Dataset Information

High water vs. ad libitum water intake for autosomal dominant polycystic kidney disease: a randomized controlled feasibility trial.

ABSTRACT:

Background

Vasopressin stimulates cyst growth in autosomal dominant polycystic kidney disease (ADPKD) and is a key therapeutic target. Evaluation of high water intake as an alternative to pharmacological vasopressin blockade is supported by patients. However feasibility, safety and adherence-promoting strategies required to deliver this remain unknown.

Aims

Assess the feasibility of a definitive randomized high water intake trial in ADPKD.

Methods

In this prospective open-label randomized trial, adult ADPKD patients with eGFR ? 20 ml/min/1.73 m2 were randomized to prescribed high water (HW) intake targeting urine osmolality (UOsm) ?270 mOsm/kg, or ad libitum (AW) intake (UOsm >300 mOsm/kg). Self-management strategies including home-monitoring of urine-specific gravity (USG) were employed to promote adherence.

Results

We enrolled 42 participants, baseline median eGFR (HW 68.4 [interquartile range (IQR) 35.9-107.2] vs. AW 75.8 [IQR 59.0-111.0 ml/min/1.73 m2, P = 0.22) and UOsm (HW 353 [IQR 190-438] vs. AW 350 [IQR 240-452] mOsm/kg, P = 0.71) were similar between groups. After 8 weeks, 67% in the HW vs. 24% in AW group achieved UOsm ?270 mOsm/kg, P = 0.001. HW group achieved lower UOsm (194 [IQR 190-438] vs. 379 [IQR 235-503] mOsm/kg, P = 0.01) and higher urine volumes (3155 [IQR 2270-4295] vs. 1920 [IQR 1670-2960] ml/day, P = 0.02). Two cases of hyponatraemia occurred in HW group. No acute GFR effects were detected. In total 79% (519/672) of USG were submitted and 90% (468/519) were within target. Overall, 17% withdrew during the study.

Conclusion

DRINK demonstrated successful recruitment and adherence leading to separation between treatment arms in primary outcomes. These findings suggest a definitive trial assessing the impact of high water on kidney disease progression in ADPKD is feasible.

SUBMITTER: El-Damanawi R

PROVIDER: S-EPMC7133783 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

High water vs. ad libitum water intake for autosomal dominant polycystic kidney disease: a randomized controlled feasibility trial.

El-Damanawi R R Lee M M Harris T T Cowley L B LB Bond S S Pavey H H Sandford R N RN Wilkinson I B IB Karet Frankl F E FE Hiemstra T F TF

QJM : monthly journal of the Association of Physicians 20200401 4

<h4>Background</h4>Vasopressin stimulates cyst growth in autosomal dominant polycystic kidney disease (ADPKD) and is a key therapeutic target. Evaluation of high water intake as an alternative to pharmacological vasopressin blockade is supported by patients. However feasibility, safety and adherence-promoting strategies required to deliver this remain unknown.<h4>Aims</h4>Assess the feasibility of a definitive randomized high water intake trial in ADPKD.<h4>Methods</h4>In this prospective open-l ...[more]

PMID: 31665476

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Project description:INTRODUCTION:Vasopressin stimulates cyst growth in autosomal dominant polycystic kidney disease (ADPKD) leading to enlarged kidneys, hypertension and renal failure. Vasopressin receptor blockade slows disease progression. Physiological suppression of vasopressin secretion through high water (HW) intake could achieve a similar effect, necessitating a definitive large-scale trial of HW intake in ADPKD. The objective of the DRINK trial is to answer the key design and feasibility questions required to deliver a successful definitive water intake trial. METHODS AND ANALYSIS:We describe the design of a single-centre, open-label, prospective, randomised controlled trial. The "Determining feasibility of R andomisation to high vs. ad libitum water In take in Polycystic K idney Disease" (DRINK) trial aims to enrol 50 patients with ADPKD, over the age of 16?years with an estimated glomerular filtration rate (eGFR) ?20?mL/min/1.73 m2. Participants will be randomised 1:1 to HW intake based on an individualised water intake prescription, or to ad libitum (AW) water intake. The HW group will aim for a dilute urine (urine osmolality ?270?mOsm/kg) as a surrogate marker of vasopressin suppression, and those in the AW group will target more concentrated urine. Participants will have an 8-week treatment period, and will be seen at weeks 0, 2, 4 and 8, undergoing assessments of fluid status, renal function and serum and urine osmolalities. They will receive dietary advice, and self-monitor urine specific gravity and fluid intake. The trial employs smartphone technology to permit home monitoring and remote direct data capture. The primary feasibility end points are recruitment rate and separation between arms in measured urinary osmolality. Key secondary assessments include acceptability, adherence, health-related quality of life, acute effects of HW intake on measured (51Cr-EDTA) and eGFR and ADPKD-related pain. ETHICS AND DISSEMINATION:Ethical approval was awarded by the East of England Essex Research Ethics Committee (16/EE/0026). The results of DRINK will be submitted to peer-reviewed journals, and presented to patients via the PKD Charity. TRIAL REGISTRATION NUMBER:NCT02933268 and ISCRTN16794957.

Project description:BackgroundAutosomal dominant polycystic kidney disease (ADPKD) affects millions of people worldwide. Vasopressin promotes disease progression.Study designA randomized controlled trial with equal (1:1) allocation.Setting & participantsThis trial examined the effect of combining a low-osmolar (low-sodium [1,500mg/d], low-protein [0.8g per kilogram of body weight]) diet and adjusted water intake on vasopressin secretion in 34 patients with ADPKD.InterventionParticipants were randomly assigned to receive a low-osmolar diet followed by adjusted water intake to achieve urine osmolality ≤ 280mOsm/kg water versus no intervention for 2 weeks.OutcomeThe primary outcome of the study was change (delta) in copeptin levels and urine osmolality between the intervention and control groups from baseline to 2 weeks.MeasurementsFasting plasma copeptin level, 24-hour urine osmolality, and total solute intake.ResultsBaseline characteristics of the 2 groups were similar. Mean plasma copeptin levels and urine osmolality declined from 6.2±3.05 (SD) to 5.3±2.5pmol/L (P=0.02) and from 426±193 to 258±117mOsm/kg water (P=0.01), respectively, in the intervention group compared to a nonsignificant change in the control group (from 4.7±3.6 to 5.07±4pmol/L [P=0.2] and 329±159 to 349±139mOsm/kg water [P=0.3], respectively). The change in copeptin levels (primary outcome) and urine osmolality was statistically significant between the intervention and control groups (delta copeptin, -0.86±1.3 vs +0.39±1.2pmol/L [P=0.009]; delta urine osmolality, -167±264 vs +20±80mOsm/kg water [P=0.007], respectively). Total urinary solute decreased in only the intervention group and significantly differed between groups at week 1 (P=0.03), reducing mean water prescription from 3.2 to 2.6L/d.LimitationsSmall sample size and short follow-up.ConclusionsWe developed a stepwise dietary intervention that led to a significant reduction in vasopressin secretion in patients with ADPKD. Furthermore, this intervention led to a reduction in water required for vasopressin reduction.

Dataset Information

High water vs. ad libitum water intake for autosomal dominant polycystic kidney disease: a randomized controlled feasibility trial.

Background

Aims

Methods

Results

Conclusion

Publications

High water vs. ad libitum water intake for autosomal dominant polycystic kidney disease: a randomized controlled feasibility trial.

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