Mayo Clinic researchers discover vasopressin-independent kidney water pathway

Mayo Clinic researchers have discovered a previously unknown pathway that allows kidneys to concentrate urine independently of vasopressin, the hormone long considered the primary regulator of water retention, SciTechDaily reports. The finding, published 16 June 2026 in the Journal of Clinical Investigation, emerged during research into polycystic kidney disease (PKD) and could lead to new treatments that reduce side effects of the only approved PKD drug, tolvaptan. Led by nephrologist Fouad Chebib, the team found that probenecid, a 1940s gout medication, slowed cyst growth in PKD models rather than accelerating it as expected. Further study showed probenecid alters urate signaling, triggering water channels to move to cell surfaces without vasopressin. In preclinical research and a small clinical trial, adding probenecid reduced urine volume and patients experienced about a 30% reduction in urine output without diminishing tolvaptan's effectiveness. Patients went from waking several times nightly to once. Researchers are now developing therapies targeting this pathway more precisely than probenecid, which affects multiple biological systems.