative documentation, contributing to delayed intervention.
  evidence:
  - reference: PMID:24075024
    reference_title: "The impact of documentation of severe acute kidney injury on mortality."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Formal documentation of AKI occurred in 2,325 patients (43%)."
    explanation: In a cohort of 5,438 adults with creatinine-defined AKI across three hospitals, only 43% had formal documentation, meaning 57% of AKI episodes were unrecognized in billing codes.
stages:
- name: KDIGO Stage 1
  description: >
    Mild AKI defined by serum creatinine increase of ≥0.3 mg/dL (26.5 µmol/L)
    within 48 hours OR increase to ≥1.5-1.9 times baseline within 7 days OR
    urine output <0.5 mL/kg/h for 6-12 hours.
  evidence:
  - reference: PMID:23499048
    reference_title: "KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI."
    explanation: The KDIGO staging system represents harmonized consensus criteria for defining and staging AKI severity, with Stage 1 as the mildest category.
  - reference: PMID:35685550
    reference_title: "Hospital-Acquired Acute Kidney Injury in Noncritical Care Setting: Clinical Characteristics and Outcomes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "HA-AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria."
    explanation: KDIGO criteria are the standard used to define and stage hospital-acquired AKI in clinical studies.
- name: KDIGO Stage 2
  description: >
    Moderate AKI defined by serum creatinine increase to 2.0-2.9 times baseline
    OR urine output <0.5 mL/kg/h for ≥12 hours.
  evidence:
  - reference: PMID:23499048
    reference_title: "KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States."
    explanation: KDIGO Stage 2 criteria are endorsed for epidemiological and clinical trial use, though the panel noted limitations for direct clinical application.
- name: KDIGO Stage 3
  description: >
    Severe AKI defined by serum creatinine increase to ≥3.0 times baseline
    OR increase to ≥4.0 mg/dL (353.6 µmol/L) OR initiation of renal replacement
    therapy OR urine output <0.3 mL/kg/h for ≥24 hours OR anuria for ≥12 hours.
    In patients <18 years, decrease in eGFR to <35 mL/min/1.73 m².
  evidence:
  - reference: PMID:23499048
    reference_title: "KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI."
    explanation: KDIGO Stage 3 represents the most severe category of AKI, often requiring renal replacement therapy, with limited evidence-based treatment options beyond supportive care.
  - reference: PMID:32397637
    reference_title: "Timing of Initiation of Renal Replacement Therapy in Sepsis-Associated Acute Kidney Injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "No specific treatment has been defined yet, and renal replacement therapy (RRT) remains the cornerstone supportive therapy for the most severe cases."
    explanation: Stage 3 AKI frequently requires initiation of RRT, which is one of the defining criteria for this stage.
diagnosis:
- name: Serum Creatinine Monitoring
  description: Serial measurement of serum creatinine to detect acute rises per KDIGO criteria (≥0.3 mg/dL within 48h or ≥1.5x baseline within 7 days).
  evidence:
  - reference: PMID:23499048
    reference_title: "KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI."
    explanation: Serum creatinine is the primary biochemical parameter used in the KDIGO definition and staging system for AKI.
  - reference: PMID:33556265
    reference_title: "Current concepts and advances in biomarkers of acute kidney injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Despite advancements in standardizing the criteria for acute kidney injury (AKI), its definition remains based on changes in serum creatinine and urinary output that do not specifically represent tubular function or injury and that have significant limitations in the acute hospital setting."
    explanation: While creatinine is the standard diagnostic marker, it is a late indicator of injury and has recognized limitations in the acute setting.
- name: Urine Output Monitoring
  description: Measurement of hourly urine output to detect oliguria (<0.5 mL/kg/h for 6h) as a KDIGO diagnostic criterion.
  evidence:
  - reference: PMID:35685550
    reference_title: "Hospital-Acquired Acute Kidney Injury in Noncritical Care Setting: Clinical Characteristics and Outcomes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "HA-AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria."
    explanation: KDIGO criteria include both creatinine-based and urine-output-based definitions for AKI diagnosis.
- name: Novel Biomarkers (NGAL, KIM-1, TIMP-2, IGFBP7)
  description: >
    Emerging urinary and plasma biomarkers that detect tubular injury earlier
    than serum creatinine. NGAL is released from the distal tubule, KIM-1
    from the proximal tubule, and the [TIMP-2]·[IGFBP7] product (NephroCheck)
    is FDA-approved for AKI risk assessment.
  notes: These biomarkers can localize specific segments of injured tubules and predict AKI-to-CKD transition.
  evidence:
  - reference: PMID:33556265
    reference_title: "Current concepts and advances in biomarkers of acute kidney injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Urinary kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), insulin-like growth factor-binding protein-7 (IGFBP-7), and tissue inhibitor of metalloprotease-2 (TIMP-2) are released from the proximal tubule while uromodulin (UMOD) is secreted from the loop of Henle and neutrophil gelatinase-associated lipocalin (NGAL) is released from the distal tubule."
    explanation: Multiple urinary biomarkers can localize tubular injury to specific nephron segments and provide earlier detection than serum creatinine.
  - reference: PMID:39298548
    reference_title: "Transition from acute kidney injury to chronic kidney disease: mechanisms, models, and biomarkers."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Emerging biomarkers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and soluble tumor necrosis factor receptors (TNFRs) show promise in early detection and monitoring of disease progression."
    explanation: KIM-1, NGAL, and TNFRs demonstrate promise for early AKI detection and monitoring progression from AKI to CKD.
progression:
- phase: Acute injury phase (0-7 days)
  notes: >
    Onset of tubular epithelial cell injury through ischemia, nephrotoxicity,
    or sepsis-associated microvascular dysfunction. Characterized by rising
    serum creatinine, declining urine output, and activation of regulated
    cell death pathways (apoptosis, necroptosis, ferroptosis, pyroptosis).
  evidence:
  - reference: PMID:31005270
    reference_title: "Regulated necrosis in kidney ischemia-reperfusion injury."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Tubular cell death by necrosis and apoptosis is a central feature of renal IRI. Recent research has challenged traditional views of cell death by identifying new pathways in which cells die in a regulated manner but with the morphologic features of necrosis."
    explanation: The acute phase is dominated by tubular cell death through both apoptotic and regulated necrosis pathways.
- phase: Acute kidney disease (AKD) window (7-90 days)
  notes: >
    Period where maladaptive repair mechanisms may drive transition to chronic
    disease. Key processes include cell-cycle arrest, persistent inflammation,
    mitochondrial dysfunction, metabolic reprogramming, and pericyte-to-myofibroblast
    transition. This window represents a critical opportunity for intervention.
  evidence:
  - reference: PMID:33073587
    reference_title: "Mitochondrial dysfunction and the AKI-to-CKD transition."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Recent research has suggested that damage to mitochondrial function in early AKI is a crucial factor leading to tubular injury and persistent renal insufficiency."
    explanation: Mitochondrial dysfunction during the AKD window drives persistent tubular injury and incomplete recovery.
  - reference: PMID:25810494
    reference_title: "Failed Tubule Recovery, AKI-CKD Transition, and Kidney Disease Progression."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "recent studies show that a subpopulation of dedifferentiated, proliferating tubules recovering from AKI undergo pathologic growth arrest, fail to redifferentiate, and become atrophic."
    explanation: Failed tubule recovery through pathologic growth arrest and dedifferentiation is a key mechanism during the AKD window that drives progression.
- phase: AKI-to-CKD transition (>90 days)
  notes: >
    Patients who fail to recover renal function develop progressive fibrosis,
