Randomised controlled trial to determine the efficacy and safety of prescribed water intake to prevent kidney failure due to autosomal dominant polycystic kidney disease (PREVENT-ADPKD)

Abstract

IntroductionMaintaining fluid intake sufficient to reduce arginine vasopressin (AVP) secretion has been hypothesised to slow kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). However, evidence to support this as a clinical practice recommendation is of poor quality. The aim of the present study is to determine the long-term efficacy and safety of prescribed water intake to prevent the progression of height-adjusted total kidney volume (ht-TKV) in patients with chronic kidney disease (stages 1–3) due to ADPKD.Methods and analysisA multicentre, prospective, parallel-group, open-label, randomised controlled trial will be conducted. Patients with ADPKD (n=180; age ≤65 years, estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2) will be randomised (1:1) to either the control (standard treatment+usual fluid intake) or intervention (standard treatment+prescribed fluid intake) group. Participants in the intervention arm will be prescribed an individualised daily fluid intake to reduce urine osmolality to ≤270 mOsmol/kg, and supported with structured clinic and telephonic dietetic review, self-monitoring of urine-specific gravity, short message service text reminders and internet-based tools. All participants will have 6-monthly follow-up visits, and ht-TKV will be measured by MRI at 0, 18 and 36 months. The primary end point is the annual rate of change in ht-TKV as determined by serial renal MRI in control vs intervention groups, from baseline to 3 years. The secondary end points are differences between the two groups in systemic AVP activity, renal disease (eGFR, blood pressure, renal pain), patient adherence, acceptability and safety.Ethics and disseminationThe trial was approved by the Human Research Ethics Committee, Western Sydney Local Health District. The results will inform clinicians, patients and policy-makers regarding the long-term safety, efficacy and feasibility of prescribed fluid intake as an approach to reduce kidney cyst growth in patients with ADPKD.Trial registration numberANZCTR12614001216606.

Barriers and facilitators for recruiting and retaining male participants into longitudinal health research: a systematic review

“… # Odds ratio reported only for male participants retained [ 39 ] or division of age groups [ 59 ] * Data not divided between those identifying as men and those who identify as women a Study protocol of PREVENT ADPKD [ 63 ], substudy visits not specified [ 38 ] but is assumed 2 (questionnaire, interview) in a 16 month period b [ 40 ] and study protocol [ 60 ]. Study launched reported on study website [ 64 ] c Protocol paper describes 3 Stages after recruiting a population-based cohort [ 60 ], not described in [ 40 ] d Study contact were text messages the amount, timing and frequency of SMS text messages were decided by participant [ 44 ] e Completers of final postal survey f Last wave (wave 5) of the study (77 – 87 years old) completers of follow-up, no male specific data given for wave 1–4 [ 45 ] g Protocol paper describes the use of census data at 1996, 2001 and 2006 [ 65 ] h Yearly visits with an option to fill in a complementary questionnaire each month [ 43 ] i Two studies were included WebMOVE and MOVE-SMI [ 53 ] j Sub-study was randomly selected from WebMOVE and MOVE-SMI groups and not stratified by sex [ 53 ] k Details only recruitment strategies [ 54 ] l Due to its longitudinal nature, it is assumed this study has more than 3 visits in the 12-year reported period.…”

“…a Study protocol of PREVENT ADPKD [ 63 ], substudy visits not specified [ 38 ] but is assumed 2 (questionnaire, interview) in a 16 month period…”

Emerging non-pharmacological interventions in ADPKD: an update on dietary advices for clinical practice

“…A smaller study including 32 participants looks at change in total kidney volume after 1 year (NCT03102632) and a larger study, consisting of 180 ADPKD patients who will be randomized to control (usual fluid intake) or intervention (individualized daily fluid intake to reduce osmolality to ≤270 mOsmol/kg) during 36 months. End points will be change in total kidney volume and estimated GFR [69]. Until results of these studies become available, the question is what to advise to ADPKD patients.…”

New Options in ADPKD and How to Use them–the PROPKD Score and Beyond

“…Since increased fluid intake results in suppression of vasopressin this approach is patho-physiologically quite similar to tolvaptan therapy (vasopressin receptor blockade). A recently launched prospective trial aims at exactly this similarity [9]: in a randomized multi-centre trial 180 ADPKD patients with a residual GFR ≥ 30 mL/min/1.73 m 2 will be treated with either standard therapy and uncontrolled fluid intake or standard therapy and an individualized, prescribed and controlled fluid intake strictly lowering the urine osmolality below 270 mOsmol/kg.…”