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Polycystic Kidney Disease

Mendelian MONDO:0020642 Genetic Kidney Disease Ciliopathy

Polycystic kidney disease (PKD) is a genetic disorder characterized by the development of multiple fluid-filled cysts in the kidneys. The autosomal dominant form (ADPKD) is one of the most common inherited kidney diseases, affecting approximately 1 in 500-1000 people. ADPKD is caused by mutations in PKD1 or PKD2 genes and typically presents in adulthood with progressive renal enlargement, hypertension, and eventual kidney failure. Autosomal recessive PKD (ARPKD) is less common and typically presents in infancy or childhood.

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Mappings
0
Definitions
0
Inheritance
4
Pathophysiology
0
Histopathology
6
Phenotypes
3
Genes
4
Treatments
2
Subtypes
3
Differentials
2
Datasets
0
Trials
◆

Subtypes

2
Autosomal Dominant PKD (ADPKD)
Most common form, caused by PKD1 or PKD2 mutations, typically presenting in adulthood.
Autosomal Recessive PKD (ARPKD)
Less common form caused by PKHD1 mutations, presenting in infancy or childhood with more severe phenotype.
⚙

Pathophysiology

4
Vasopressin/cAMP-Driven Cyst Expansion
Elevated vasopressin signaling via V2 receptors increases cAMP in tubular epithelial cells, driving chloride and fluid secretion into cysts and promoting cyst wall growth. Blocking V2 signaling slows total kidney volume expansion.
nephron tubule epithelial cell link
cAMP/PKA signal transduction link
Show evidence (1 reference)
PMID:29105594 SUPPORT
"the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume"
Tolvaptan’s effect on kidney volume underscores vasopressin/cAMP signaling as a key driver of cyst expansion.
Epithelial Proliferation and Kidney Enlargement
Reduced polycystin-mediated restraint on epithelial proliferation leads to progressive cyst wall growth and parenchymal compression, increasing total kidney volume and reducing renal function.
nephron tubule epithelial cell link
regulation of cell proliferation link
Show evidence (1 reference)
PMID:29105594 SUPPORT
"slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate"
Dampening kidney volume growth parallels slower GFR loss, linking cyst epithelial proliferation to functional decline.
Ciliary Dysfunction
Primary cilia act as mechanosensors in renal tubular epithelial cells. Polycystin dysfunction impairs ciliary signaling, disrupting normal tubular architecture and promoting cyst formation through increased cAMP signaling.
nephron tubule epithelial cell link
cilium organization link cAMP/PKA signal transduction link
Show evidence (1 reference)
PMID:29105594 SUPPORT
"the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume"
Reduction of cyst growth via V2 receptor blockade underscores cAMP-mediated ciliary signaling as a driver of cystogenesis.
Fibrosis and Inflammation
Progressive cyst growth triggers interstitial inflammation and fibrosis. Activated myofibroblasts deposit extracellular matrix, contributing to nephron loss and declining kidney function.
macrophage link
inflammatory response link
Show evidence (1 reference)
PMID:40126492 SUPPORT
"ADPKD accounts for 5% to 10% of kidney failure in the US and Europe"
High kidney failure burden reflects cumulative nephron loss from cyst-driven injury and interstitial fibrosis.
●