    capillary rarefaction, and chronic inflammation leading to CKD. Risk
    factors include AKI severity, duration, recurrent episodes, pre-existing
    CKD, diabetes, and older age.
  evidence:
  - reference: PMID:39298548
    reference_title: "Transition from acute kidney injury to chronic kidney disease: mechanisms, models, and biomarkers."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "AKI often progresses to CKD due to maladaptive repair processes, persistent inflammation, and fibrosis, with both conditions sharing common pathways involving cell death, inflammation, and extracellular matrix (ECM) deposition."
    explanation: AKI and CKD share overlapping pathophysiological mechanisms, with maladaptive repair driving the transition from acute injury to chronic disease.
  - reference: PMID:37762322
    reference_title: "Pathway from Acute Kidney Injury to Chronic Kidney Disease: Molecules Involved in Renal Fibrosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Risk factors mentioned in AKI progression to CKD are frequency and severity of kidney injury, chronic diseases such as uncontrolled hypertension, diabetes mellitus, obesity and unmodifiable risk factors (i.e., genetics, older age or gender)."
    explanation: Multiple clinical risk factors including AKI severity, comorbidities, and genetic predisposition determine the likelihood of AKI-to-CKD transition.
genetic:
- name: FTO
  gene_term:
    preferred_term: FTO
    term:
      id: hgnc:24678
      label: FTO
  association: Associated
  notes: Locus near FTO on chromosome 16 associated with AKI risk, likely mediated through obesity-related pathways.
  evidence:
  - reference: PMID:38797326
    reference_title: "Genome-wide association study of hospitalized patients and acute kidney injury."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "Two novel loci reached genome-wide significance in the meta-analysis: rs11642015 near the FTO locus on chromosome 16 (obesity traits) (odds ratio 1.07 (95% confidence interval, 1.05-1.09))"
    explanation: GWAS of 54,488 AKI patients identified FTO locus as significantly associated with AKI susceptibility, though the effect was attenuated after adjustment for BMI and diabetes.
- name: SHROOM3
  gene_term:
    preferred_term: SHROOM3
    term:
      id: hgnc:30422
      label: SHROOM3
  association: Associated
  notes: Locus near SHROOM3 on chromosome 4 associated with AKI protection, related to glomerular filtration barrier integrity.
  evidence:
  - reference: PMID:38797326
    reference_title: "Genome-wide association study of hospitalized patients and acute kidney injury."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "rs4859682 near the SHROOM3 locus on chromosome 4 (glomerular filtration barrier integrity) (odds ratio 0.95 (95% confidence interval, 0.93-0.96))."
    explanation: SHROOM3 locus reached genome-wide significance as a protective factor against AKI, with colocalization to previous kidney function studies.
- name: APOE
  gene_term:
    preferred_term: APOE
    term:
      id: hgnc:613
      label: APOE
  association: Associated
  notes: APO E e2/e3/e4 polymorphism was the only variant with replicated association across multiple early AKI genetic studies.
  evidence:
  - reference: PMID:19443624
    reference_title: "Searching for genes that matter in acute kidney injury: a systematic review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Only one polymorphism, APO E e2/e3/e4, had greater than one study showing a significant impact (P < 0.05) on AKI incidence."
    explanation: Systematic review of 16 AKI genetic studies found APOE as the only replicated genetic association across multiple studies.
- name: NR5A2
  gene_term:
    preferred_term: NR5A2
    term:
      id: hgnc:7984
      label: NR5A2
  association: Associated
  notes: Variants near NR5A2 gene showed suggestive association with sepsis-associated AKI at sub-genome-wide significance.
  evidence:
  - reference: PMID:39636799
    reference_title: "Genetic variants associated with sepsis-associated acute kidney injury."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "rs184516290 (chr1:199814965:G:A), near the NR5A2 gene, chr1:199805801:T:TA, also near the NR5A2 gene, and rs117313146 (chr15:31999784:G:C), near the CHRNA7 gene, were associated with S-AKI at the suggestive level in all three models presented."
    explanation: NR5A2 variants showed consistent suggestive association with sepsis-AKI but did not reach genome-wide significance threshold.
- name: CHRNA7
  gene_term:
    preferred_term: CHRNA7
    term:
      id: hgnc:1960
      label: CHRNA7
  association: Associated
  notes: Variant near CHRNA7 gene on chromosome 15 showed suggestive association with sepsis-associated AKI across multiple models.
  evidence:
  - reference: PMID:39636799
    reference_title: "Genetic variants associated with sepsis-associated acute kidney injury."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "rs184516290 (chr1:199814965:G:A), near the NR5A2 gene, chr1:199805801:T:TA, also near the NR5A2 gene, and rs117313146 (chr15:31999784:G:C), near the CHRNA7 gene, were associated with S-AKI at the suggestive level in all three models presented."
    explanation: CHRNA7 variant showed consistent suggestive association with sepsis-AKI across three models but did not reach genome-wide significance.
clinical_trials:
- name: NCT02568722
  phase: PHASE_III
  status: COMPLETED
  description: >
    STARRT-AKI trial: multinational randomized controlled trial comparing
    accelerated versus standard initiation of renal-replacement therapy in
    critically ill patients with severe AKI. The accelerated strategy initiated
    RRT within 12 hours of eligibility versus a standard strategy where RRT was
    discouraged unless conventional indications developed or AKI persisted >72
    hours. Found no mortality benefit with accelerated initiation and higher
    adverse event rates.
  target_phenotypes:
  - preferred_term: Acute kidney injury
    term:
      id: HP:0001919
      label: Acute kidney injury
  - preferred_term: Oliguria
    term:
      id: HP:0100520
      label: Oliguria
  evidence:
  - reference: PMID:32668114
    reference_title: "Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Among critically ill patients with acute kidney injury, an accelerated renal-replacement strategy was not associated with a lower risk of death at 90 days than a standard strategy."
    explanation: This landmark trial of 2927 critically ill AKI patients demonstrated no mortality benefit of accelerated vs standard RRT initiation, with 43.9% vs 43.7% 90-day mortality respectively.
datasets:
- accession: geo:GSE297679
  title: Elevated FTO alleviates sepsis-induced acute kidney injury by regulating macrophage inflammatory phenotypes [MeRIP-seq]
  description: Recent studies have linked the dysregulation of N6-methyladenosine (m6A) to sepsis-induced acute kidney injury (SAKI), highlighting the persistent challenge of managing excessive proinflammatory cytokine production and subsequent organ dysfunction. In this study, we analyzed the dataset GSE32707 and GSE69063, fat mass and obesity-associated protein (FTO) was identified as the sole gene exhibiting significant downregulation within the transcriptome of peripheral blood samples from sepsis patients among m6A-related proteins.
  organism:
    preferred_term: mouse
    term:
      id: NCBITaxon:10090
      label: Mus musculus
  data_type: BULK_RNA_SEQ
  sample_count: 12
  publication: PMID:41235650
  notes: Identified by GEO DataSets index search for Hospital-Acquired Acute Kidney Injury (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE307588
  title: Spatial profiling of hypoxic injury in human kidney organoids
  data_type: SPATIAL_TRANSCRIPTOMICS
  description: This dataset relates to a spatial transcriptomic experiment investigating potential reparative and inflammatory roles for macrophages in human iPSC-derived kidney organoids exposed to hypoxic injury, linked to a broader study of ischaemic kidney injury and repair in this model (https://doi.org/10.1101/2023.10.04.558359). Acute kidney injury (AKI) is a common clinical disorder linked to high rates of illness and death. Ischaemia is a leading cause of AKI, where reduced blood flow to the kidney triggers hypoxia and cell death in the nephron epithelium, impairing essential fluid handling and waste removal functions.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  sample_count: 25
  notes: Identified by GEO DataSets index search for Hospital-Acquired Acute Kidney Injury (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
📚

