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

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

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 non-pharmacologic treatment of ADPKD.