Pathophysiology
Clinical meaning
In autosomal dominant polycystic kidney disease (ADPKD), dysfunctional polycystin proteins on renal tubular cell cilia cause decreased intracellular calcium, which activates adenylyl cyclase and increases cyclic AMP (cAMP). Elevated cAMP drives two pathological processes: cyst epithelial cell proliferation and chloride-driven fluid secretion into cyst lumens. Vasopressin (ADH) binding to V2 receptors on collecting duct cells amplifies this cAMP-mediated cystogenesis. Tolvaptan selectively blocks V2 receptors, reducing cAMP levels in cyst-lining cells and slowing both cyst growth and total kidney volume (TKV) expansion. The TEMPO 3:4 and REPRISE trials demonstrated tolvaptan reduces TKV growth rate and slows eGFR decline. However, hepatotoxicity is a significant risk requiring intensive liver function monitoring. The NP must carefully select candidates using Mayo Imaging Classification (Class 1C-1E predict rapid progression), assess ADPKD risk using PROPKD score (PKD1 truncating mutations, male sex, early hypertension, early urological events), and implement structured monitoring protocols.