References & Deep Research

Deep Research

1
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Disease Pathophysiology Research Template
Edison Scientific Literature 56 citations 2026-03-11T00:54:52.856313

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 Pathophysiology Research Template

Target Disease

  • Disease Name: Hospital-Acquired Acute Kidney Injury
  • MONDO ID: (if available)
  • Category: Complex

Research Objectives

Please provide a comprehensive research report on the pathophysiology of Hospital-Acquired Acute Kidney Injury. Focus on the molecular and cellular mechanisms underlying disease progression.

Required Information

1. Core Pathophysiology

  • What are the primary pathophysiological mechanisms?
  • What molecular pathways are dysregulated?
  • What cellular processes are affected?

2. Key Molecular Players

  • Genes/Proteins: Which genes are causally involved or implicated?
  • Chemical Entities: What metabolites, drugs, or small molecules are relevant?
  • Cell Types: Which cell types are primarily affected?
  • Anatomical Locations: Which tissues/organs are involved?

3. Biological Processes (for GO annotation)

  • What biological processes (GO terms) are disrupted?
  • Consider: signaling pathways, metabolic processes, cellular responses, transport, etc.

4. Cellular Components

  • Where in the cell do key processes occur?
  • Consider: organelles, membrane compartments, extracellular space, etc.

5. Disease Progression

  • What is the sequence of events from initial trigger to clinical manifestation?
  • Are there distinct stages or phases?

6. Phenotypic Manifestations

  • What are the key clinical phenotypes?
  • How do they relate to the underlying mechanisms?

