Tolvaptan is used in autosomal dominant polycystic kidney disease (ADPKD) to slow cyst growth. Its mechanism in ADPKD is:

• A Tolvaptan reduces intraglomerular pressure by blocking V1A receptors on afferent arterioles, slowing the hyperfiltration that drives cyst expansion
• B Tolvaptan blocks V2 receptors in collecting duct cells, reducing cAMP-mediated fluid secretion into cysts and inhibiting mTOR/cAMP-driven cyst epithelial cell proliferation ✓
• C Tolvaptan inhibits aquaporin-2 directly, preventing water transport into cysts through a non-receptor mechanism
• D Tolvaptan blocks arginine vasopressin binding to V3 receptors on renal tubular cells, preventing cystic hormone-driven expansion

Explanation

In ADPKD, mutated polycystin-1 or polycystin-2 (PC1/PC2) leads to elevated intracellular cAMP in cyst-lining epithelial cells, which drives both fluid secretion into cysts (via CFTR-mediated chloride secretion creating osmotic gradient) and cyst cell proliferation (via cAMP/PKA-MAPK/mTOR signaling). V2 receptor activation by vasopressin (AVP) is the primary cAMP source in collecting duct cells. Tolvaptan (a V2 receptor antagonist/vaptane) blocks AVP-V2 signaling, dramatically reducing cAMP, thereby inhibiting both fluid secretion and proliferation. TEMPO 3:4 and REPRISE trials confirmed slowing of total kidney volume growth and eGFR decline. Severe hepatotoxicity is a major concern requiring ALT/AST monitoring.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.