Dietary Sodium Restriction in the Management of Chronic Kidney Disease: A Meta-Analysis of RCTs

Research Article

Austin J Nephrol Hypertens. 2021; 8(2): 1098.

Dietary Sodium Restriction in the Management of Chronic Kidney Disease: A Meta-Analysis of RCTs

Sai Sidharth M¹* and Dhar M²

1Associate Data Scientist, Centre for Open Data Research (CODR) - Public Affairs Centre (PAC), India

2Professor, Department of Bio-Statistics and Epidemiology, International Institute for Population Sciences (IIPS), India

*Corresponding author: Sai Sidharth M, Associate Data Scientist, Centre for Open Data Research (CODR) - Public Affairs Centre (PAC), Bengaluru, India

Received: September 06, 2021; Accepted: October 08, 2021; Published: October 15, 2021


Introduction: Non-pharmacological strategies such as lowering sodium intake aim to protect renal function and delay the initiation of renal replacement therapy. It might also be a cost-effective method to improve Chronic Kidney Disease (CKD) prognosis. We decided to perform a meta-analysis of Randomized Controlled Trials (RCTs) to evaluate the effects of low versus high sodium intake in adults with CKD.

Methodology: We searched the online databases – PUBMED, Cochrane Kidney and Transplant Specialized Register, Cochrane Library and Google Scholar to 31st December 2020 for RCTs to be included in the study. Meta- Analysis was performed for the intervention groups for each arm against the control. Inverse variance methods were applied for analysis using random effects models due to the high heterogeneity among the studies.

Results: Our search strategy yielded seven studies from six countries with 465 participants. The overall effect on restricted sodium intake favored reduction in systolic blood pressure with an overall mean difference of -6.14(95% CI: -9.52, -2.76) and reduction in diastolic blood pressure with a mean difference of -3.08 (95% CI: -4.62, -1.55). There was lowering of estimated Glomerular Filtration Rate (eGFR), however the same was not statistically significant.

Conclusion: The study found that restricted salt intake could significantly reduce systolic and diastolic BP. Further, multi-center RCTs for longer durations across different stages of CKD could effectively assess the effects of restricted sodium intake on vital parameters. Such study designs could also help clinicians identify the optimal intake of dietary sodium to achieve better renal and cardio vascular outcomes.

Keywords: Chronic kidney disease; Meta-analysis; Sodium restricted diet


Non-Communicable Diseases (NCDs) have replaced communicable diseases and is the most common form of morbidity and eventually mortality across the globe [1,2]. Among the NCDs, the burden of CKD is on a rise due to the multitude of risk factors associated with the disease. Evidence from literature suggests that CKD affects about 10-16% of the adults across the globe [3]. The burden of CKD is well established in developed countries but recent studies suggest that CKD burden may be even higher in developing countries [4]. This increase may be related to the increase in rates of hypertension and diabetes [3]. Much of the morbidity and mortality associated with diabetes and hypertension are attributable to kidney disease and its complications. The demographic transition driving this rise is expected to occur predominantly in developing countries and will further continue to challenge the economic capacity of these countries to provide RRT to the already increasing number of people with ESKD [5].

The global action plan for the prevention and control of NCDs (2013-20) outlined an approach to reduce the mortality from four major categories of NCDs namely - cancer, cardiovascular disease, chronic respiratory disease and diabetes by 25% by the year 2025 [6]. The Global Burden Of Disease (GBD) 2015 study estimated that 1.2 million deaths, 19 million Disability-Adjusted Life Years (DALYs) and 18 million years of life lost from CVDs were directly attributed to reduced GFR [7,8]. It also estimated that in 2015, 1.2 million people died from renal failure, an increase of 32% since 2005 [8]. In 2010, an estimated 2.3-7.1 million people with ESKD died without access to RRT [9]. It is also possible that limited availability of epidemiological data and poor awareness about the consequences of CKD might seriously underestimate the burden of CKD. This might be a severe complication in regions with inadequate public health systems.

Initiation of RRT or renal transplants for people with ESKD possess serious economic burden. High-income countries typically spend 2-3% of their health-care budget on the treatment of ESKD even though less than 0.3% of the total population receive these treatments [10]. In 2010, 2.62 million people received dialysis therapy worldwide and this number is expected to double by 2030 [9]. However, if risk factors related to renal function is identified early, deterioration of renal function can be slowed down by the means of cost-effective interventions, several of which are available on the WHO’s ‘Best Buys and other recommended interventions for the prevention and control of NCDs’ [6] which also includes reduced dietary sodium intake.