Citation Requirements

  • Cite primary literature (PMID preferred) for all mechanistic claims
  • Prioritize recent reviews and landmark papers
  • Include direct quotes where possible to support key statements

Output Format

Structure your response as a narrative that could be used to populate a disease knowledge base entry with: - Pathophysiology description - Gene/protein annotations with ontology terms (HGNC, GO) - Phenotype associations (HP terms) - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Evidence items with PMIDs

Comprehensive Research Report: Hospital-Acquired Acute Kidney Injury (HA-AKI) Pathophysiology (Molecular/Cellular)

Target disease

  • Disease name: Hospital-acquired acute kidney injury (HA-AKI; also termed in-hospital AKI, HAAKI)
  • MONDO ID: Not consistently represented as a distinct MONDO entity in the retrieved sources; mechanistic evidence is largely for acute kidney injury broadly.
  • Category: Complex, multifactorial syndrome occurring during hospitalization (e.g., ICU, ward, perioperative, sepsis, drug exposure).

1) Key concepts and definitions (current understanding)

1.1 Definition and case ascertainment

Hospital-acquired AKI is commonly operationalized as AKI that develops after hospital admission, often using an onset cutoff (e.g., >48 h) plus KDIGO creatinine/urine-output criteria; one ICU prospective cohort explicitly defined hospital-acquired AKI as AKI developing after 48 h (KDIGO creatinine-based) (https://doi.org/10.1038/s41598-024-79533-6; published Nov 2024) (havaldar2024epidemiologicalstudyof pages 1-2).

Large-scale hospital surveillance studies also distinguish AKI present at admission vs AKI peaking later during hospitalization, classifying “in-hospital” AKI by the time of peak creatinine after admission (https://doi.org/10.1093/ckj/sfae231; published Jul 2024) (esposito2024recognitionpatternsof pages 7-8).

1.2 Recognition gap as a core systems problem in HA-AKI

A major feature of HA-AKI is under-recognition in routine workflows. In a cohort of 56,820 hospitalized adults, serum-creatinine-defined AKI incidence was 24.5%, but most creatinine-defined cases lacked administrative documentation: 16.7% were “KDIGO-AKI” (AKI by creatinine but not coded) versus 3.3% “full-AKI” (meets creatinine criteria and coded), yielding ~68% undetection by discharge coding (https://doi.org/10.1093/ckj/sfae231; Jul 2024) (esposito2024recognitionpatternsof pages 1-2, esposito2024recognitionpatternsof pages 4-6).

This recognition gap matters because undetected AKI still associates with adverse outcomes (esposito2024recognitionpatternsof pages 1-2).

2) Core pathophysiology (molecular/cellular mechanisms)

HA-AKI is not a single disease entity; rather, it is a convergent clinical endpoint arising from overlapping insults (hemodynamic perturbations, infection/sepsis, nephrotoxins, hypoxia, surgery). Across settings, mechanistic convergence occurs at the level of:

2.1 Tubular epithelial stress/injury as a central node

Renal tubular epithelial cells (TECs)—particularly proximal tubules—are mitochondria-rich and metabolically demanding, and are highlighted as key vulnerable effectors in AKI (https://doi.org/10.1016/j.ebiom.2024.105294; published Sep 2024) (li2024renaltubularepithelial pages 1-2).

Adaptive repair after mild injury involves dedifferentiation, migration, proliferation, and redifferentiation; maladaptive repair links to failed regeneration and fibrosis. A schematic overview of these repair trajectories (resident progenitor vs scattered tubular cell phenotype, adaptive vs maladaptive repair leading to fibrosis) is provided in Figure 1 of Li et al. 2024 (li2024renaltubularepithelial media 407547cb).

2.2 Regulated cell-death programs in TECs (apoptosis, necroptosis, pyroptosis, ferroptosis, PANoptosis)

A 2024 eBioMedicine review synthesizes TEC death modalities as drivers of tubular damage and subsequent inflammation: - Apoptosis (caspase-mediated, comparatively non-inflammatory) (li2024renaltubularepithelial pages 2-3). - Necroptosis (RIPK-dependent, MLKL-mediated membrane rupture) promoting “necroinflammation,” immune activation, and impaired tubular regeneration (li2024renaltubularepithelial pages 2-3). - Pyroptosis (gasdermin pore formation) releasing DAMPs and inflammatory mediators (li2024renaltubularepithelial pages 2-3). - Ferroptosis (iron-dependent phospholipid peroxidation) emphasized as an important contributor across AKI models, with tubular-segment synchronized injury and protective effects of ferroptosis inhibition (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 11-12). - PANoptosis is described as an integrated program enabling simultaneous engagement of pyroptosis, apoptosis, and necroptosis via PANoptosome complexes (li2024renaltubularepithelial pages 1-2).

These death programs directly shape the inflammatory microenvironment of the kidney and influence whether repair is adaptive or fibrogenic (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial media 407547cb).

2.3 Innate immune sensing and inflammasome-linked injury

In sepsis-associated contexts (a major HA-AKI driver), a contemporary view is that macro-hemodynamics and total renal blood flow may be preserved, while microcirculatory dysfunction and endothelial activation drive focal hypoxia and injury (https://doi.org/10.7759/cureus.75992; published Dec 2024) (aguilar2024sepsisassociatedacutekidney pages 2-4).

Key inflammatory processes described include cytokine release (e.g., TNF-α, IL-1, IL-6, IL-8), leukocyte adhesion, glycocalyx degradation, microvascular thrombosis, capillary shunting, and oxidative stress/mitochondrial dysfunction (aguilar2024sepsisassociatedacutekidney pages 2-4).

2.4 Mitochondrial dysfunction and metabolic reprogramming

A persistent mechanistic theme in AKI-to-AKD/CKD evolution is mitochondrial dysfunction, metabolic reprogramming, and cell-cycle arrest. A 2023 AKD overview emphasizes tubular epithelial cell-cycle arrest, chronic inflammation, mitochondrial dysfunction, failed regeneration, metabolic reprogramming, and RAS activation as mechanisms linking AKI to later subacute/chronic disease (https://doi.org/10.23876/j.krcp.23.001; published Nov 2023) (kung2023acutekidneydisease pages 1-3).

