Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Introduction to ADPKD

ADPKD is a genetically inherited disorder characterized by progressive development of bilateral kidney cysts caused by mutations in PKD1 or PKD2 genes, leading to kidney enlargement and eventual kidney failure in adulthood 1
The American College of Nephrology recommends considering the genetic basis of ADPKD, with PKD1 mutations accounting for approximately 85% of cases and PKD2 mutations accounting for approximately 15% of cases 1

Mutations in the PKD1 gene (chromosome 16) account for approximately 85% of ADPKD cases, encoding polycystin-1 (PC1), a large membrane receptor protein, with truncating mutations causing more severe disease and non-truncating mutations causing variable disease severity 1
Mutations in the PKD2 gene (chromosome 4) account for approximately 15% of ADPKD cases, encoding polycystin-2 (PC2), a non-selective cation channel permeable to Ca²⁺, generally resulting in milder disease 1
Minor genes, such as IFT140, ALG5, ALG9, GANAB, DNAJB11, and NEK8, account for a small percentage (<5%) of ADPKD cases with variable phenotypes 1

Bilateral kidney enlargement with multiple cysts, hypertension, progressive decline in kidney function, and kidney pain are common manifestations of ADPKD 1
Extrarenal manifestations, including liver cysts, intracranial aneurysms, and cardiac valve abnormalities, can also occur in ADPKD patients 1

Disease severity varies based on genotype, with PKD1 mutations generally causing more severe disease than PKD2 mutations, and truncating PKD1 mutations typically causing more severe disease than non-truncating mutations 1
Sex and environmental factors, such as obesity and high salt intake, can also influence disease progression, with males generally progressing more rapidly than females 1

Current therapeutic approaches target specific pathophysiologic mechanisms, including the use of vasopressin V2 receptor antagonists, such as tolvaptan, to reduce cAMP levels and decrease fluid secretion and cell proliferation 1