Phenotypes

6
Cardiovascular(2) Digestive(1) Genitourinary(2) Constitutional(1)
Cardiovascular 2
Hypertension VERY_FREQUENT Hypertension (HP:0000822)
Show evidence (3 references)
PMID:40126492 SUPPORT
"Hypertension affects 70% to 80% of patients with ADPKD"
JAMA review confirms very high prevalence of hypertension in ADPKD patients.
PMID:40126492 SUPPORT
"Optimal management of ADPKD includes systolic blood pressure lower than 120 mm Hg for most patients"
Tight blood pressure targets underscore hypertension as a central clinical issue in ADPKD.
PMID:40371605 SUPPORT
"Comorbidities include hypertension, flank pain, and bacterial infections."
Proteomic study lists hypertension as a common comorbidity in ADPKD cohorts.
Intracranial Aneurysm OCCASIONAL Cerebral berry aneurysm (HP:0007029)
Show evidence (1 reference)
PMID:40126492 SUPPORT
"approximately 9% to 14% develop intracranial aneurysms"
JAMA review confirms intracranial aneurysms occur in 9-14% of ADPKD patients.
Digestive 1
Hepatic Cysts FREQUENT Hepatic cysts (HP:0001407)
Show evidence (2 references)
PMID:40126492 SUPPORT
"More than 90% of patients older than 35 years have hepatic cysts"
JAMA review confirms hepatic cysts as a very common manifestation in ADPKD.
PMID:40126492 SUPPORT
"More than 90% of patients older than 35 years have hepatic cysts, which may cause abdominal discomfort and occasionally require medical or surgical intervention"
Describes prevalence plus symptomatic burden and intervention needs from hepatic cysts in ADPKD.
Genitourinary 2
Multiple Renal Cysts VERY_FREQUENT Multiple renal cysts (HP:0005562)
Show evidence (2 references)
PMID:29105594 SUPPORT
"the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume"
REPRISE trial confirms PKD as a cystic kidney disease defined by progressive kidney volume increase.
PMID:40126492 SUPPORT
"Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of kidney cysts"
JAMA review describes ADPKD as a progressive cystic kidney disease.
Chronic Kidney Disease VERY_FREQUENT Chronic kidney disease (HP:0012622)
Show evidence (2 references)
PMID:29105594 SUPPORT
"The change from baseline in the estimated GFR was -2.34 ml per minute per 1.73 m2"
Trial demonstrates progressive GFR decline in PKD patients.
PMID:40126492 SUPPORT
"Approximately 50% of individuals with ADPKD require kidney replacement therapy by 62 years of age"
High rate of kidney replacement therapy highlights progression to advanced CKD in ADPKD.
Constitutional 1
Flank Pain FREQUENT Flank pain (HP:0030157)
Show evidence (1 reference)
PMID:40371605 SUPPORT
"Comorbidities include hypertension, flank pain, and bacterial infections."
Proteomic study notes flank pain as a common comorbidity in ADPKD patients.
🧬

Genetic Associations

3
PKD1 Mutations (Causative)
Show evidence (1 reference)
PMID:40126492 SUPPORT
"ADPKD is typically diagnosed in individuals aged 27 to 42 years and is primarily caused by pathogenic variants in the PKD1 (78%) or PKD2 (15%) genes."
JAMA review quantifies PKD1 as the predominant cause of ADPKD.
PKD2 Mutations (Causative)
Show evidence (1 reference)
PMID:40126492 SUPPORT
"ADPKD is typically diagnosed in individuals aged 27 to 42 years and is primarily caused by pathogenic variants in the PKD1 (78%) or PKD2 (15%) genes."
JAMA review documents PKD2 as a minority but established cause of ADPKD.
PKHD1 Mutations (Causative)
Show evidence (1 reference)
PMID:41467628 SUPPORT
"Autosomal recessive polycystic kidney disease (ARPKD) is a rare disorder mainly caused by mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene."
Clin Nephrol study states PKHD1 mutations as the primary cause of ARPKD.
💊