The relation between excess sodium intake with hypertension and kidney disease is well known. In the general population high sodium intake is associated with hypertension and cardio vascular events. It increases the extent of release of albuminuria in CKD patients as well as the general population [11]. RCTs conducted in the past have also shown that reducing sodium intake has significantly reduced systolic BP and diastolic BP [12]. This cost-effective intervention might help renal impaired patients to delay the initiation of RRT. It is imperative that we perform a systematic review of the available literature to understand the effect of the most commonly recommended dietary intervention in the management of CKD - sodium restricted diet.


Search strategy

The present review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [13]. We searched the online databases - PUBMED, Cochrane Kidney and Transplant Specialized Register, Cochrane Library and Google Scholar to 31 December 2020 for RCTs to be included in this meta-analysis. The search strategy was limited to those articles published in English. The following keywords were used as part of the search strategy - chronic kidney disease, CKD, sodium diet, renal disease, renal insufficiency, chronic renal insufficiency, nephropathy, glomerular disease and glomerulonephritis. References of these studies were also screened to further identify potentially relevant studies for the review. The search was carried out from 15th May 2021 till 15th June 2021. Boolean operators such as “OR”, “AND” were used in the search strategy. The protocol was registered with PROSPERO International prospective register of systematic reviews vide registration number CRD42021254921.

Inclusion criteria

We included all RCTs which evaluated the effects of low versus high sodium intake in people with CKD including those with ESKD. The studies included in the meta-analysis should have been published in a peer-reviewed journal. The titles and abstracts of articles from the search strategy were screened and those papers were carefully reviewed before including it in the review using the pre-defined inclusion criteria.

Exclusion criteria

We excluded studies on pregnant women, on children less than 18 years of age, which were followed up for less than 4 weeks, which did not report data on numbers in exposed and un-exposed categories and number of outcomes in the two categories and when it was impossible to extract data from the published results of the study. The articles which were found in languages other than English were also excluded from the meta-analysis.

Interventions (Exposure)

We considered the intervention of restricted sodium diet on patients with CKD including those with ESKD. Accordingly, we included studies which were RCTs measuring the effects of low versus high sodium intake in people with CKD and ESKD. The studies included in the review should compare two or more levels of differing sodium intake and should be followed up for at least 4 weeks.

Outcome measurements

• Change in systolic and diastolic BP

• Change in serum creatinine

• Change in eGFR

• Change in serum urea

Data collection, extraction and analysis

The above mentioned search strategy was used to obtain titles and abstracts of the studies that could potentially be used in our review. The titles and abstracts were screened and those studies that were deemed to be unsuitable for our review were discarded based on the exclusion criteria. Data from the included studies in the review was extracted using the standard extraction forms available from the Cochrane Library. Only those studies which reported relevant outcome measurements were included in the review. In the studies which reported the outcome measures at different time periods, the most recent one was used for the analysis. We then coded and categorized the interventions used in each of the studies selected for the review. Studies with multiple interventions were analyzed for each arm against control and the analysis was performed separately for each arm. Review Manager (RevMan) version 5.3, The Cochrane Collaboration [14] was used to abstract and collect information about the study characteristics, descriptions of the interventions and comparisons, outcome of interest and effects. We assessed quality based on the CHERG adaptation of the GRADE checklist at individual study level [15].

Assessment of heterogeneity

Heterogeneity of the studies considered was assessed using a Chi- Squared test at 5% level of significance. In addition, I² test was also applied. Its values of 25%, 50% and 75% correspond to low, medium and high levels of heterogeneity respectively [16].

Measurement of treatment effect

Inverse variance methods were applied for analysis using random effects models. Continuous scales of outcome measurement were used to assess the effects of the interventions. The outcome measurements in the study were continuous (such as serum creatinine, eGFR, albuminuria, proteinuria, Protein Creatinine Ratio (PCR), Albumin Creatinine Ratio (ACR), blood pressure). In such cases, the Mean Difference (MD) is measured if same scales of measurements were used or the Standardized Mean Difference (SMD) if different scales of measurements were used corresponding to 95% Confidence Interval. In studies reporting measures at different intervals, the scores at the endpoint was used in the meta-analysis. Forest plots were plotted to measure treatment effects and to make inferences.


Systematic review

The search strategy yielded 854 results across PUBMED, Cochrane Kidney and Transplant Specialized Register and Google Scholar. After initial screening for title and abstracts 164 records were screened for including in the review. These full-text articles were assessed for inclusion for qualitative synthesis. Further, 157 records were excluded because of Non-RCTs, text not in English and wrong intervention. The remaining 7 studies (8 reports) with 465 participants were enrolled in the low-sodium versus standard diet which was used for performing meta-analysis. Figure 1 presents the flow chart of the study selection process for the meta-analysis.