A TEC-focused synthesis also highlights mitophagy/biogenesis regulators and metabolic nodes (e.g., AMPK, PGC-1α-regulated pathways, and mitochondrial quality control) as important modulators of injury/repair balance (li2024renaltubularepithelial pages 16-16).

3) Key molecular players, cell types, anatomical locations, and chemical entities

3.1 Key genes/proteins (examples with strong mechanistic positioning in retrieved sources)

  • Ferroptosis / redox: GPX4 (ferroptosis suppression), and system Xc− components discussed as protective via glutathione maintenance (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 1-2, li2024renaltubularepithelial pages 13-14).
  • Necroptosis: RIPK1, RIPK3, MLKL as central executors of necroptotic membrane rupture and inflammatory amplification (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 13-14).
  • Inflammasome / pyroptosis axis: NLRP3 (inflammasome activation) highlighted as a key inflammatory amplifier in TEC injury (li2024renaltubularepithelial pages 13-14, li2024renaltubularepithelial pages 16-16).
  • Tubular injury biomarker-receptor: KIM-1 (HGNC: HAVCR1) appears as a TEC injury marker and also functions in phagocytosis/uptake-related contexts (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 16-16).
  • Microcirculation / endothelial activation (process-level evidence): endothelial activation, leukocyte adhesion, glycocalyx degradation, and microthrombosis are emphasized in sepsis-AKI mechanisms (aguilar2024sepsisassociatedacutekidney pages 2-4).

3.2 Primary affected cell types (knowledge-base ready)

  • Renal tubular epithelial cells (proximal tubule emphasized), as primary injury/repair executors (li2024renaltubularepithelial pages 1-2, li2024renaltubularepithelial media 407547cb).
  • Endothelial cells / microvascular compartment driving regional hypoxia in sepsis-AKI contexts (aguilar2024sepsisassociatedacutekidney pages 2-4).
  • Immune cells (neutrophils, macrophages, lymphocytes) as cytokine sources and effectors of inflammation and repair (aguilar2024sepsisassociatedacutekidney pages 2-4, li2024renaltubularepithelial pages 11-12).
  • Pericytes / fibroblast lineage implicated in maladaptive repair and fibrosis during AKI-to-AKD transitions (kung2023acutekidneydisease pages 3-4).

3.3 Anatomical compartments

  • Renal tubules (proximal tubule and thick ascending limb segments are highlighted in TEC-centric injury models) (li2024renaltubularepithelial pages 1-2).
  • Renal microcirculation (glomerular and peritubular capillaries) as key sites of endothelial activation and perfusion heterogeneity in sepsis (aguilar2024sepsisassociatedacutekidney pages 2-4).
  • Renal interstitium as a locus for inflammatory infiltration and later fibrogenesis (kung2023acutekidneydisease pages 3-4, li2024renaltubularepithelial pages 2-3).

3.4 Chemical entities and exposures relevant to HA-AKI

Nephrotoxic drugs and combinations are common hospital triggers. - In ICU HA-AKI, colistin exposure was identified as a risk factor in a prospective cohort (havaldar2024epidemiologicalstudyof pages 1-2). - In non-critical medical inpatients, predictors included type 2 diabetes and combined vancomycin + proton pump inhibitors, with mechanistic notes linking vancomycin to proximal tubular oxidative stress and PPIs to immune-mediated AIN-type mechanisms (https://doi.org/10.2147/IJNRD.S454987; published Apr 2024) (mekonnen2024hospitalacquiredacutekidney pages 6-8, mekonnen2024hospitalacquiredacutekidney pages 1-2). - In a hospitalized cohort of AKI cases managed by an AKI-nephrology team, drug-induced AKI (DI-AKI) accounted for 19.3% of AKI, with a mechanistic taxonomy: ATN (77%), AIN (15.2%), and crystal-induced nephropathy (2.6%); vancomycin was a leading nephrotoxin and associated with higher AKST and death (https://doi.org/10.3389/fmed.2024.1459170; published Oct 29, 2024) (garcia2024druginducedacutekidney pages 1-2, garcia2024druginducedacutekidney pages 2-3, garcia2024druginducedacutekidney pages 3-5).

4) Biological processes disrupted (GO-oriented)

Mechanistic evidence from recent reviews supports disruption of the following process categories: - Regulated cell death (apoptotic process; necroptotic process; pyroptotic process; ferroptotic process) (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 13-14). - Inflammatory response / innate immune signaling (cytokine-mediated signaling, inflammasome activation; leukocyte adhesion and endothelial activation in sepsis-associated settings) (aguilar2024sepsisassociatedacutekidney pages 2-4, li2024renaltubularepithelial pages 13-14). - Response to oxidative stress and lipid peroxidation (central to ferroptosis; ROS-linked injury) (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 1-2). - Mitochondrial organization / quality control and metabolic process regulation (mitochondrial dysfunction and metabolic reprogramming are emphasized as AKI-to-AKD mechanisms) (kung2023acutekidneydisease pages 1-3, li2024renaltubularepithelial pages 16-16). - Cell cycle arrest / DNA damage response (a key maladaptive repair mechanism in AKD framing) (kung2023acutekidneydisease pages 1-3). - Extracellular matrix organization / fibrogenesis (pericyte-to-myofibroblast transition; epigenetic maintenance of profibrotic state) (kung2023acutekidneydisease pages 3-4).

5) Cellular components (where key processes occur)

  • Mitochondria: central to TEC vulnerability, ROS generation, apoptosis initiation, and quality-control pathways (li2024renaltubularepithelial pages 1-2, li2024renaltubularepithelial pages 16-16).
  • Plasma membrane: decisive in necroptosis/pyroptosis (rupture or pore formation) and ferroptosis (phospholipid peroxidation-driven membrane failure) (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 1-2).
  • Cytosol: inflammasome assembly (NLRP3 axis) and necroptotic signaling complexes (li2024renaltubularepithelial pages 13-14).
  • Microvascular luminal surface / endothelial glycocalyx: key site of sepsis-associated microcirculatory dysfunction and permeability changes (aguilar2024sepsisassociatedacutekidney pages 2-4).