Treatments

4
Tolvaptan MAXO:0000058
Drug: tolvaptan ↗
Vasopressin V2 receptor antagonist that slows cyst growth and kidney enlargement in ADPKD. First disease-modifying therapy approved for ADPKD. Requires hepatic monitoring due to risk of elevated liver enzymes.
Show evidence (1 reference)
PMID:29105594 SUPPORT
"Tolvaptan resulted in a slower decline than placebo in the estimated GFR over a 1-year period in patients with later-stage ADPKD."
REPRISE trial demonstrated tolvaptan efficacy in slowing GFR decline in PKD patients.
Blood Pressure Control MAXO:0000058
Aggressive hypertension management with ACE inhibitors or ARBs to slow disease progression and reduce cardiovascular risk.
Show evidence (1 reference)
PMID:40126492 SUPPORT
"First-line treatment includes blood pressure control, dietary and weight management, and adequate hydration."
JAMA review confirms blood pressure control as first-line treatment for ADPKD.
Renal Dialysis MAXO:0000601
Dialysis (hemodialysis or peritoneal dialysis) for end-stage renal disease. PKD is one of the leading causes of kidney failure requiring dialysis.
Show evidence (1 reference)
PMID:40126492 SUPPORT
"Approximately 50% of individuals with ADPKD require kidney replacement therapy by 62 years of age."
JAMA review confirms high rate of kidney replacement therapy (dialysis/transplant) in ADPKD.
Kidney Transplantation MAXO:0010039
Kidney transplantation is the preferred treatment for end-stage renal disease in PKD. Native nephrectomy may be required if kidneys are too large.
Show evidence (1 reference)
PMID:40126492 SUPPORT
"Approximately 50% of individuals with ADPKD require kidney replacement therapy by 62 years of age."
JAMA review confirms high rate of kidney replacement therapy (dialysis/transplant) in ADPKD.
🌍

Environmental Factors

1
Caffeine Consumption
May accelerate cyst growth through increased cAMP levels; patients often advised to limit intake
Show evidence (1 reference)
PMID:20301424 SUPPORT
"Agents/circumstances to avoid: ... high levels of caffeine"
GeneReviews lists high caffeine intake as an avoidable factor in ADPKD management.
🔬

Biochemical Markers

2
Elevated Creatinine (Elevated)
Context: Marker of declining renal function in advanced disease
Show evidence (1 reference)
PMID:29105594 SUPPORT
"The change from baseline in the estimated GFR was -2.34 ml per minute per 1.73 m2"
Progressive GFR decline reflects rising creatinine as renal function deteriorates.
Decreased GFR (Decreased)
Context: Progressive decline reflecting nephron loss
Show evidence (1 reference)
PMID:29105594 SUPPORT
"as compared with -3.61 ml per minute per 1.73 m2 (95% CI, -4.08 to -3.14) in the placebo group"
Trial quantifies ongoing GFR loss in ADPKD absent disease-modifying therapy.
🔀

Differential Diagnoses

3

Conditions with similar clinical presentations that must be differentiated from Polycystic Kidney Disease:

Simple Renal Cysts (Age-Related) Not Yet Curated MONDO:0004840
Overlapping Features Solitary or few benign cysts that enlarge slowly with age and lack family history or extrarenal cysts. ADPKD shows bilateral numerous cysts with progressive total kidney volume growth.
Distinguishing Features
  • Typically solitary or few cysts without kidney enlargement
  • No hepatic cysts or family history of cystic disease
  • Stable kidney function and volume over time
Show evidence (1 reference)
PMID:29105594 SUPPORT
"the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume"
Progressive total kidney volume growth distinguishes ADPKD from stable simple cysts.
Acquired Cystic Kidney Disease (ACKD) Not Yet Curated MONDO:0002473
Overlapping Features Cystic change that develops in chronically dialyzed kidneys, usually in the setting of long-standing kidney failure. Kidneys are often small or normal size rather than massively enlarged as in ADPKD.
Distinguishing Features
  • Occurs after years of dialysis or advanced CKD without family history
  • Kidneys remain small/normal sized rather than enlarged
  • Lacks extensive hepatic cysts common in ADPKD
Show evidence (1 reference)
PMID:40126492 SUPPORT
"Patients with MIC 1C to MIC 1E have larger kidneys because of more rapid growth (6%-10% per year)"
Rapid kidney enlargement in ADPKD contrasts with small kidneys seen in ACKD.
Tuberous Sclerosis Complex (TSC) Not Yet Curated MONDO:0001734
Overlapping Features Genetic disorder with renal cysts and angiomyolipomas that can mimic ADPKD but accompanied by dermatologic and neurologic manifestations.
Distinguishing Features
  • Renal angiomyolipomas and cortical tubers with seizures or developmental issues
  • Cutaneous findings (facial angiofibromas, hypomelanotic macules) absent in ADPKD
  • ADPKD frequently shows extensive hepatic cysts, which are uncommon in TSC
Show evidence (1 reference)
PMID:40126492 SUPPORT
"More than 90% of patients older than 35 years have hepatic cysts"
High hepatic cyst burden supports ADPKD over TSC when liver cysts dominate.
📊

