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 [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.

Intervention: Participants 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.

Outcome: The 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.

Measurements: Fasting plasma copeptin level, 24-hour urine osmolality, and total solute intake.

Results: Baseline 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.

Limitations: Small sample size and short follow-up.

Conclusions: We 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.

Keywords: Autosomal dominant polycystic kidney disease (ADPKD); clinical trial; copeptin; nutrition; osmolality; protein; salt; urea; vasopressin; water.

Figure 1

Consolidated Standards of Reporting Trials (CONSORT) diagram. Of the 34 patients who were randomized, 33 (97%) completed the study and were included for analysis. One patient withdrew participation, citing a conflict with a job.

Figure 2

Panel A: Plasma copeptin compared to baseline in the two study groups, over study visits. In the low osmolar diet group, plasma copeptin declined by 15% by visit 3 (week 2) (P=0.02), compared to non-significant change in the control group. Panel B: The primary outcome of the study was the change (delta) in copeptin between intervention and control groups from baseline to two weeks. This change was statistically significant (P=0.009). Plasma copeptin (pmol/L) in each individual patient in control (left) and intervention (right) groups before (visit 1) and after 2 weeks of assignment (visit 3). The bold solid line represents the mean. V, visit Panel C: In the intervention group, the 24 hour mean urine osmolality decreased by 40% on visit 3(week 2) (P=0.01) compared to no significant change in the control group during the study period. Panel D: The change (delta) in urine osmolality (mOsm/Kg H2O) between intervention and control groups at 2 weeks was statistically different (P=0.007). 24 hour urine osmolality in each individual patient in control (left) and intervention (right) groups before (visit 1) and after 2 weeks of treatment (visit 3). The bold solid line represents the mean. V, visit.

Figure 3

Change in total solute^a and corresponding water requirement^b at visit 2 needed to reach a target urine osmolality of 280 mOsm/Kg H₂O . Total solute was similar between groups at baseline (p= 0.3). Following intervention, total solute decreased only in the low osmolar diet group (P=0.02) reducing the mean water prescription for the intervention group from 3.2 L/daily at baseline to 2.6 L/daily at visit 2. ^a Total solute = urine volume (L) in 24 hours × urine osmolality (mOsm/Kg H₂O). ^b Including 0.5 liter for each individual to account for insensible loss.

Figure 4

Correlation between 24 hour urine osmolality (urine_osm) and fasting plasma copeptin. Plasma copeptin levels were directly correlated with 24 hour urine osmolality at baseline and throughout the study (Pearson’s r = 0.4, p<0.001).