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Water prescription in autosomal dominant polycystic kidney disease: a pilot study.

ABSTRACT: In animal models of polycystic kidney disease, the ingestion of large amounts of water promotes diuresis by suppressing plasma levels of arginine vasopressin (AVP) and renal levels of cAMP, slowing cyst progression. Whether simple water ingestion is a potential therapeutic strategy for individuals with autosomal dominant polycystic kidney disease (ADPKD) is unknown. In this study, a simple method to quantify the amount of water to achieve a specific mean urine osmolality target in patients with ADPKD was developed and tested.In eight ADPKD patients eating typical diets, osmolality and volume were measured in 24-hour urine collections. The amount of additional ingested water required daily to achieve a mean urine osmolality of 285 ± 45 mosm/kg was determined. Participants were instructed to distribute the prescribed water over waking hours for each of 5 days. Blood chemistries, 24-hour urine collections, BP, and weight were measured before and after the period of supplemental water intake.Five patients achieved the 285 mosm/kg urine target without difficulty. Mean urine osmolality decreased and mean urine volume increased; serum sodium, weight, and BP were unchanged. Daily osmolar excretion remained constant, indicating a stable ad lib dietary intake of solutes and protein over the 2-week study period.The amount of additional water needed to achieve a urine osmolality target can be approximated from the urine osmolar excretion in ADPKD patients eating typical diets, providing a quantitative method to prescribe supplemental water for such individuals.

SUBMITTER: Wang CJ

PROVIDER: S-EPMC3022242 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Water prescription in autosomal dominant polycystic kidney disease: a pilot study.

Wang Connie J CJ Creed Catherine C Winklhofer Franz T FT Grantham Jared J JJ

Clinical journal of the American Society of Nephrology : CJASN 20100928 1

<h4>Background and objectives</h4>In animal models of polycystic kidney disease, the ingestion of large amounts of water promotes diuresis by suppressing plasma levels of arginine vasopressin (AVP) and renal levels of cAMP, slowing cyst progression. Whether simple water ingestion is a potential therapeutic strategy for individuals with autosomal dominant polycystic kidney disease (ADPKD) is unknown. In this study, a simple method to quantify the amount of water to achieve a specific mean urine o ...[more]

PMID: 20876670

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Project description:BACKGROUND:Metformin has shown promising results regarding cystogenesis inhibition in preclinical studies with autosomal dominant polycystic kidney disease (ADPKD) models. We designed a prospective, preliminary, single-arm study to evaluate the tolerability, safety and the effect of Metformin on kidney function and body mass index (BMI) in Romanian patients with ADPKD. METHODS:We enrolled 34 adult patients with ADPKD, chronic kidney disease (CKD) stages 1-5 not on dialysis and without diabetes mellitus. The primary endpoint was to assess the tolerability and safety of Metformin. The secondary endpoints evaluated changes in estimated glomerular filtration rate (eGFR), body mass index (BMI) and renal replacement therapy (RRT) necessity. Patients received an initial dose of Metformin of 500?mg/day within the first month that was increased to 1000?mg/day thereafter according to tolerability. Change in eGFR and BMI was expressed as mean difference with the corresponding 95% confidence intervals and as a percentage. For the primary endpoint, we included all 34 enrolled patients. To assess the secondary endpoint, intention-to-treat (ITT) and per-protocol (PP) analysis was performed. RESULTS:Sixteen patients out of 34 completed the follow-up period at 24?months. Eighteen patients developed adverse events and 63.6% of these events were gastrointestinal related. Nausea was the most common adverse event (17.6%). Two patients (5.8%) permanently discontinued medication due to adverse events. We recorded no case of hypoglycemia, lactic acidosis or death. Mean eGFR changed by -?1.57?ml/min/1.73m2 (95%CI:-22.28 to 19.14, P =?0.87) in ITT and by -?4.57?ml/min/1.73m2 (95%CI:-28.03 to 18.89, P =?0.69) in PP population. Mean BMI change was -?1.10?kg/m2 (95%CI:-3.22 to 1.02, P =?0.30) in ITT population and?-?0.80?kg/m2 (95%CI:-3.27 to 1.67, P =?0.51) in PP analysis. Three patients (8.8%) needed RRT. CONCLUSIONS:Metformin was well tolerated, had a good safety profile even in ADPKD patients with advanced CKD and it was not associated with change in eGFR or BMI across the follow-up period. TRIAL REGISTRATION:The study was retrospectively registered on https://www.isrctn.com (number ISRCTN 93749377); date registered: 02/25/2019.

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Water prescription in autosomal dominant polycystic kidney disease: a pilot study.

Publications

Water prescription in autosomal dominant polycystic kidney disease: a pilot study.

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