Polycystic kidney disease (PKD)

Polycystic kidney disease (PKD) is generally defined by bilateral renal cyst formation, progressive nephromegaly, and variable extrarenal manifestations. Based on their patterns of inheritance, the various disease entities can be broadly categorised into autosomal dominant (ADPKD) and autosomal recessive (ARPKD) polycystic kidney disease. ADPKD typically presents in adulthood with hypertension, microscopic or macroscopic hematuria, recurrent urinary tract infections, flank or abdominal pain, and progressive chronic kidney disease (CKD) advancing to end-stage kidney disease (ESKD). The average age at which ESKD manifests is about 58 years for men and 60-64 years for women. Extrarenal manifestations include hepatic cysts, which are the most common such manifestation, as well as intracranial aneurysms, cardiac valvular abnormalities, and seminal vesicle cysts. ARPKD typically presents in the perinatal, neonatal, or early childhood period with massive bilateral symmetrical renal enlargement, severe systemic hypertension, and congenital hepatic fibrosis.

ADPKD is the most common form of polycystic kidney disease with a prevalence of around 1:2,500. ARPKD is significantly less common, with an estimated incidence of approximately 1 in 20,000 live births.

ADPKD is caused by germline heterozygous pathogenic variants in PKD1 (~78%), PKD2 (~15%), IFT140 (~1.5%), and more rarely in GANAB, DNAJB11, ALG9 and ALG5 (each <0.5%). In most ARPKD cases, biallelic pathogenic variants in PKHD1 are identified as causative. In addition, variants in the DZIP1L gene have been identified in rare cases.

ADPKD is inherited in an autosomal dominant manner where an affected individual has a 50% chance of passing the pathogenic variant to each offspring. Approximately 10–15% of ADPKD cases result from de novo pathogenic variants with no family history. Autosomal recessive inheritance, as seen in ARPKD, requires a pathogenic variant to be inherited from each parent.

ADPKD is suspected on bilateral renal cysts together with a consistent family history. Kidney ultrasound shows excellent positive predictive value between 15 and 59 years; abdominal MRI is used when ultrasound findings are equivocal. For ARPKD, prenatal or neonatal ultrasonography characteristically shows bilaterally enlarged hyperechogenic kidneys with reduced corticomedullary differentiation.

Main differential diagnoses include:

• HNF1B-related kidney disease: cystic kidney disease often accompanied by maturity-onset diabetes of the young, pancreatic disease, hypomagnesaemia, hyperuricemia or congenital genitourinary anomalies
• : kidney angiomyolipomas with kidney cysts, hypomelanotic macules, cortical/subependymal tubers, cardiac rhabdomyomas and lymphangioleiomyomatosis
• Nephronophthisis-related ciliopathies: moderately enlarged cystic kidneys with cortical hyperechogenicity, prenatal oligo-/anhydramnios and early-childhood kidney failure

• Establishing the molecular genetic diagnosis where the clinical picture is suggestive but not yet conclusive, or where confirmation is required for further care planning.
• Enabling specific and individualised surveillance and clinical management – including imaging follow-up of kidney and liver cysts, blood pressure monitoring and screening for intracranial aneurysm where indicated.
• Allowing predictive testing of at-risk family members once the familial pathogenic variant has been identified.

• Harris PC, Torres VE. Polycystic kidney disease, autosomal dominant. 2002 Jan 10 [updated 2023]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. PMID:.
• Gunay-Aygun M. Autosomal recessive polycystic kidney disease. 2003 Dec 10 [updated 2021]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. PMID:.
• Torres VE, Ahn C, Barten TRM, et al. KDIGO 2025 clinical practice guideline for the evaluation, management, and treatment of autosomal dominant polycystic kidney disease (ADPKD): executive summary. Kidney Int. 2025;107(2):234-54. doi:10.1016/j.kint.2024.07.010. PMID:.