Altered dietary salt intake for people with chronic kidney disease.

BACKGROUND: Evidence indicates that reducing dietary salt may reduce the incidence of heart disease and delay decline in kidney function in people with chronic kidney disease (CKD). This is an update of a review first published in 2015. OBJECTIVES: To evaluate the benefits and harms of altering dietary salt for adults with CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 6 October 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials comparing two or more levels of salt intake in adults with any stage of CKD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for eligibility, conducted risk of bias evaluation and evaluated confidence in the evidence using GRADE. Results were summarised using random effects models as risk ratios (RR) for dichotomous outcomes or mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: We included 21 studies (1197 randomised participants), 12 in the earlier stages of CKD (779 randomised participants), seven in dialysis (363 randomised participants) and two in post-transplant (55 randomised participants). Selection bias was low in seven studies, high in one and unclear in 13. Performance and detection biases were low in four studies, high in two, and unclear in 15. Attrition and reporting biases were low in 10 studies, high in three and unclear in eight. Because duration of the included studies was too short (1 to 36 weeks) to test the effect of salt restriction on endpoints such as death, cardiovascular events or CKD progression, changes in salt intake on blood pressure and other secondary risk factors were examined. Reducing salt by mean -73.51 mmol/day (95% CI -92.76 to -54.27), equivalent to 4.2 g or 1690 mg sodium/day, reduced systolic/diastolic blood pressure by -6.91/-3.91 mm Hg (95% CI -8.82 to -4.99/-4.80 to -3.02; 19 studies, 1405 participants; high certainty evidence). Albuminuria was reduced by 36% (95% CI 26 to 44) in six studies, five of which were carried out in people in the earlier stages of CKD (MD -0.44, 95% CI -0.58 to -0.30; 501 participants; high certainty evidence). The evidence is very uncertain about the effect of lower salt intake on weight, as the weight change observed (-1.32 kg, 95% CI -1.94 to -0.70; 12 studies, 759 participants) may have been due to fluid volume, lean tissue, or body fat. Lower salt intake may reduce extracellular fluid volume in the earlier stages of CKD (-0.87 L, 95% CI -1.17 to -0.58; 3 studies; 187 participants; low certainty evidence). The evidence is very uncertain about the effect of lower salt intake on reduction in antihypertensive dose (RR 2.45, 95% CI 0.98 to 6.08; 8 studies; 754 participants). Lower salt intake may lead to  symptomatic hypotension (RR 6.70, 95% CI 2.40 to 18.69; 6 studies; 678 participants; moderate certainty evidence). Data were sparse for other types of adverse events. AUTHORS' CONCLUSIONS: We found high certainty evidence that salt reduction reduced blood pressure in people with CKD, and albuminuria in people with earlier stage CKD in the short-term. If such reductions could be maintained long-term, this effect may translate to clinically significant reductions in CKD progression and cardiovascular events. Research into the long-term effects of sodium-restricted diet for people with CKD is warranted.

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 µmol/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.

Taste perception in kidney disease and relationship to dietary sodium intake.

Taste abnormalities are prevalent in Chronic Kidney Disease (CKD) potentially affecting food palatability and intake, and nutrition status. The TASTE CKD study aimed to assess taste and explore the relationship of dietary sodium intake with taste disturbance in CKD subjects. This was a cross-sectional study of 91 adult stage 3-5 CKD participants (78% male) aged 65.9 ± 13.5 years with mean estimated glomerular filtration rate of 33.1 ± 12.7 ml/min/1.73 m(2), and 30 controls (47% male) aged 55.2 ± 7.4 years without kidney dysfunction. Taste assessment was performed in both groups, presenting five basic tastes (sweet, sour, salty, umami and bitter) in blinded 2 ml solution which the participants tasted, identified (identification) and rated perceived strength (intensity) on a 10 cm visual analogue scale. Sodium intake was measured in the CKD group using validated food frequency questionnaire to determine high or low sodium intake (cut-off 100 mmol sodium/day). Differences between groups (CKD vs controls; high vs low sodium intake) were analysed using chi-square for identification and t-test for intensity. Multivariate analysis was used to adjust for age and gender differences between CKD and controls. The control group identified mean 3.9 ± 1.0 tastants correctly compared with 3.0 ± 1.2 for CKD group (p < 0.001), which remained significant after adjustment for age and gender. After adjustment for age and gender, sour identification and intensity and salty and umami intensity were impaired in CKD compared with controls. Participants with low sodium intake were more likely to correctly identify salty and umami, and rated intensity of umami and bitter significantly higher than those with high sodium intake. These findings add to the body of evidence suggesting that taste changes occur with CKD, independent of age and gender differences, with specific impairment in sour, umami and salty tastes. Our finding that sodium intake is related to umami and bitter disturbance as well as salty taste warrants further investigation.