Related Datasets

2
Expression data from renal cysts of autosomal dominant polycystic kidney disease (ADPKD) patients geo:GSE7869
Microarray profiling comparing ADPKD kidney cyst epithelium with non-cystic kidney tissue to identify dysregulated pathways in cyst growth.
human MICROARRAY
kidney epithelium
Conditions: ADPKD cyst epithelium non-cystic kidney tissue
PMID:19346236
Public ADPKD microarray dataset frequently used to study cystogenesis-related signaling changes.
Show evidence (2 references)
PMID:23524344 SUPPORT
"Microarray data are available at GEO website (accession number: GSE7869)."
Confirms the GEO accession for the ADPKD cyst epithelium microarray dataset.
PMID:19346236 SUPPORT
"To elucidate the molecular pathways that modulate renal cyst growth in ADPKD, we performed global gene profiling on cysts of different size (<1 ml, n = 5; 10-20 ml, n = 5; >50 ml, n = 3) and minimally cystic tissue (MCT, n = 5) from five PKD1 human polycystic kidneys using Affymetrix HG-U133..."
Describes the PKD1 cyst epithelium microarray experiment underlying GSE7869.
GTEx v8 kidney cortex bulk RNA-seq gtex:GTEx_v8_Kidney_Cortex
Bulk RNA-seq from healthy kidney cortex samples providing control transcriptomes for comparison to ADPKD cystic tissue.
human BULK RNA SEQ
kidney cortex
PMID:39815096
Healthy kidney reference transcriptomes useful as baseline controls for differential expression analyses in ADPKD studies.
Show evidence (1 reference)
PMID:39815096 SUPPORT
"The data will comprise whole-genome sequencing, extensive bulk, single-cell and spatial gene expression profiles, and chromatin accessibility data across tissues and development."
Establishes dGTEx as a bulk expression resource providing control transcriptomes across tissues including kidney.
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Source YAML

