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

• A Inhibition of mTOR signaling in renal tubular cells, reducing cyst epithelial proliferation
• B Selective V2 vasopressin receptor antagonism, reducing cAMP-driven cyst fluid secretion and epithelial proliferation ✓
• C Aldosterone receptor blockade, reducing sodium and water retention in cysts
• D Blocking chloride cotransporter NKCC2, reducing cyst fluid accumulation

Explanation

Tolvaptan is a selective, competitive V2 vasopressin receptor antagonist. In ADPKD, vasopressin acting on V2 receptors elevates intracellular cAMP in renal tubular epithelium, driving both cyst epithelial proliferation and chloride-driven fluid secretion into cysts. Tolvaptan blocks V2 receptors, reducing cAMP and slowing cyst growth. The TEMPO 3:4 and REPRISE trials demonstrated it significantly slows total kidney volume increase and eGFR decline. Its main serious adverse effect is hepatotoxicity requiring 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.