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.

The effect of lowering salt intake on ambulatory blood pressure to reduce cardiovascular risk in chronic kidney disease (LowSALT CKD study): protocol of a randomized trial.

BACKGROUND: Despite evidence implicating dietary sodium in the pathogenesis of cardiovascular disease (CVD) in chronic kidney disease (CKD), quality intervention trials in CKD patients are lacking. This study aims to investigate the effect of reducing sodium intake on blood pressure, risk factors for progression of CKD and other cardiovascular risk factors in CKD. METHODS/DESIGN: The LowSALT CKD study is a six week randomized-crossover trial assessing the effect of a moderate (180 mmol/day) compared with a low (60 mmol/day) sodium intake on cardiovascular risk factors and risk factors for kidney function decline in mild-moderate CKD (stage III-IV). The primary outcome of interest is 24-hour ambulatory blood pressure, with secondary outcomes including arterial stiffness (pulse wave velocity), proteinuria and fluid status. The randomized crossover trial (Phase 1) is supported by an ancillary trial (Phase 2) of longitudinal-observational design to assess the longer term effectiveness of sodium restriction. Phase 2 will continue measurement of outcomes as per Phase 1, with the addition of patient-centered outcomes, such as dietary adherence to sodium restriction (degree of adherence and barriers/enablers), quality of life and taste assessment. DISCUSSION: The LowSALT CKD study is an investigator-initiated study specifically designed to assess the proof-of-concept and efficacy of sodium restriction in patients with established CKD. Phase 2 will assess the longer term effectiveness of sodium restriction in the same participants, enhancing the translation of Phase 1 results into practice. This trial will provide much-needed insight into sodium restriction as a treatment option to reduce risk of CVD and CKD progression in CKD patients. TRIAL REGISTRATION: Universal Trial Number: U1111-1125-2149. Australian New Zealand Clinical Trials Registry Number: ACTRN12611001097932.

Have renal dietitians successfully implemented evidence-based guidelines into practice? A survey of dietitians across Australia and New Zealand.

OBJECTIVE: Successful implementation of evidence-based practice (EBP) guidelines has been shown to improve the nutrition status of dialysis patients. This study aimed to establish use of EBP guidelines and implementation of key recommendations for nutrition assessment of dialysis patients, as well as to identify barriers and enablers associated with EBP guideline adherence. DESIGN: A survey of nutrition assessment practices and barriers to implementation of EBP guidelines was developed and piloted. The survey measured implementation of guidelines regarding frequency of nutrition assessment and use of the subjective global assessment (SGA) to diagnose malnutrition. Barriers to guideline implementation were measured using agreement with statements rated on a Likert scale. Data were summarized as counts and percentages and analyzed using chi-squared tests of association, with P < .05 indicating statistical significance. SETTING: The survey targeted specialist renal dietitians across Australian and New Zealand. PARTICIPANTS: Sixty-five renal dietitians from Australia and New Zealand responded to the survey. Most were females (89%, n = 58 of 65), aged <35 years (72%, n = 47 of 65), with one-third (n = 22 of 65) working in renal dietetics for longer than 4 years. RESULTS: Nearly all participants (n = 62 of 65) reported routinely using EBP guidelines; however, only 55% and 66% indicated they had successfully implemented the guidelines regarding minimum 6-monthly nutrition assessment of dialysis patients (n = 36 of 65) and use of the SGA (n = 43 of 65), respectively. Barriers related to time, skills/self-efficacy, and an inefficient referral system were related to lower rates of guideline implementation. CONCLUSION: These findings indicate an evidence-practice gap in the nutritional management of dialysis patients. A standardized approach to EBP guideline implementation including structured 6-monthly nutrition assessment of dialysis patients and group training for use of the SGA tool may assist in closing this evidence-practice gap.

Achieving salt restriction in chronic kidney disease.

There is consistent evidence linking excessive dietary sodium intake to risk factors for cardiovascular disease and chronic kidney disease (CKD) progression in CKD patients; however, additional research is needed. In research trials and clinical practice, implementing and monitoring sodium intake present significant challenges. Epidemiological studies have shown that sodium intake remains high, and intervention studies have reported varied success with participant adherence to a sodium-restricted diet. Examining barriers to sodium restriction, as well as factors that predict adherence to a low sodium diet, can aid researchers and clinicians in implementing a sodium-restricted diet. In this paper, we critically review methods for measuring sodium intake with a specific focus on CKD patients, appraise dietary adherence, and factors that have optimized sodium restriction in key research trials and discuss barriers to sodium restriction and factors that must be considered when recommending a sodium-restricted diet.