click to show 
name: Polycystic Kidney Disease
creation_date: '2026-01-09T06:06:08Z'
updated_date: '2026-02-27T21:53:02Z'
category: Mendelian
description: >
  Polycystic kidney disease (PKD) is a genetic disorder characterized by the
  development of multiple fluid-filled cysts in the kidneys. The autosomal dominant
  form (ADPKD) is one of the most common inherited kidney diseases, affecting
  approximately 1 in 500-1000 people. ADPKD is caused by mutations in PKD1 or PKD2
  genes and typically presents in adulthood with progressive renal enlargement,
  hypertension, and eventual kidney failure. Autosomal recessive PKD (ARPKD) is
  less common and typically presents in infancy or childhood.
disease_term:
  preferred_term: polycystic kidney disease
  term:
    id: MONDO:0020642
    label: polycystic kidney disease
parents:
- Genetic Kidney Disease
- Ciliopathy
has_subtypes:
- name: Autosomal Dominant PKD (ADPKD)
  description: Most common form, caused by PKD1 or PKD2 mutations, typically presenting in adulthood.
- name: Autosomal Recessive PKD (ARPKD)
  description: Less common form caused by PKHD1 mutations, presenting in infancy or childhood with more severe phenotype.
pathophysiology:
- name: Vasopressin/cAMP-Driven Cyst Expansion
  description: >
    Elevated vasopressin signaling via V2 receptors increases cAMP in tubular
    epithelial cells, driving chloride and fluid secretion into cysts and promoting
    cyst wall growth. Blocking V2 signaling slows total kidney volume expansion.
  evidence:
  - reference: PMID:29105594
    supports: SUPPORT
    snippet: "the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume"
    explanation: Tolvaptan’s effect on kidney volume underscores vasopressin/cAMP signaling as a key driver of cyst expansion.
  cell_types:
  - preferred_term: nephron tubule epithelial cell
    term:
      id: CL:1000494
      label: nephron tubule epithelial cell
  biological_processes:
  - preferred_term: cAMP/PKA signal transduction
    term:
      id: GO:0141156
      label: cAMP/PKA signal transduction
- name: Epithelial Proliferation and Kidney Enlargement
  description: >
    Reduced polycystin-mediated restraint on epithelial proliferation leads to
    progressive cyst wall growth and parenchymal compression, increasing total
    kidney volume and reducing renal function.
  evidence:
  - reference: PMID:29105594
    supports: SUPPORT
    snippet: "slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate"
    explanation: Dampening kidney volume growth parallels slower GFR loss, linking cyst epithelial proliferation to functional decline.
  cell_types:
  - preferred_term: nephron tubule epithelial cell
    term:
      id: CL:1000494
      label: nephron tubule epithelial cell
  biological_processes:
  - preferred_term: regulation of cell proliferation
    term:
      id: GO:0042127
      label: regulation of cell proliferation
- name: Ciliary Dysfunction
  description: >
    Primary cilia act as mechanosensors in renal tubular epithelial cells.
    Polycystin dysfunction impairs ciliary signaling, disrupting normal tubular
    architecture and promoting cyst formation through increased cAMP signaling.
  evidence:
  - reference: PMID:29105594
    supports: SUPPORT
    snippet: "the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume"
    explanation: Reduction of cyst growth via V2 receptor blockade underscores cAMP-mediated ciliary signaling as a driver of cystogenesis.
  cell_types:
  - preferred_term: nephron tubule epithelial cell
    term:
      id: CL:1000494
      label: nephron tubule epithelial cell
  biological_processes:
  - preferred_term: cilium organization
    term:
      id: GO:0044782
      label: cilium organization
  - preferred_term: cAMP/PKA signal transduction
    term:
      id: GO:0141156
      label: cAMP/PKA signal transduction
- name: Fibrosis and Inflammation
  description: >
    Progressive cyst growth triggers interstitial inflammation and fibrosis.
    Activated myofibroblasts deposit extracellular matrix, contributing to
    nephron loss and declining kidney function.
  evidence:
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "ADPKD accounts for 5% to 10% of kidney failure in the US and Europe"
    explanation: High kidney failure burden reflects cumulative nephron loss from cyst-driven injury and interstitial fibrosis.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
phenotypes:
- name: Multiple Renal Cysts
  category: Renal
  frequency: VERY_FREQUENT
  description: Multiple fluid-filled cysts in both kidneys, progressively enlarging over time.
  phenotype_term:
    preferred_term: Multiple renal cysts
    term:
      id: HP:0005562
