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

Abstract

In animal models of ADPKD, high water intake (HWI) decreases vasopressin secretion and slows disease progression, but the efficacy of HWI in human ADPKD is uncertain. This exploratory, prospective, crossover study of ADPKD subjects (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. Subjects 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), MRI measurements of htTKV, and pain survey responses were compared between HWI and UWI. During HWI, mean 24-hour Uosm decreased compared to UWI (428 [398-432] mOsm/kg vs. 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 pmol/L 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), pain occurrence and pain interference during sleep (p<0.01). HWI was well tolerated. 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 non-pharmacologic treatment of ADPKD.