A randomized trial of dietary sodium restriction in CKD

Abstract

There is a paucity of quality evidence regarding the effects of sodium restriction in patients with CKD, particularly in patients with pre-end stage CKD, where controlling modifiable risk factors may be especially important for delaying CKD progression and cardiovascular events. We conducted a double-blind placebo-controlled randomized crossover trial assessing the effects of high versus low sodium intake on ambulatory BP, 24-hour protein and albumin excretion, fluid status (body composition monitor), renin and aldosterone levels, and arterial stiffness (pulse wave velocity and augmentation index) in 20 adult patients with hypertensive stage 3-4 CKD as phase 1 of the LowSALT CKD study. Overall, salt restriction resulted in statistically significant and clinically important reductions in BP (mean reduction of systolic/diastolic BP, 10/4 mm Hg; 95% confidence interval, 5 to 15 /1 to 6 mm Hg), extracellular fluid volume, albuminuria, and proteinuria in patients with moderate-to-severe CKD. The magnitude of change was more pronounced than the magnitude reported in patients without CKD, suggesting that patients with CKD are particularly salt sensitive. Although studies with longer intervention times and larger sample sizes are needed to confirm these benefits, this study indicates that sodium restriction should be emphasized in the management of patients with CKD as a means to reduce cardiovascular risk and risk for CKD progression.

Figure 1.

Consolidated Standards of Reporting Trials diagram. Of the 25 patients who were randomized, 75% (n=20/25) completed the study and were included for analysis. Reasons for withdrawal were: visit schedule too demanding (n=3), hospital admission unrelated to study (n=1), and symptoms related to pre-existing condition (n=1).

Figure 2.

Effect of high sodium versus low sodium intake on BP values using 24-hour ambulatory BP monitoring. The central line denotes the median with the box indicating the interquartile range and whiskers indicating the range of change in BP measures from the high salt to the low salt period.

Figure 3.

Comparison of mean systolic BP values over 24 hours during high (▪) and low (▲) salt periods. Systolic BP was reduced consistently during the day (06:00–22:00 hours) and night (22:00–6:00 hours) periods.

Figure 4.

Median urinary protein/creatinine ratio (PCR) and albumin/creatinine ratio (ACR) during the high salt and low salt periods. Error bars indicate interquartile range.*P<0.01; **P<0.001 for difference from high salt period. PCR and ACR were significantly reduced on a low-sodium diet compared with a high-sodium diet.

Figure 5.

Relationship between change in systolic BP (SBP) and change in proteinuria (left) or albuminuria (right) from the high salt period to the low salt period.