Low-Osmolar Diet and Adjusted Water Intake for Vasopressin Reduction in Autosomal Dominant Polycystic Kidney Disease: A Pilot Randomized Controlled Trial

Abstract

Background Autosomal dominant polycystic kidney disease (ADPKD) affects millions of people worldwide. Vasopressin promotes disease progression. Study Design A randomized controlled trial with equal (1:1) allocation. Setting & Participants This trial examined the effect of combining a low osmolar (low-sodium [1500 mg/d], low-protein [0.8 g per kilogram of body weight]) diet and adjusted water intake on vasopressin in 34 ADPKD patients. Intervention Participants were randomized to receive a low osmolar diet followed by adjusted water intake to achieve a urine osmolality of ≤280 mOsm/kg H2O versus no intervention for two weeks. Outcome The primary outcome of the study was the change (delta) in copeptin and urine osmolality between intervention and control groups from baseline to two weeks Measurements Fasting plasma copeptin, 24 hour urine osmolality, and total solute intake Results Baseline characteristics of the two groups were similar. Mean plasma copeptin and urine osmolality declined from 6.2 ±3.05 (SD) to 5.3± 2.5 pmol/L (P=0.02) and from 426 ±193 to 258 ±117 mOsm/Kg H2O (P=0.01), respectively, in the intervention group compared to a non-significant change in the control group (4.7 ±3.6 to 5.07 ±4 pmol/L [P=0.2] and from 329 ±159 to 349 ±139 mOsm/kg H2O [P=0.3], respectively). The change in copeptin (primary outcome) and urine osmolality was statistically significant between intervention and control groups (delta copeptin, −0.86 ±1.3 versus +0.39 ±1.2 pmol/L [P=0.009]; delta urine osmolality, −167±264 versus +20±80 mOsm/Kg H2O [P=0.007], respectively). Total urinary solute decreased only in the intervention group and significantly differed between groups at week one (P=0.03) reducing mean water prescription from 3.2 to 2.6 L/day. Limitations Small sample size and short follow up duration. Conclusions We developed a step-wise dietary intervention that led to significant reduction in vasopressin in ADPKD patients. Furthermore, this intervention led to reduction in water required for vasopressin reduction.

A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan

“…Dietary changes that reduce daily osmolar loads, such as moderate reductions in the ingestion of protein and sodium, help to reduce the aquaretic effect. 54 Tolvaptan should be held and hydration increased during intercurrent illnesses that lead to dehydration or interfere with adequate hydration, such as food poisoning and gastroenteritis; when conditions such as outdoor activities in warm weather increase insensible water loss; and when water access is restricted, such as during travel and social events. Tolvaptan should also be held 24-48 hours before elective surgeries and not be restarted until the patients are able to maintain adequate hydration.…”

International consensus statement on the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people

“…Dehydration should therefore be avoided, and patients should be encouraged to drink to satisfy thirst 108 . A low-osmolar diet (low sodium, low protein and adjusted water intake to decrease urinary osmolality to <280 mOsM/kg (280 mmol/kg)) decreased the levels of endogenous copeptin (a surrogate marker of vasopressin) in a short study of adults with ADPKD, but a potential long-term benefit on cyst growth remains speculative 109 . In children with non-ADPKD CKD, an RCT did not find a beneficial effect of a low-protein diet on GFR decline 110 .…”

Osmoregulation in Polycystic Kidney Disease: Relationship with Cystogenesis and Hypertension

“…Increasing fluid intake was found to effectively impair renal cystogenesis in rodents [7] and has been shown to effectively decrease plasma copeptin levels in patients [14]. Though a single clinical trial did not find a beneficial effect of increasing water intake in a small cohort of ADPKD patients [15], other clinical trials with a larger number of participants and a longer treatment duration are currently underway (e.g., PREVENT-PKD trial; ACTRN12614001216606).…”