Feasibility of Water Therapy for Slowing Autosomal Dominant Polycystic Kidney Disease Progression

Background In animal models of autosomal dominant polycystic kidney disease (ADPKD), high water intake (HWI) decreases vasopressin secretion and slows disease progression, but the efficacy of HWI in human ADPKD is uncertain. Methods This exploratory, prospective, cross-over study of patients with ADPKD (N=7) evaluated the hypothesis that HWI slows the rate of increase in height-adjusted total kidney volume (ht-TKV; a biomarker for ADPKD progression) and reduces pain. Patients at high risk of ADPKD progression (i.e., Mayo Imaging Classifications 1C/1D) were evaluated during 6 months of usual water intake (UWI), followed by 12 months of HWI calculated to reduce urine osmolality (Uosm) to <285 mOsm/kg. Measurements of Uosm, serum copeptin (secreted in equimolar amounts with vasopressin), magnetic resonance imaging measurements of ht-TKV, and pain survey responses were compared between HWI and UWI. Results During HWI, mean 24-hour Uosm decreased compared with UWI (428 [398-432] mOsm/kg versus 209 [190-223] mOsm/kg; P = 0.01), indicating adherence to the protocol. Decreases during HWI also occurred in levels of serum copeptin (5.8 +/- 2.0 to 4.2 +/- 1.6 pmol/L; P = 0.03), annualized rate of increase in ht-TKV (6.8% [5.9-8.5] to 4.4% [3.0-5.0]; P < 0.02), and pain occurrence and pain interference during sleep (P < 0.01). HWI was well tolerated. Conclusions HWI in patients at risk of rapid progression of ADPKD slowed the rate of ht-TKV growth and reduced pain. This suggests that suppressing vasopressin levels by HWI provides an effective nonpharmacologic treatment of ADPKD.