A Randomized Trial of Dietary Sodium Restriction in CKD

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.Cardiovascular disease (CVD) is the leading cause of premature mortality in the CKD population.^1,2 CVD risk increases with only mild kidney impairment (estimated GFR [eGFR] <60 ml/min per 1.73 m²) and further escalates as CKD progresses,³ making early intervention to reduce CVD risk of utmost importance.⁴Dietary sodium intake shows great promise as a modifiable risk factor for reducing the risks of cardiovascular disease and CKD progression.^5,6 Extensive research has demonstrated the effect of sodium intake on fluid overload and hypertension,^7,8 which are predictors of cardiac and vascular remodeling.⁹ Trials in sodium restriction recently showed significant reductions in proteinuria and albuminuria,^7,10,11 which are strong predictors of CKD progression and CVD events.¹² In addition, excessive sodium intake is thought to have direct toxic effects on blood vessels through mediating factors such as oxidative stress, inflammation, endothelial cell dysfunction, and vascular stiffness.^13–15The available evidence detailing the effects of sodium restriction in CKD patients is of poor quality, lacks randomization,^16–18 a control group,¹⁷ or blinding,^10,11 or does not use gold-standard measurement techniques (e.g., using clinic instead of ambulatory BP).^10,11 Furthermore, several studies failed to either evaluate or adjust for the influence of key confounding factors, such as potassium intake or body weight,^{10,11,19–22} thereby making it difficult to assess whether the observed results can be solely attributed to dietary sodium.The aim of this double-blind placebo-controlled randomized crossover study was to evaluate the effects of dietary sodium intake on BP, proteinuria, extracellular fluid volume, and arterial stiffness as markers of risks of cardiovascular and CKD progression. We hypothesized that a low sodium intake would decrease 24-hour BP, fluid volume, and 24-hour urinary protein and albumin compared with high sodium intake in patients with moderate-to-severe CKD.