      label: Multiple renal cysts
  evidence:
  - reference: PMID:29105594
    supports: SUPPORT
    snippet: "the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume"
    explanation: REPRISE trial confirms PKD as a cystic kidney disease defined by progressive kidney volume increase.
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of kidney cysts"
    explanation: JAMA review describes ADPKD as a progressive cystic kidney disease.
- name: Hypertension
  category: Cardiovascular
  frequency: VERY_FREQUENT
  description: High blood pressure, often preceding decline in renal function.
  phenotype_term:
    preferred_term: Hypertension
    term:
      id: HP:0000822
      label: Hypertension
  evidence:
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "Hypertension affects 70% to 80% of patients with ADPKD"
    explanation: "JAMA review confirms very high prevalence of hypertension in ADPKD patients."
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "Optimal management of ADPKD includes systolic blood pressure lower than 120 mm Hg for most patients"
    explanation: Tight blood pressure targets underscore hypertension as a central clinical issue in ADPKD.
  - reference: PMID:40371605
    supports: SUPPORT
    snippet: "Comorbidities include hypertension, flank pain, and bacterial infections."
    explanation: Proteomic study lists hypertension as a common comorbidity in ADPKD cohorts.
- name: Chronic Kidney Disease
  category: Renal
  frequency: VERY_FREQUENT
  description: Progressive decline in kidney function, with approximately 50% reaching end-stage renal disease by age 60.
  phenotype_term:
    preferred_term: Chronic kidney disease
    term:
      id: HP:0012622
      label: Chronic kidney disease
  evidence:
  - reference: PMID:29105594
    supports: SUPPORT
    snippet: "The change from baseline in the estimated GFR was -2.34 ml per minute per 1.73 m2"
    explanation: Trial demonstrates progressive GFR decline in PKD patients.
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "Approximately 50% of individuals with ADPKD require kidney replacement therapy by 62 years of age"
    explanation: High rate of kidney replacement therapy highlights progression to advanced CKD in ADPKD.
- name: Hepatic Cysts
  category: Hepatic
  frequency: FREQUENT
  description: Liver cysts are common extrarenal manifestation, more prevalent in women.
  phenotype_term:
    preferred_term: Hepatic cysts
    term:
      id: HP:0001407
      label: Hepatic cysts
  evidence:
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "More than 90% of patients older than 35 years have hepatic cysts"
    explanation: "JAMA review confirms hepatic cysts as a very common manifestation in ADPKD."
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "More than 90% of patients older than 35 years have hepatic cysts, which may cause abdominal discomfort and occasionally require medical or surgical intervention"
    explanation: Describes prevalence plus symptomatic burden and intervention needs from hepatic cysts in ADPKD.
- name: Intracranial Aneurysm
  category: Vascular
  frequency: OCCASIONAL
  description: Cerebral berry aneurysms occur in 5-10% of ADPKD patients, with risk of rupture.
  phenotype_term:
    preferred_term: Cerebral berry aneurysm
    term:
      id: HP:0007029
      label: Cerebral berry aneurysm
  evidence:
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "approximately 9% to 14% develop intracranial aneurysms"
    explanation: "JAMA review confirms intracranial aneurysms occur in 9-14% of ADPKD patients."
- name: Flank Pain
  category: Renal
  frequency: FREQUENT
  description: Chronic or acute pain due to cyst hemorrhage, infection, or mass effect.
  phenotype_term:
    preferred_term: Flank pain
    term:
      id: HP:0030157
      label: Flank pain
  evidence:
  - reference: PMID:40371605
    supports: SUPPORT
    snippet: "Comorbidities include hypertension, flank pain, and bacterial infections."
    explanation: Proteomic study notes flank pain as a common comorbidity in ADPKD patients.
biochemical:
- name: Elevated Creatinine
  presence: Elevated
  context: Marker of declining renal function in advanced disease
  evidence:
  - reference: PMID:29105594
    supports: SUPPORT
    snippet: "The change from baseline in the estimated GFR was -2.34 ml per minute per 1.73 m2"
    explanation: Progressive GFR decline reflects rising creatinine as renal function deteriorates.
- name: Decreased GFR
  presence: Decreased
  context: Progressive decline reflecting nephron loss
  evidence:
  - reference: PMID:29105594
    supports: SUPPORT
    snippet: "as compared with -3.61 ml per minute per 1.73 m2 (95% CI, -4.08 to -3.14) in the placebo group"
