A Randomized Crossover Trial of Dietary Sodium Restriction in Stage 3-4 CKD

Abstract

Background and objectives: Patients with chronic kidney disease (CKD) are often volume expanded and hypertensive. Few controlled studies have assessed the effects of a sodium-restricted diet (SRD) in CKD.

Design, setting, participants, & measurements: We conducted a randomized crossover trial to evaluate the effect of SRD (target <2 g sodium per day) versus usual diet on hydration status (by bioelectrical impedance spectroscopy) and blood pressure (BP) between May of 2009 and May of 2013. A total of 58 adults with stage 3-4 CKD were enrolled from two academic sites: University of Michigan (n=37) and University of North Carolina at Chapel Hill (n=21); 60% were men, 43% were diabetic, 93% were hypertensive, and mean age was 61 years. Participants followed SRD or usual diet for 4 weeks, followed by a 2-week washout period and a 4-week crossover phase. During the SRD, dieticians provided counseling every 2 weeks, using motivational interviewing techniques.

Results: Whole-body extracellular volume and calf intracellular volume decreased by 1.02 L (95% confidence interval [95% CI], -1.48 to -0.56; P<0.001) and -0.06 L (95% CI, -0.12 to -0.01; P=0.02), respectively, implying decreased fluid content on the SRD compared with usual diet. Significant reductions in urinary sodium (-57.3 mEq/24 h; 95% CI, -81.8 to -32.9), weight (-2.3 kg; 95% CI, -3.2 to -1.5), and 24-hour systolic BP (-10.8 mmHg; 95% CI, -17.0 to -4.6) were also observed (all P<0.01). Albumin-to-creatinine ratio did not change significantly and mean serum creatinine increased slightly (0.1 mg/dl; 95% CI, -0.01 to 0.2; P=0.06). No period or carryover effects were observed. Results were similar when analyzed from phase 1 only before crossover, although P values were modestly larger because of the loss of power.

Conclusions: In this randomized crossover trial, implementation of SRD in patients with CKD stage 3-4 resulted in clinically and statistically significant improvement in BP and hydration status. This simple dietary intervention merits a larger trial in CKD to evaluate effects on major clinical outcomes.

Keywords: ambulatory blood pressure monitoring; bioelectrical impedance; crossover design; motivational interviewing; salt sensitivity.

Figure 1.

The experimental design is a randomized two-treatment two-period crossover design. Number of patients in each arm at each site during phase 1 (N_UM=37, N_UNC=21) and phase 2 (N_UM=35, N_UNC=21). At University of Michigan (UM), two patients withdrew in phase 1 because of illness unrelated to the intervention, and another withdrew because of competing priorities in phase 2 (n=34 completed). UNC, University of North Carolina at Chapel Hill.

Figure 2.

This diagram shows the patient flow through each phase of the randomized crossover trial. The study was conducted at the University of Michigan (A) and the University of North Carolina (B), following the guidelines of the Consolidated Standards of Reporting Trials. Of the 58 patients randomized, 29 (50%) were allocated to sodium-restricted diet (SRD) and 29 to usual diet in phase 1. The target sample size of 60 was on the basis of having 80% power to detect an effect size of 0.74 using a two-sample t test with 0.05, two-sided significance level.

Figure 3.

Sodium excretion at baseline is similar between treatment groups in both phases, but at Week 4 is lower in the sodium-restricted diet (SRD) than in usual diet in both phases (n=58). The length of the box defines the interquartile range (IQR). Medians are represented by horizontal lines and means by black dots. Outliers (values more than 1.5 times the IQR from either end of the box) are represented by circles. P value <0.05 indicates difference in 24-hour sodium excretion between treatment groups.

Figure 4.

Treatment effects (means and 95% confidence intervals [95% CIs]) for selected bioelectrical impedance spectroscopy (BIS) measurements were more favorable for those on the sodium-restricted versus usual diet. Values are plotted on different scales; results are reported on original scale. Results for all BIS measurements may be found in Supplemental Table 3.

Figure 5.

Compared to baseline in each phase, the sodium-restricted diet (SRD) group had significantly lower 24-hour systolic blood pressure (SBP) and significantly lower body weight than the usual diet group. Box plots of (A) change in 24-hour systolic BP (SBP), and (B) change in body weight in the combined study. The length of the box defines the interquartile range (IQR). Medians are represented by horizontal lines and means by black dots. Outliers (values more than 1.5 times the IQR from either end of the box) are represented by circles. Mean (SD) displayed.