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Recommendations Summary

CKD: Electrolytes: Sodium (2020)

Click here to see the explanation of recommendation ratings (Strong, Fair, Weak, Consensus, Insufficient Evidence) and labels (Imperative or Conditional). To see more detail on the evidence from which the following recommendations were drawn, use the hyperlinks in the Supporting Evidence Section below.


  • Recommendation(s)

    CKD: Sodium Intake and Blood Pressure, CKD 3-5, Non-Dialyzed

    In adults with CKD 3-5 not on dialysis, we recommend limiting sodium intake to less than 100 mmol/day (or <2.3 g/day) to reduce blood pressure and improve volume control (1B).

    Rating: Strong
    Imperative

    CKD: Sodium Intake and Blood Pressure, CKD 5D and Post-Transplant

    In adults with CKD 5D or posttransplantation, we recommend limiting sodium intake to less than 100 mmol/day (or <2.3 g/day) to reduce blood pressure and improve volume control (1C).

    Rating: Fair
    Imperative

    CKD: Sodium Intake and Proteinuria

    In adults with CKD 3-5,  we suggest limiting sodium intake to less than 100 mmol/day (or <2.3 g/day) to reduce proteinuria synergistically with available pharmacological intervention (2A).

    Rating: Fair
    Conditional

    CKD: Sodium Intake and Dry Body Weight

    In adults with CKD 3-5D, we suggest reduced dietary sodium intake as an adjunctive lifestyle modification strategy to achieve better volume control and a more desirable body weight (2B).

    Rating: Fair
    Conditional

    • Risks/Harms of Implementing This Recommendation

      A nutrition prescription that is too high or too low in sodium may result in adverse outcomes.

    • Conditions of Application

      Implementation considerations

      • Achieving a reduced sodium intake in CKD is recommended, however can be particularly challenging to achieve (Meuleman et al 2018). This is a result of the need to navigate a complex interplay between individual food choice and food supply, together with a range of other dietary recommendations that come with CKD. As sodium is consumed largely from processed foods, the World Health Organization (WHO) has initiatives for reducing sodium content in manufactured foods among the top priorities to combat non-communicable diseases (McMahon et al 2012). Consuming a low sodium diet generally requires education and skill development (cooking, label reading) and explicit choice to consume a low sodium diet. Therefore, a concerted and multi-faceted intervention strategy is required to support achieving this intake in clinical practice. This includes targeting individual behavior change for dietary choices, together with a wider public health strategy to reduce availability of sodium in the food supply (McMahon et al 2012).
      • The interventions undertaken in clinical trials of sodium reduction have limited applicability when translating into practice. Many trials to date have used sodium supplementation or provided foods to enhance adherence in short-term effectiveness studies (McMahon et al 2012). Investigations of efficacy and behavioral interventions to adopt low sodium intakes in real-life settings are limited in the literature. Of those that exist, the evidence is either short term (< 6 months) or demonstrate that achieving a reduced sodium intake is only apparent whilst receiving active intervention (Meuleman et al 2017). The challenge for the future is to develop an evidence-base to inform successful strategies to support long-term adherence to dietary sodium reduction.
      • Issues with sodium intake assessment: Measuring sodium intake and thereby accurately evaluating adherence to recommendations is extremely challenging in practice. Sodium intake can be measured in objective (urine collection over 24 hours or spot sample) and self-report (dietary recall) or a combination of methods. Urinary sodium excretion as a surrogate measure of intake assumes 1) a stable intake reflected in a single 24hour collection, 2) sodium excretion is a direct reflection of intake. It is this latter assumption which has been recently challenged by Titze and colleagues, who have identified a sodium storage pool in the skin and a wide disparity between sodium intake and excretion day to day (Titze et al 2014). Increasing the number of 24-hour urinary collections may improve the accuracy to partially overcome these concerns, however it is not practical in clinical practice. Self-reported dietary assessment methods are prone to reporting bias and can be time consuming to collect and require technical expertise in the analysis. A panel of methods is therefore recommended, as no one method is ideal to adequately assess adherence (McMahon et al 2012).
      • Sodium relative to potassium intake: Recent observational evidence suggests that the ratio of sodium-to-potassium intake may be as important, if not more important than lower sodium intake alone in CKD (He et al 2016). This is the premise of the DASH-Sodium trial, and has demonstrated benefits in the general population, with sodium reduction providing additive benefit in BP reduction to the DASH diet (Juraschek et al 2017). In hypertensive adults, post-hoc analysis of clinical trials indicate sodium-to-potassium ratio may be more effective in lowering BP than lowering sodium or increasing potassium as single interventions (Aaron et al 2013). However, there are unknown safety aspects in CKD, particularly with the risk of hyperkalemia. Investigating the relative benefit of sodium reduction compared to potassium intake is beyond the scope of the current guidelines however warrants further research. Evidence for Potassium recommendations is addressed within these guidelines.
      • Currently, there is too much uncertainty in the evidence to advice on the effectiveness of sodium restriction based on specific thersholds of proteinuria. However, this intervention appears to be effective over a large range of proteinuria.

