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High Versus Ad Libitum Water Intake in Patients with Autosomal Dominant Polycystic Kidney Disease (DRINK): An Open Label, Randomised Controlled Phase 2 Trial

78 Pages Posted: 6 Dec 2018

See all articles by Ragada El-Damanawi

Ragada El-Damanawi

University of Cambridge - Cambridge Clinical Trials Unit

Michael Lee

University of Cambridge

Tess Harris

PKD Charity

Laura B. Mader

University of Cambridge - Cambridge Clinical Trials Unit

Simon Bond

University of Cambridge - Cambridge Clinical Trials Unit

Holly Pavey

University of Cambridge - Cambridge Clinical Trials Unit

Richard N. Sandford

University of Cambridge - Department of Medical Genetics

Ian B. Wilkinson

University of Cambridge - Cambridge Clinical Trials Unit; University of Cambridge - Experimental Medicine and Immunotherapeutics (EMIT)

Alison Burrows

University of Bristol

Przemyslaw Woznowski

University of Bristol

Yoav Ben-Shlomo

University of Bristol - Department of Population Health Sciences

Fiona E Karet Frankl

University of Cambridge - Department of Medical Genetics

Thomas F. Hiemstra

University of Cambridge - Cambridge Clinical Trials Unit

More...

Abstract

Background: Vasopressin promotes cyst growth in Autosomal Dominant Polycystic Kidney Disease (ADPKD). Vasopressin receptor antagonists slow disease progression, but their use is limited by side effects and cost. High water intake suppresses vasopressin production and may provide a viable alternative to pharmacological receptor blockade. We aimed to assess the feasibility of a definitive randomised high water intake trial in ADPKD.

Methods: We conducted a phase 2, single-centre open-label randomised controlled trial (NCT02933268). Adults aged 16 years and older with ADPKD and an eGFR20ml/min/1.73m2 were randomly assigned to prescribed high water intake (HW) targeting a urine osmolality of 270mOsm/kg, or ad libitum (AW) intake. The co-primary outcomes were the proportion of participants achieving target urine osmolality and the rate of recruitment. Secondary outcomes included separation between treatment arms, changes in GFR, copeptin, and safety.

Findings: 42 participants with a median baseline eGFR 75.8 (IQR 46.5-107.5) ml/min/1.73m2 and urine osmolality 352 (IQR 202-452) mOsm/Kg were enrolled over 12 months and randomised to HW (n=21) or AW (n=21). After 8 weeks, 67% in the HW compared to 24% in the AW group had a urine osmolality of 270mOsm/kg, p=0.001. The median week-8 urine osmolality was significantly higher in the AW compared to HW group (379 IQR 235-503 v 194 IQR 190-438 mOsm/kg, p=0.01). There was no difference in median week 8 plasma copeptin (AW=4.1, IQR 2.9-11.2 vs HW=3.6, IQR 2.7-5.7, p=0.25) and no evidence of acute effects of increased hydration on measured or estimated GFR.

Interpretation: It is possible to recruit to and achieve separation between trial arms in urine osmolality in a randomised trial. A definitive trial assessing the effect of high water intake on kidney
function in ADPKD is feasible.

Clinical Trial Number: NCT02933268

Funding Statement: The study is funded by the British Renal Society and Kidney Care UK (formerly British Kidney Patient Association) grant programme, the PKD Charity, the Addenbrooke’s Charitable Trust and Kidney Research UK.

Declaration of Interests: None declared

Ethics Approval Statement: DRINK was approved by the East of England Essex Research Committee (16/EE/0026) and the study was overseen by the trial steering committee.

Suggested Citation

El-Damanawi, Ragada and Lee, Michael and Harris, Tess and Mader, Laura B. and Bond, Simon and Pavey, Holly and Sandford, Richard N. and Wilkinson, Ian B. and Burrows, Alison and Woznowski, Przemyslaw and Ben-Shlomo, Yoav and Frankl, Fiona E Karet and Hiemstra, Thomas F., High Versus Ad Libitum Water Intake in Patients with Autosomal Dominant Polycystic Kidney Disease (DRINK): An Open Label, Randomised Controlled Phase 2 Trial (November 28, 2018). Available at SSRN: https://ssrn.com/abstract=3294762 or http://dx.doi.org/10.2139/ssrn.3294762

Ragada El-Damanawi (Contact Author)

University of Cambridge - Cambridge Clinical Trials Unit ( email )

Box 157
Hills Rd
Cambridge, CB2 0QQ
United Kingdom

Michael Lee

University of Cambridge

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

Tess Harris

PKD Charity

London
United Kingdom

Laura B. Mader

University of Cambridge - Cambridge Clinical Trials Unit

Box 157
Hills Rd
Cambridge, CB2 0QQ
United Kingdom

Simon Bond

University of Cambridge - Cambridge Clinical Trials Unit

Box 157
Hills Rd
Cambridge, CB2 0QQ
United Kingdom

Holly Pavey

University of Cambridge - Cambridge Clinical Trials Unit

Box 157
Hills Rd
Cambridge, CB2 0QQ
United Kingdom

Richard N. Sandford

University of Cambridge - Department of Medical Genetics

Cambridge, CB2 0XY
United Kingdom

Ian B. Wilkinson

University of Cambridge - Cambridge Clinical Trials Unit

Box 157
Hills Rd
Cambridge, CB2 0QQ
United Kingdom

University of Cambridge - Experimental Medicine and Immunotherapeutics (EMIT)

Cambridge
United Kingdom

Alison Burrows

University of Bristol

University of Bristol,
Senate House, Tyndall Avenue
Bristol, BS8 ITH
United Kingdom

Przemyslaw Woznowski

University of Bristol

University of Bristol,
Senate House, Tyndall Avenue
Bristol, BS8 ITH
United Kingdom

Yoav Ben-Shlomo

University of Bristol - Department of Population Health Sciences

Tyndall Avenue, Senate House
Bristol, BS8 1TH
United Kingdom

Fiona E Karet Frankl

University of Cambridge - Department of Medical Genetics

Cambridge, CB2 0XY
United Kingdom

Thomas F. Hiemstra

University of Cambridge - Cambridge Clinical Trials Unit

Box 157
Hills Rd
Cambridge, CB2 0QQ
United Kingdom

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