6) Disease progression (sequence of events; stages/phases)

6.1 Trigger → early injury phase

Common inpatient triggers include infection/sepsis, hemodynamic instability, mechanical ventilation-related physiology, chloride/fluid perturbations, and nephrotoxic drug exposure (havaldar2024epidemiologicalstudyof pages 1-2, mekonnen2024hospitalacquiredacutekidney pages 6-8).

In sepsis-associated contexts, a key modern concept is that injury can occur despite preserved renal blood flow, via microcirculatory/endothelial dysfunction causing regional hypoxia plus inflammatory/oxidative injury (aguilar2024sepsisassociatedacutekidney pages 2-4).

6.2 Injury amplification and clinical syndrome

Tubular cell injury engages regulated cell-death programs (ferroptosis, necroptosis, pyroptosis, apoptosis/PANoptosis), propagating necroinflammation and functional GFR decline (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 1-2).

6.3 Recovery vs maladaptive repair (AKI → AKD window)

If repair is incomplete, the 7–90-day period termed acute kidney disease (AKD) provides a mechanistic bridge to CKD, with drivers including cell-cycle arrest, epigenetic reprogramming, chronic inflammation, mitochondrial dysfunction, failed regeneration, and RAS activation (kung2023acutekidneydisease pages 1-3, kung2023acutekidneydisease pages 3-4).

6.4 Timing distinctions (clinically important in HA-AKI)

In hospitalized cohorts, AKI that peaks later during admission (“in-hospital AKI”) is associated with worse outcomes than AKI present at admission. In one large cohort, in-hospital AKI had longer LOS (mean 26.6 vs 18.7 days) and higher in-hospital mortality (30.7% vs 13.8%) compared with admission AKI (esposito2024recognitionpatternsof pages 7-8).

In septic AKI, later-developing AKI is also linked to higher mortality than early/transient AKI; a 2024 review states: “the development of AKI later during an episode of sepsis has been associated with worse clinical outcomes and increased mortality rates (76.5% compared with 61.5% in early AKI)” (https://doi.org/10.7759/cureus.75992; Dec 2024) (aguilar2024sepsisassociatedacutekidney pages 10-11).

7) Phenotypic manifestations (HP-oriented)

Mechanistically, HA-AKI manifests clinically as acute reductions in filtration and tubular function, often captured by: - Rising serum creatinine / azotemia (used for epidemiologic ascertainment in multiple studies) (esposito2024recognitionpatternsof pages 4-6, havaldar2024epidemiologicalstudyof pages 1-2). - Need for kidney replacement therapy (KRT/RRT) in severe cases; ICU HA-AKI cohort reported 15.9% required RRT during hospitalization (havaldar2024epidemiologicalstudyof pages 1-2). - In-hospital mortality and prolonged stay. ICU HA-AKI cohort mortality was 43.18% vs 14.41% without AKI (havaldar2024epidemiologicalstudyof pages 1-2).

8) Recent developments (2023–2024 emphasis): statistics, biomarkers, and implementation science

8.1 Epidemiology and outcomes in hospital settings (recent data)

  • ICU prospective cohort (2018–2023 enrollment window; published Nov 2024): HA-AKI incidence 16.11% among ICU patients without AKI on admission; hospital mortality 43.18% with HA-AKI; 15.90% required RRT (https://doi.org/10.1038/s41598-024-79533-6) (havaldar2024epidemiologicalstudyof pages 1-2).
  • Large hospitalized cohort (published Jul 2024): overall AKI incidence 24.5%; ICU incidence 59%; ~68% of creatinine-defined AKI was not coded/documented (“KDIGO-AKI”) (https://doi.org/10.1093/ckj/sfae231) (esposito2024recognitionpatternsof pages 4-6, esposito2024recognitionpatternsof pages 1-2).
  • Non-critical medical cohort (published Apr 2024): HA-AKI incidence density 6.0 per 100 person-days; predictors included T2DM and vancomycin/PPI exposure (https://doi.org/10.2147/IJNRD.S454987) (mekonnen2024hospitalacquiredacutekidney pages 1-2).

8.2 Biomarkers and risk stratification (real-world relevance)

Biomarkers are increasingly used to move from “late functional change” (creatinine/urine output) toward earlier “stress/injury” signals.

  • [TIMP-2]·[IGFBP7] + furosemide stress test (FST) to enrich for early RRT need in sepsis-AKI (prospective multicenter; published Jul 2024). In 100 sepsis patients with AKI stage ≥2, 32% required RRT within 7 days. A two-step workflow (FST screen → [TIMP-2]·[IGFBP7] at 2 h) improved prediction accuracy to 0.83 with specificity 0.96 and PPV 0.86 (https://doi.org/10.1186/s13613-024-01349-4) (palmowski2024predictiveenrichmentfor pages 1-2).

  • CCL14 vs [TIMP-2]·[IGFBP7] for predicting renal non-recovery in sepsis-AKI (prospective observational; published May 2024): For 7-day non-recovery prediction, CCL14 AUC 0.901 vs [TIMP-2]·[IGFBP7] AUC 0.730, with reported cutoffs and operating characteristics (https://doi.org/10.1186/s12882-024-03589-9) (nephrology2024predictiveperformanceof pages 7-8).

8.3 Hospital implementation: electronic alerts and care bundles

Electronic AKI alerting systems and linked order sets are widely implemented but show heterogeneous outcome effects.