    • Potential Costs Associated with Application

      There are no obvious costs associated with the implementation of these recommendations. 

    • Recommendation Narrative

      Sodium is an extracellular cation responsible for fluid homeostasis in the body (Geerling et al 2008). Normovolemia is maintained through the action of the renin-angiotensin aldosterone system (RAAS). This system acts to adjust the quantity of sodium excreted by the body, and thereby ECF volume and arterial BP. Excess sodium intake is excreted in the urine and serum levels are tightly controlled. requiring normal kidney and blood vessel function (Schweda et al 2015).  However, this system may be compromised with excessive sodium intake, and/or inadequate excretion, which may occur with chronic kidney disease.

      Chronic high sodium intake may impact on a number of physiological functions relating to the vasculature, heart, kidneys and sympathetic nervous system (Kotchen et al 2013).  Excessive sodium intake is thought to exert toxic effects on blood vessels through mediating factors such as oxidative stress, inflammation and endothelial dysfunction (Dinh et al 2014). Of particular interest in CKD is the role of sodium reduction in improving the pharmacological effect of antihypertensive medication thereby controlling hypertension.

      In the general population, short-term intervention studies show significant reductions in BP (hypertensive subgroup, reductions of 5.8 mmHg systolic BP [SBP] and 2.82 mmHg diastolic BP [DBP]) with 100mmol/d reduction in sodium intake (He, et al. 2013). Indications from a small number of long-term studies (>6 months) suggest a benefit for CV-morbidity and mortality, although the studies were underpowered to adequately examine these outcomes (Adler et al 2014). The following will explore the evidence within CKD.

      Overall, the evidence for reducing sodium intake comes from randomized controlled trials of short duration and typically small sample size. As a result, there is a focus on clinical markers such as BP, inflammation, body weight, fluid and proteinuria. There is limited evaluation of hard outcomes, which thereby rely upon observational evidence. In addition, the certainty of evidence for sodium reduction is limited by imprecision and risk of bias, particularly selection, attribution and performance bias.

      Five randomised controlled trials (1 parallel (de Brito-Ashurst et al 2013) and 4 cross-over studies (McMahon et al 2013, Slagman et al 2011, Vogt et al 2008, Konishi et al 2001) examined the effects of reduced dietary sodium intake on blood pressure and a range of outcomes in CKD (Stage 2 to 5, non-dialysis). The cross-over studies utilised supplemental sodium (McMahon et al 2013, Slagman et al 2011, Vogt et al 2008) or provided meals (Konishi  et al  2011) on the background of a low sodium diet to generate consistent intake in the high (180 mmol to 200mmol/d, with ~100-120mmol/d supplemented) vs low sodium intake group (placebo, total 50 to 0 mmol sodium per day). The parallel RCT was the longest study duration (six months) conducted in a sample of Bangladeshi immigrants in the UK (n=48) (deBrito-Ashurst et al 2013). Participants were randomised to a tailored intervention including cooking classes modifying traditional cultural recipes together with regular telephone calls with a dietitian. From a baseline sodium intake of approximately 260mmol, the intervention group achieved 138mmol/day (a reduction of over 120mmol), whilst usual care stayed largely stable (to 247 mmol/d). Correspondingly mean SBP reduction of ~7mmHg and 1mmHg increase in the intervention and control group, respectively. Diastolic blood pressure (DBP) reduced by 5mmHg and 2mmHg the intervention and control group, respectively (de Brito-Ashurst et al 2013).