    explanation: Trial quantifies ongoing GFR loss in ADPKD absent disease-modifying therapy.
genetic:
- name: PKD1 Mutations
  association: Causative
  notes: Accounts for approximately 85% of ADPKD cases; encodes polycystin-1; typically more severe phenotype with earlier onset of ESRD
  evidence:
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "ADPKD is typically diagnosed in individuals aged 27 to 42 years and is primarily caused by pathogenic variants in the PKD1 (78%) or PKD2 (15%) genes."
    explanation: JAMA review quantifies PKD1 as the predominant cause of ADPKD.
- name: PKD2 Mutations
  association: Causative
  notes: Accounts for approximately 15% of ADPKD cases; encodes polycystin-2; milder phenotype with later onset of ESRD
  evidence:
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "ADPKD is typically diagnosed in individuals aged 27 to 42 years and is primarily caused by pathogenic variants in the PKD1 (78%) or PKD2 (15%) genes."
    explanation: JAMA review documents PKD2 as a minority but established cause of ADPKD.
- name: PKHD1 Mutations
  association: Causative
  notes: Causes autosomal recessive PKD; encodes fibrocystin/polyductin
  evidence:
  - reference: PMID:41467628
    supports: SUPPORT
    snippet: "Autosomal recessive polycystic kidney disease (ARPKD) is a rare disorder mainly caused by mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene."
    explanation: Clin Nephrol study states PKHD1 mutations as the primary cause of ARPKD.
environmental:
- name: Caffeine Consumption
  notes: May accelerate cyst growth through increased cAMP levels; patients often advised to limit intake
  evidence:
  - reference: PMID:20301424
    supports: SUPPORT
    snippet: "Agents/circumstances to avoid: ... high levels of caffeine"
    explanation: GeneReviews lists high caffeine intake as an avoidable factor in ADPKD management.
treatments:
- name: Tolvaptan
  description: >
    Vasopressin V2 receptor antagonist that slows cyst growth and kidney
    enlargement in ADPKD. First disease-modifying therapy approved for ADPKD.
    Requires hepatic monitoring due to risk of elevated liver enzymes.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    therapeutic_agent:
    - preferred_term: tolvaptan
      term:
        id: CHEBI:32246
        label: tolvaptan
  evidence:
  - reference: PMID:29105594
    supports: SUPPORT
    snippet: "Tolvaptan resulted in a slower decline than placebo in the estimated GFR over a 1-year period in patients with later-stage ADPKD."
    explanation: REPRISE trial demonstrated tolvaptan efficacy in slowing GFR decline in PKD patients.
- name: Blood Pressure Control
  description: >
    Aggressive hypertension management with ACE inhibitors or ARBs to slow
    disease progression and reduce cardiovascular risk.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
  evidence:
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "First-line treatment includes blood pressure control, dietary and weight management, and adequate hydration."
    explanation: "JAMA review confirms blood pressure control as first-line treatment for ADPKD."
- name: Renal Dialysis
  description: >
    Dialysis (hemodialysis or peritoneal dialysis) for end-stage renal disease.
    PKD is one of the leading causes of kidney failure requiring dialysis.
  treatment_term:
    preferred_term: renal dialysis
    term:
      id: MAXO:0000601
      label: renal dialysis
  evidence:
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "Approximately 50% of individuals with ADPKD require kidney replacement therapy by 62 years of age."
    explanation: "JAMA review confirms high rate of kidney replacement therapy (dialysis/transplant) in ADPKD."
- name: Kidney Transplantation
  description: >
    Kidney transplantation is the preferred treatment for end-stage renal disease
    in PKD. Native nephrectomy may be required if kidneys are too large.
  treatment_term:
    preferred_term: organ transplantation
    term:
      id: MAXO:0010039
      label: organ transplantation
  evidence:
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "Approximately 50% of individuals with ADPKD require kidney replacement therapy by 62 years of age."
    explanation: "JAMA review confirms high rate of kidney replacement therapy (dialysis/transplant) in ADPKD."
differential_diagnoses:
- name: Simple Renal Cysts (Age-Related)
  disease_term:
    preferred_term: simple renal cyst
    term:
      id: MONDO:0004840
      label: non-congenital cyst of kidney
  description: >
    Solitary or few benign cysts that enlarge slowly with age and lack family history