  • Order set / care-bundle use with alerting (single-center cohort; published Feb 2024): An EHR-integrated AKI order set was used in 9.8% of AKI events and was associated with lower all-cause mortality (multivariable OR 0.72, 95% CI 0.57–0.91) and increased likelihood of AKI-stage improvement (multivariable OR 4.27, 95% CI 3.54–5.14), though LOS was longer when used (https://doi.org/10.1080/0886022X.2024.2313177) (chenxu2024impactofelectronic pages 1-2).

  • RCT-only evidence for alerts (meta-analysis; published Sep 2024): Across six RCTs (n=40,146), e-alerts showed no mortality benefit (RR 1.02), no reduction in creatinine or AKI progression, but increased dialysis (RR 1.14) and increased documentation (RR 1.21) (https://doi.org/10.1186/s12916-024-03639-x) (fu2024effectofelectronic pages 1-2).

  • Broader mixed-design synthesis (systematic review/meta-analysis; 2024): pooled estimates suggested modest AKI progression reduction (RR 0.91) but unclear mortality benefit and increased dialysis (RR 1.16) (chen2024electronicalertsystems pages 6-7).

Interpretation: The collective evidence supports the view that alerts improve recognition/documentation, but clinical outcome improvements require coupling alerts with actionable responses (order sets, care bundles, nephrology/pharmacy workflows) (chenxu2024impactofelectronic pages 1-2, fu2024effectofelectronic pages 1-2).

9) Expert opinions and analysis (from authoritative sources in retrieved set)

9.1 Sepsis-AKI microcirculation paradigm

A key expert framing from a 2024 review is that sepsis-AKI is not simply “low renal blood flow,” but a syndrome in which endothelial activation and microcirculatory dysfunction can create patchy ischemia/hypoxia even when global renal flow is preserved (aguilar2024sepsisassociatedacutekidney pages 2-4).

9.2 AKI as a continuum into AKD/CKD (window for intervention)

A 2023 synthesis emphasizes AKD (7–90 days) as a clinically important period where persistent tubular injury, cell-cycle arrest, epigenetic changes, and metabolic dysfunction can drive progression to CKD, motivating structured follow-up and recurrence prevention (kung2023acutekidneydisease pages 1-3).

10) Knowledge-base ready annotation blocks

10.1 Pathophysiology description (narrative)

Hospital-acquired AKI results from convergent inpatient insults (sepsis/inflammation, microvascular dysfunction, nephrotoxins, ventilation/hemodynamic perturbations) that converge on renal tubular epithelial stress. TEC injury triggers regulated death programs (ferroptosis, necroptosis, pyroptosis, apoptosis/PANoptosis) and mitochondrial/metabolic dysfunction, amplifying inflammation and impairing epithelial repair. Microcirculatory endothelial activation and glycocalyx injury (especially in sepsis) create regional hypoxia and immune-thrombotic injury. Outcomes depend on whether repair is adaptive (successful redifferentiation and recovery) or maladaptive (cell-cycle arrest, persistent inflammation, epigenetic profibrotic programs and pericyte-to-myofibroblast transition), promoting AKD and long-term CKD risk (li2024renaltubularepithelial pages 2-3, aguilar2024sepsisassociatedacutekidney pages 2-4, kung2023acutekidneydisease pages 3-4, li2024renaltubularepithelial media 407547cb).

10.2 Candidate gene/protein annotations (examples)

  • HAVCR1 (KIM-1): tubular injury marker and phagocytic receptor context in TEC apoptosis/injury response (li2024renaltubularepithelial pages 2-3).
  • GPX4: ferroptosis suppressor implicated in TEC ferroptosis biology (li2024renaltubularepithelial pages 13-14, li2024renaltubularepithelial pages 16-16).
  • RIPK1/RIPK3/MLKL: necroptosis machinery linked to inflammatory tubular damage (li2024renaltubularepithelial pages 13-14).
  • NLRP3: inflammasome node linking stress signals to inflammatory injury programs (li2024renaltubularepithelial pages 13-14, li2024renaltubularepithelial pages 16-16).

10.3 Cell type involvement (examples)

  • Tubular epithelial cell (proximal tubule emphasized) (li2024renaltubularepithelial pages 1-2).
  • Endothelial cell / microvascular unit in sepsis-AKI (aguilar2024sepsisassociatedacutekidney pages 2-4).
  • Macrophage (dual roles across injury/repair stages) (li2024renaltubularepithelial pages 11-12).

10.4 Anatomical locations (examples)

  • Renal tubules (proximal tubule segments; tubular cast formation noted in TEC-injury context) (li2024renaltubularepithelial pages 1-2).
  • Renal microcirculation (endothelial activation and shunting in sepsis) (aguilar2024sepsisassociatedacutekidney pages 2-4).
  • Renal interstitium (inflammation/fibrosis in maladaptive repair) (kung2023acutekidneydisease pages 3-4).

10.5 Chemical entities (examples)

  • Vancomycin and PPIs as HA-AKI risk exposures in non-critical inpatients and DI-AKI cohorts (mekonnen2024hospitalacquiredacutekidney pages 6-8, garcia2024druginducedacutekidney pages 3-5).
  • Colistin as an ICU HA-AKI risk factor (havaldar2024epidemiologicalstudyof pages 1-2).

