Prescribed Water Intake in Autosomal Dominant Polycystic Kidney Disease

Résumé fourni par la source

Background: Arginine vasopressin (AVP) promotes kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). Increasing water intake to reduce urine osmolality and AVP release is hypothesized to slow kidney cyst growth in ADPKD. Methods: In this multi-center, open-label, parallel-arm randomized controlled 3-year trial adults with ADPKD and Mayo Subclass 1B to 1E and an estimated glomerular filtration rate (eGFR) of ≥30 mL per minute per 1.73m2, were randomized to water intake prescribed to reduce 24-hour urine osmolality to ≤270 mOsm/kg or ad libitum water intake irrespective of urine osmolality. The primary endpoint was the annualized rate of change in the height-corrected total kidney volume (Ht-TKV). Results: One hundred and eighty-four patients, with a mean 24-hour urine osmolality of 423±178 mOsm/kg and median 24-hour urine volume of 2.3L/day (IQR:1.8-3.1L/day) at baseline, were randomized to either ad libitum water intake (92 patients) or prescribed water intake (92 patients). Over 3 years the mean treatment differences between the ad libitum water and prescribed water intake groups for 24-hour urine osmolality and 24-hour urine volume were -91 mOsm/kg (95% CI -127 to -54 mOsm/kg;P<0.01) and 0.6L/day (95% CI 0.4 to 0.9L/day;P<0.01) respectively. The proportion of patients with 24-hour urine osmolality <300 mOsm/kg for >50% of timepoints was 52%. There was no difference in the percentage annualized rate of change in Ht-TKV between the groups (ad libitum water intake: 7.8% per year, 95% CI, 6.6 to 9.0%; prescribed water intake: 6.8% per year, 95% CI 5.8 to 7.7%; P=0.18). The decline in eGFR from baseline to 3 years, changes in other secondary endpoints, discontinuation rates and adverse events were comparable between the two groups. Conclusions: In ADPKD patients with a median baseline urine volume of 2.3L/day with Mayo subclass 1B to 1E, prescribed water intake was a safe intervention which achieved target urine osmolality in half of the patients but did not change the progression of total kidney volume over 3 years compared to ad libitum water intake. Funding: Commercial Support - Danone Research, Government Support - Non-U.S.

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