Randomised controlled trial of high versus ad libitum water intake in patients with autosomal dominant polycystic kidney disease: rationale and design of the DRINK feasibility trial

Abstract

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.

Keywords: autosomal dominant polcystic kidney disease; feasibility; osmolality; urine specific gravity; vasopressin; water.

Figure 1

Schematic of the DRINK trial design. Participants are randomised 1:1 to the high water (HW) or ad libitum (AW) water intake groups. Each participant in the HW group is given an individualised daily water prescription with urinary dilution targets consistent with vasopressin suppression. The AW group has more concentrated urinary targets. ADPKD, autosomal dominant polycystic kidney disease; uSG, urine specific gravity.

Figure 2

Smartphone technology used during the DRINK study. The SPLASH app uses near field communication technology to automate fluid intake monitoring (left). The DRINK app will be used to record urine specific gravity results allowing remote data collection and monitoring of progress (right).

Figure 3

Calculation of fluid prescription using the free water clearance equation. Insensible losses were arbitrarily set at 500 mL as an average.