      Two more recent studies build upon this evidence base and include a parallel (Meuleman et al 2017) and a cross-over trial (Saran et al 2017). Meuleman and colleagues conducted a 3 month open-label RCT, n= 138 adults with CKD, hypertension, and high urinary sodium excretion (≥120 mmol/day). The intervention focused on self-management advice to reduce sodium (goal <100mmol/day) and blood pressure monitoring, or usual care. The intervention led to significant decreases in 24-hour urinary sodium excretion and blood pressure at 3 months, as well as in the secondary outcomes of proteinuria and body weight. However, 3 months after the cessation of the 3 month coaching period, the sodium intake was no longer different between the groups, however clinic BP remained significantly lower at 6 months. In the most recent cross-over trial, Saran et al evaluated the effect of sodium restriction <2g/day vs usual diet for 4 weeks (with a 2 week washout in-between) in Stage3 and 4 CKD. This study improved upon previous cross-over trials as it used dietary counselling, rather than sodium supplementation, to achieve the difference between usual and sodium restricted intakes.

      Four trials were conducted in the maintenance dialysis population. One RCT in peritoneal dialysis (PD) (Fine et al 1997), and two RCTs in maintenance hemodialysis (MHD) (Liang et al 2013, Telini et al  2014) and one non-controlled trial in both PD and MHD (Magden et al 2013). In the single study undertaken in MHD, there was no significant reduction in BP (Telini 2014). The difference with this study, compared to all others in dialysis, is that dietary prescription (rather than supplemental sodium) was used to achieve a modest reduction of intake (goal 34 mmol/d lower than usual intake). This compares to the other interventions in maintenance dialysis using sodium supplementation, which achieved a much larger gradient of difference in sodium intake between low and high intake groups (100mmol.d or 2.3g sodium difference). 

      One RCT was undertaken in patients post kidney transplantation (Keven et al 2006). This was a parallel RCT of a 12-week intervention that included counselling by a dietitian for a target intake of 80-100mmol/day compared with usual care. This trial demonstrated a significant reduction in sodium intake in the intervention group (from 190±75 mmol/d to 106±48 mmol/d) through dietary counselling, with no significant change in the usual care group (191±117 mmol/d to 237±113 mmol/d)  

      In the vast majority of trials, the target sodium restriction was 80-100 mmol/day (or 2-2.3g/day). However, there was a lack of consensus as to what constitutes a high sodium intake, which was either based on usual intake, or providing supplemental sodium to ensure a consistently high sodium intake, around 200mmol or 4g sodium per day. 

      Mortality, CKD Progression and Cardiovascular Events
      There is insufficient evidence to make a statement on reduced sodium intake and kidney disease progression,  mortality and cardiovascular events. The evidence for clinical endpoints is derived from observational studies as there were no RCTs in sodium reduction in CKD that reported CKD progression cardiovascular events, mortality outcomes. This is attributable to the small sample sizes and the longest trial duration only six months (de Brito-Ashurst et al 2013).

      The post-hoc analysis of two observational cohort studies showed mixed results investigating the association between sodium intake (measured by dietary recall) and subsequent mortality in hemodialysis (McMahon et al 2015) and peritoneal dialysis (PD) patients (Dong et al 2010). The retrospective cohort study in 303 PD patients in Japan indicated that low sodium intake was significantly associated with higher overall and cardiovascular mortality. However, this study was open to indication bias as sodium intake was also associated with higher lean body mass, younger age and higher BMI. In contrast, in a post-hoc analysis of a prospective cohort of 1770 MHD patients, McCausland et al found higher dietary sodium intake associated with increased mortality (Mc Causland et al 2012).

      More consistent results were demonstrated from a large high-quality prospective cohort (CRIC study) of predialysis Stage 2-4, using urinary sodium excretion. In He et al, 24-hour urinary sodium excretion was associated with greater all-cause mortality and CKD progression (defined as incident ESRD or halving of eGFR from baseline) (He et al 2016).  Sodium excretion was also associated with composite CVD (heart failure, myocardial infarction, stroke) (Mills et al 2016).

      Blood Pressure
      Overall, sodium reduction probably reduces BP in kidney disease (moderate certainty evidence). This evidence review included 9 small (n=20 to n=52) randomized clinical trials (6 were cross-over trials) of short duration (1 week to 6 months), evaluating the effect on reducing sodium intake (typically to a level of <2g or 90mmol/d) on BP. In fact, lower sodium intake significantly decreased systolic BP in all but one study (Rodrigues et al 2014),  which reduced intake by only 34mmol/d, compared with >90 mmol/d from the other trials. However, the certainty of evidence was limited by risk of bias, particularly risk of selection, attribution and performance bias. When evaluating the evidence across stages of CKD, the vast amount of evidence exists in pre-dialysis CKD, however the BP benefits were also apparent in trials in dialysis (Fine et al 1997, Rodrigues et al 2014, Magden et al 2013, Koomans et al 1985) and transplantation populations (Keven et al 2006).