    or extrarenal cysts. ADPKD shows bilateral numerous cysts with progressive total
    kidney volume growth.
  distinguishing_features:
  - Typically solitary or few cysts without kidney enlargement
  - No hepatic cysts or family history of cystic disease
  - Stable kidney function and volume over time
  evidence:
  - reference: PMID:29105594
    supports: SUPPORT
    snippet: "the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume"
    explanation: Progressive total kidney volume growth distinguishes ADPKD from stable simple cysts.
- name: Acquired Cystic Kidney Disease (ACKD)
  disease_term:
    preferred_term: acquired cystic kidney disease
    term:
      id: MONDO:0002473
      label: cystic kidney disease
  description: >
    Cystic change that develops in chronically dialyzed kidneys, usually in the
    setting of long-standing kidney failure. Kidneys are often small or normal size
    rather than massively enlarged as in ADPKD.
  distinguishing_features:
  - Occurs after years of dialysis or advanced CKD without family history
  - Kidneys remain small/normal sized rather than enlarged
  - Lacks extensive hepatic cysts common in ADPKD
  evidence:
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "Patients with MIC 1C to MIC 1E have larger kidneys because of more rapid growth (6%-10% per year)"
    explanation: Rapid kidney enlargement in ADPKD contrasts with small kidneys seen in ACKD.
- name: Tuberous Sclerosis Complex (TSC)
  disease_term:
    preferred_term: tuberous sclerosis
    term:
      id: MONDO:0001734
      label: tuberous sclerosis
  description: >
    Genetic disorder with renal cysts and angiomyolipomas that can mimic ADPKD but
    accompanied by dermatologic and neurologic manifestations.
  distinguishing_features:
  - Renal angiomyolipomas and cortical tubers with seizures or developmental issues
  - Cutaneous findings (facial angiofibromas, hypomelanotic macules) absent in ADPKD
  - ADPKD frequently shows extensive hepatic cysts, which are uncommon in TSC
  evidence:
  - reference: PMID:40126492
    supports: SUPPORT
    snippet: "More than 90% of patients older than 35 years have hepatic cysts"
    explanation: High hepatic cyst burden supports ADPKD over TSC when liver cysts dominate.
datasets:
- accession: geo:GSE7869
  title: Expression data from renal cysts of autosomal dominant polycystic kidney disease (ADPKD) patients
  description: Microarray profiling comparing ADPKD kidney cyst epithelium with non-cystic kidney tissue to identify dysregulated pathways in cyst growth.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: MICROARRAY
  sample_types:
  - preferred_term: kidney epithelium
    tissue_term:
      preferred_term: kidney
      term:
        id: UBERON:0002113
        label: kidney
  conditions:
  - ADPKD cyst epithelium
  - non-cystic kidney tissue
  publication: PMID:19346236
  notes: >-
    Public ADPKD microarray dataset frequently used to study cystogenesis-related signaling changes.
  evidence:
  - reference: PMID:23524344
    supports: SUPPORT
    snippet: "Microarray data are available at GEO website (accession number: GSE7869)."
    explanation: Confirms the GEO accession for the ADPKD cyst epithelium microarray dataset.
  - reference: PMID:19346236
    supports: SUPPORT
    snippet: "To elucidate the molecular pathways that modulate renal cyst growth in ADPKD, we performed global gene profiling on cysts of different size (<1 ml, n = 5; 10-20 ml, n = 5; >50 ml, n = 3) and minimally cystic tissue (MCT, n = 5) from five PKD1 human polycystic kidneys using Affymetrix HG-U133 Plus 2.0 arrays."
    explanation: Describes the PKD1 cyst epithelium microarray experiment underlying GSE7869.

- accession: gtex:GTEx_v8_Kidney_Cortex
  title: GTEx v8 kidney cortex bulk RNA-seq
  description: Bulk RNA-seq from healthy kidney cortex samples providing control transcriptomes for comparison to ADPKD cystic tissue.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_types:
  - preferred_term: kidney cortex
    tissue_term:
      preferred_term: kidney cortex
      term:
        id: UBERON:0001225
        label: kidney cortex
  publication: PMID:39815096
  notes: >-
    Healthy kidney reference transcriptomes useful as baseline controls for differential expression analyses in ADPKD studies.
  evidence:
  - reference: PMID:39815096
    supports: SUPPORT
    snippet: "The data will comprise whole-genome sequencing, extensive bulk, single-cell and spatial gene expression profiles, and chromatin accessibility data across tissues and development."
    explanation: Establishes dGTEx as a bulk expression resource providing control transcriptomes across tissues including kidney.