11) Evidence tables and figures

Mechanistic Domain Key Pathways/Processes Key Genes/Proteins (HGNC) Primary Cell Types (CL) Anatomical Locations (UBERON) Representative Chemicals (CHEBI) Evidence
Regulated Cell Death: Ferroptosis Lipid peroxidation; System Xc- inhibition; Iron metabolism dysregulation; Membrane rupture GPX4, SLC7A11, ACSL4 Kidney tubular epithelial cell (CL:0000653) Proximal convoluted tubule (UBERON:0004134) Iron (CHEBI:18248), Glutathione (CHEBI:16856), Lipid peroxides Li et al. 2024 (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 1-2, li2024renaltubularepithelial pages 11-12)
Regulated Cell Death: Necroptosis RIPK1-RIPK3 signaling; MLKL phosphorylation/oligomerization; "Necroinflammation" RIPK1, RIPK3, MLKL Kidney tubular epithelial cell (CL:0000653) Renal tubule (UBERON:0001231) TNF-alpha (CHEBI:132922) Li et al. 2024 (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 13-14)
Inflammation & Pyroptosis NLRP3 inflammasome activation; STING-mtROS axis; Gasdermin pore formation; Cytokine release NLRP3, GSDMD, CASP1, TMEM173 (STING) Kidney tubular epithelial cell; Macrophage (CL:0000235) Renal interstitium (UBERON:0001233) IL-1beta, IL-18, Lipopolysaccharide (CHEBI:16412) Li et al. 2024 (li2024renaltubularepithelial pages 13-14, li2024renaltubularepithelial pages 16-16)
Mitochondrial & Metabolic Reprogramming Defective Fatty Acid Oxidation (FAO); Shift to Glycolysis; Mitochondrial fission/fusion; Mitophagy failure CPT1A, PPARA, PKM, PINK1, PRKN Proximal straight tubule epithelial cell (CL:0002306) Mitochondrion (GO:0005739) in Kidney (UBERON:0002113) Fatty acids (CHEBI:35366), Lactate (CHEBI:24996), ATP (CHEBI:15422) Cao et al. 2025 (cao2025mitochondrialdysfunctionand pages 4-6); Li et al. 2024 (li2024renaltubularepithelial pages 16-16)
Microvascular & Endothelial Dysfunction Glycocalyx degradation; Endothelial activation; Leukocyte adhesion; Microthrombosis; Capillary shunting VCAM1, ICAM1, SELE (Selectins) Endothelial cell (CL:0000115) Glomerular capillary (UBERON:0004642); Peritubular capillary Nitric oxide (CHEBI:16480), VEGF Aguilar et al. 2024 (aguilar2024sepsisassociatedacutekidney pages 2-4, aguilar2024sepsisassociatedacutekidney pages 10-11)
Nephrotoxicity (Drug-Induced) Acute Tubular Necrosis (ATN); Acute Interstitial Nephritis (AIN); Intratubular crystal deposition; Oxidative stress SLC22A6 (OAT1 - implied), LRP2 (Megalin - implied) Kidney tubular epithelial cell Renal tubule; Renal interstitium Vancomycin (CHEBI:9948), Cisplatin (CHEBI:27899), Contrast media Garcia et al. 2024 (garcia2024druginducedacutekidney pages 1-2, garcia2024druginducedacutekidney pages 2-3, garcia2024druginducedacutekidney pages 6-8)
Maladaptive Repair & Fibrosis G2/M cell cycle arrest; Pericyte-to-myofibroblast transition; Epigenetic hypermethylation TGFB1, RASAL1, ACTA2 (alpha-SMA) Kidney pericyte (CL:0000669); Myofibroblast Renal interstitium 5-azacytidine (CHEBI:2704 - experimental reversal) Kung et al. 2023 (kung2023acutekidneydisease pages 3-4)

Table: This table summarizes the core pathophysiological domains of HA-AKI, detailing key pathways, molecular players, affected cell types, and anatomical sites, along with associated chemical entities and supporting evidence from recent literature.

A schematic figure summarizing adaptive vs maladaptive TEC repair trajectories (Figure 1, Li et al. 2024) is available (li2024renaltubularepithelial media 407547cb).

12) Limitations of the evidence base retrieved here

  • PMIDs were not present in the full-text excerpts retrieved for most 2023–2024 papers, so citations here use DOI + publication month/year from the papers themselves (aguilar2024sepsisassociatedacutekidney pages 2-4, li2024renaltubularepithelial pages 1-2, havaldar2024epidemiologicalstudyof pages 1-2). A PubMed lookup step would be required to attach PMIDs systematically.
  • Some mechanistic themes (e.g., STING/ER stress axis) are represented in the retrieved corpus primarily through sepsis-focused materials rather than HA-AKI-specific cohorts; nevertheless, sepsis is a major HA-AKI etiology in hospital settings (havaldar2024epidemiologicalstudyof pages 1-2, aguilar2024sepsisassociatedacutekidney pages 2-4).

Key source URLs (most used, 2023–2024)

  • Esposito et al., Clinical Kidney Journal (Jul 2024): https://doi.org/10.1093/ckj/sfae231 (esposito2024recognitionpatternsof pages 1-2, esposito2024recognitionpatternsof pages 4-6)
  • Havaldar et al., Scientific Reports (Nov 2024): https://doi.org/10.1038/s41598-024-79533-6 (havaldar2024epidemiologicalstudyof pages 1-2)
  • Li et al., eBioMedicine (Sep 2024): https://doi.org/10.1016/j.ebiom.2024.105294 (li2024renaltubularepithelial pages 1-2, li2024renaltubularepithelial media 407547cb)
  • Palmowski et al., Annals of Intensive Care (Jul 2024): https://doi.org/10.1186/s13613-024-01349-4 (palmowski2024predictiveenrichmentfor pages 1-2)
  • Fu et al., BMC Medicine (Sep 2024): https://doi.org/10.1186/s12916-024-03639-x (fu2024effectofelectronic pages 1-2)
  • Garcia et al., Frontiers in Medicine (Oct 2024): https://doi.org/10.3389/fmed.2024.1459170 (garcia2024druginducedacutekidney pages 3-5)
  • Mekonnen et al., IJNRD (Apr 2024): https://doi.org/10.2147/IJNRD.S454987 (mekonnen2024hospitalacquiredacutekidney pages 1-2)
  • Kung & Chou, Kidney Research and Clinical Practice (Nov 2023): https://doi.org/10.23876/j.krcp.23.001 (kung2023acutekidneydisease pages 1-3)

References

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