autosomal dominant polycystic kidney disease

ADPKD is one of the most common inherited kidney disorders (1/400-1/1000 births) and a leading genetic cause of ESRD. Pathophysiology involves mutations in PKD1 (polycystin-1) or PKD2 (polycystin-2), proteins that localize to primary cilia and regulate calcium signaling, cell proliferation, and tubular differentiation. Loss of function leads to cyst formation from renal tubules, which progressively enlarge, compress normal parenchyma, and impair renal function via a 'two-hit' mechanism requiring a second somatic mutation. PKD1 mutations cause more severe disease with earlier progression to ESRD compared to PKD2. Clinical features include bilateral flank pain, hematuria, hypertension (often the earliest sign due to RAAS activation from cyst compression of vasculature), palpable bilateral flank masses, and recurrent UTIs. Extrarenal manifestations are key board-relevant associations: hepatic cysts (most common extrarenal manifestation), intracranial berry aneurysms (increased risk of subarachnoid hemorrhage - screen with MRA if family history of aneurysm/SAH), mitral valve prolapse, colonic diverticula, and abdominal wall/inguinal hernias. Diagnosis is typically via renal ultrasound showing multiple bilateral cysts, with age-specific criteria (e.g., ≥2 cysts if age <30, ≥4 cysts if age 30-59 unilateral or bilateral). Genetic testing can confirm diagnosis in ambiguous cases. Management is largely supportive: aggressive blood pressure control (ACE inhibitors/ARBs preferred), tolvaptan (vasopressin V2 receptor antagonist) may slow cyst growth and progression in select patients, pain management, and eventual dialysis or transplantation for ESRD. Distinguish from autosomal recessive PKD (ARPKD), which presents in infancy with Potter sequence, oligohydramnios, and hepatic fibrosis due to PKHD1 mutations.