      Although this review was unable to derive a summary estimate, a Cochrane review on this topic published in 2015 showed dietary sodium reduction (MD -105.9, 95% CI -119.2 to -92.5mmol/day) resulted in significant reduction in systolic BP (MD -8.76, 95% CI -11.35 to -3.80 mm Hg). These short-term studies showing clinically meaningful systolic BP reductions ranging from 2-12mmHg systolic BP and 1-8mmHg diastolic BP in trials one week to six months in duration (McMahon et al 2015.

      Inflammatory Markers
      Sodium reduction may make little to no difference to inflammation (low certainty evidence). Two RCTs, a parallel RCT in MHD (Rodrigues et al 2014),  and a crossover in Stage 3 and 4 (McMahon et al 2013),  investigated the impact of sodium restriction on inflammation, measured by CRP, IL-6, TNF-alpha. In the Telini study there was a significant reduction in all inflammatory markers within the intervention group, however not reported between group differences (and no difference within control group) (Rodrigues et al 2014). The single crossover study in Stage 3-4 showed no difference in inflammation comparing high and low sodium intake (McMahon et al 2013).

      Body Weight and Fluid
      Sodium restriction may slightly reduce body weight and total body fluid in non-dialysis CKD (low certainty evidence). However, it is uncertain whether sodium restriction reduces body weight and body water in dialysis. The evidence from non-dialysis CKD comes from two randomized-crossover trials, one using sodium supplementation to compare intake of 60-80mmol/d to 180-200mmol/d for 2 weeks (McMahon et al 2013) together with a more recent investigation by Saran et al evaluating the effect of sodium restriction <2g/day vs usual diet for 4 weeks (with a 2 week washout in-between). Both trials demonstrated a reduction in extracellular volume. Furthermore in maintenance dialysis, two RCTS demonstrated no significant difference in body weight with salt restriction in peritoneal (Fine et al 1997) or both hemodialysis and peritoneal dialysis. In one non-randomaize study in hemodialysis, the group advised to restrict sodium intake (<3 g /day) and fluid (<1 L/d) demonstrated within group decrease in interdialytic fluid gain, but there was no change in the control group, and between group difference was not significant (Liang et al 2013).

      Kidney Function (including Proteinuria)
      Restriction of sodium intake may slightly reduce kidney function markers of creatinine clearance (Konishi et al 2001, Slagman et al 2011, Vogt et al 2008, Koomans et al 1985) and eGFR (Campbell et al 2014) demonstrated in short-term cross-over trials in the stage 1-5 non-dialysis population (low certainty evidence). In the single parallel RCT over 6 months of sodium restriction, deBrito-Ashurst found no difference in eGFR (de Brito-Ashurst et al 2013). The inconsistency in results may be due to the short-term cross-over trials demonstrating acute hyper filtration response to low sodium intake, compared with the longer-term parallel trial, reflecting a more clinically stable circumstance.

      Restriction of sodium intake may reduce proteinuria as demonstrated in 3 randomized cross-over trials (McMahon et al 2013, Slagman et al 2011, Vogt et al 2008, Campbell et al 2014). This evidence is supported by further parallel RCTs and observational studies. Meuleman et al demonstrated a reduction in proteinuria over 3 months self-management intervention using a sodium intake <100mmol/d (Meuleman et al 2017). In addition, in a post-hoc analyses of clinical trials (REIN I & II) in proteinuric patients with established CKD have demonstrated participants consuming a higher sodium diet was associated with an increased risk of progressing to ESKD compared to a lower sodium diet <100mmol/d (Vegter et al 2012).

    • Recommendation Strength Rationale

      The evidence supporting the recommendation on sodium and proteinuria in non-dialyzed patients is based on Grade I /Grade A evidence, while the remaining recommendations for sodium for non-dialzyed patients are based on Grade II/Grade B evidence. The recommendation for sodium and blood pressure for patients with CKD on MHD and post-transplant was based on Grade III/Grade C evidence. 

    • Minority Opinions

      Consensus reached.