Altered dietary salt intake for people with chronic kidney disease

Background Salt intake shows great promise as a modifiable risk factor for reducing heart disease incidence and delaying kidney function decline in people with chronic kidney disease (CKD). However, a clear consensus of the benefits of reducing salt in people with CKD is lacking. Objectives This review evaluated the benefits and harms of altering dietary salt intake in people with CKD. Search methods We searched the Cochrane Renal Group's Specialised Register to 13 January 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Selection criteria We included randomised controlled trials (RCTs) that compared two or more levels of salt intake in people with any stage of CKD. Data collection and analysis Two authors independently assessed studies for eligibility and conducted risk of bias evaluation. Results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Mean effect sizes were calculated using the random-effects models. Main results We included eight studies (24 reports, 258 participants). Because duration of the included studies was too short (1 to 26 weeks) to test the effect of salt restriction on endpoints such as mortality, cardiovascular events or CKD progression, changes in salt intake on blood pressure and other secondary risk factors were applied. Three studies were parallel RCTs and five were cross-over studies. Selection bias was low in five studies and unclear in three. Performance and detection biases were low in two studies and unclear in six. Attrition and reporting biases were low in four studies and unclear in four. One study had the potential for high carryover effect; three had high risk of bias from baseline characteristics (change of medication or diet) and two studies were industry funded. There was a significant reduction in 24 hour sodium excretion associated with low salt interventions (range 52 to 141 mmol) (8 studies, 258 participants: MD-105.86 mmol/d, 95% CI-119.20 to -92.51; I-2 = 51%). Reducing salt intake significantly reduced systolic blood pressure (8 studies, 258 participants: MD-8.75 mm Hg, 95% CI-11.33 to -6.16; I-2 = 0%) and diastolic blood pressure (8 studies, 258 participants: MD-3.70 mm Hg, 95% CI-5.09 to -2.30; I-2 = 0%). One study reported restricting salt intake reduced the risk of oedema by 56%. Salt restriction significantly increased plasma renin activity (2 studies, 71 participants: MD 1.08 ng/mL/h, 95% CI 0.51 to 1.65; I-2 = 0%) and serum aldosterone (2 studies, 71 participants: 6.20 ng/dL (95% CI 3.82 to 8.58; I-2 = 0%). Antihypertensive medication dosage was significantly reduced with a low salt diet (2 studies, 52 participants): RR 5.48, 95% CI 1.27 to 23.66; I-2 = 0%). There was no significant difference in eGFR (2 studies, 68 participants: MD-1.14 mL/min/1.73 m(2),95% CI-4.38 to 2.11; I 2 = 0%), creatinine clearance (3 studies, 85 participants): MD-4.60 mL/min, 95% CI-11.78 to 2.57; I-2 = 0%), serum creatinine (5 studies, 151 participants: MD 5.14 mu mol/L, 95% CI-8.98 to 19.26; I-2 = 59%) or body weight (5 studies, 139 participants: MD -1.46 kg; 95% CI-4.55 to 1.64; I-2 = 0%). There was no significant change in total cholesterol in relation to salt restriction (3 studies, 105 participants: MD -0.23 mmol/L, 95% CI -0.57 to 0.10; I-2 = 0%) or symptomatic hypotension (2 studies, 72 participants: RR 6.60, 95% CI 0.77 to 56.55; I-2 = 0%). Salt restriction significantly reduced urinary protein excretion in all studies that reported proteinuria as an outcome, however data could not be meta-analysed. Authors' conclusions We found a critical evidence gap in long-term effects of salt restriction in people with CKD that meant we were unable to determine the direct effects of sodium restriction on primary endpoints such as mortality and progression to end-stage kidney disease (ESKD). We found that salt reduction in people with CKD reduced blood pressure considerably and consistently reduced proteinuria. If such reductions could be maintained long-term, this effect may translate to clinically significant reductions in ESKD incidence and cardiovascular events. Research into the long-term effects of sodium-restricted diet for people with CKD is warranted, as is investigation into adherence to a low salt diet.