CKD: Electrolytes: Acid Load (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.
CKD: Dietary Management of Net Acid Production (NEAP)
In adults with CKD 1-4, we suggest reducing net acid production (NEAP) through increased dietary intake of fruits and vegetables (2C) in order to reduce the rate of decline of residual kidney function.
CKD: Bicarbonate Supplementation
In adults with CKD 3-5D, we recommend reducing net acid production (NEAP) through increased bicarbonate or a citric acid/sodium citrate solution supplementation (1C) in order to reduce the rate of decline of residual kidney function.
CKD: Bicarbonate Maintenance
In adults with CKD 3-5D, it is reasonable to maintain serum bicarbonate levels at 24-26 mmol/L (OPINION).
Risks/Harms of Implementing This Recommendation
In CKD 5 maintenance hemodialysis (MHD) patients, higher bicarbonate in the dialysate bath is associated with increased mortality in epidemiological studies (Yamamoto et al 2015). In an analysis of the DOPPS data, it was reported MHD patients with either very low bicarbonate (< 17) or very high predialysis bicarbonate (>27) concentrations are at the greatest mortality risk (Bommer et al 2004).
Conditions of Application
In CKD 5 MHD patients, higher bicarbonate in the dialysate bath is associated with increased mortality in epidemiological studies (Yamamoto et al 2015). In an analysis of the DOPPS data, it was reported MHD patients with either very low bicarbonate (< 17) or very high predialysis bicarbonate (>27) concentrations are at the greatest mortality risk (Bommer et al 2004). Paradigms that may apply to patients with residual renal function or those undergoing continuous therapy, such as peritoneal dialysis, do not directly apply to hemodialysis patients who are experiencing large changes in acid base equilibrium rapidly and/or discontinuously. Higher bicarbonate concentration in hemodialysis patients may also be reflective of lower protein intake.
Research on this topic is complicated by the fact that the effect of acidosis differs with the level of residual kidney function. With advanced CKD, net acid load has a higher potential to contribute to loss of kidney function. (Grade A evidence)
Dietary intervention is more complex, since the effects of specific amino acids or other dietary constituents on both renal outcomes as well as vascular and bone pathophysiology (Calcium/Phosphorous) may play a role that is independent from their effect on acid base physiology.
- Acid load is a consequence of protein load and is inversely associated with potassium intake. The estimation of net acid intake is (NEAP (mEq/d) = -10.2 + 54.5 (protein [g/d]/potassium [mEq/d]). NEAP can be reduced by administration of sodium bicarbonate or sodium or potassium citrate or by reduction in dietary acid content by changing the dietary pattern to increase fruits and vegetables. The latter can be accomplished by reduction in dietary protein intake and changing its composition. Low protein intake may have the added benefit of slowing the rate of progression of kidney disease through other mechanisms (See Protein Section). In the MDRD study, patients randomized to low protein intake exhibited a significant increase in serum bicarbonate (Gennari et al 2006), so that there is an interaction between intake of protein and net acid. Separating the effect of reduction in acid load and the effect of change in dietary protein amount and composition on outcomes is challenging.
- When increasing fruits and vegetables intake to correct acid load please use caution and monitor potassium levels.
Monitoring and Evaluation
Clinical trials have demonstrated compliance with expected changes in acid base status as evaluated by measurement of serum bicarbonate:
- Consuming fruit and vegetable in the amount that could reduce dietary acid by 50% generally had positive effects on acid-base biomarkers (Goraya et al 2012, 2013, 2014). Fruit and vegetable increased plasma total CO2 (though not significant in one study) (Goraya et al 2012) and decreased potential renal acid load and 8h NAE. Except for Goraya et al, (0.5 mEq/kg/day) (Goraya et al 2012), oral bicarbonate supplements also had positive effects on acid-base biomarkers by increasing plasma total CO2 or bicarbonate levels and decreasing potential renal acid load and 8h NAE in six studies with different supplement combinations and dosages.
- No hyperkalemia events were noted in the studies of Goraya et al. who provided a diet rich in fruits and vegetables to patients with advanced CKD. However, we note that inclusion criteria in those studies considered patients at low hyperkalemia risk not consuming RASi. While no studies have formally evaluated the contribution of dietary potassium to hyperkalemia risk in these patients, we recommend caution if a fruit and vegetable rich diets is to be recommended to control metabolic acidosis. A close monitoring of serum/plasma potassium levels is encouraged, and fruit/vegetable consumption should be temporarily limited if the patient is considered at risk of hyperkalemia. Monitoring of circulating potassium is specially recommended in patients with CKD stage 4 or more, including those on dialysis, as this is the kidney function range where inabilities to compensate dietary potassium occur.
Potential Costs Associated with Application
There are no obvious costs associated with this recommendation.
Acid base homeostasis is maintained by urinary acidification using titratable anions, such as phosphate, to trap proteins, and trapping ammonia that is generated as ammonium in an acid urine. As kidney function declines, the net acidification requirement by residual nephrons increases. This is accomplished by increasing ammonia production per residual nephron and requires delivery of glutamine to the residual nephrons. The increased per nephron need for increased acidification and ammonia genesis is in part endothelin controlled and may increase injury to residual nephrons. Acid retention also would have the potential to promote muscle wasting as part of the homeostatic processes of normalizing acid base status. Metabolic acidosis increases skeletal muscle proteolysis by a ubiquitin proteasome pathway that degrades actin potentially having adverse nutritional impact on the patient accompanied by an increase in protein catabolic rate.
Eleven studies examined the association between dietary acid load/oral bicarbonate supplements on health outcomes in the CKD population. Of the included studies, there were four RCTs (Goraya et al 2013, 2014, de Brito-Ashurst et al 2009; Szeto et al 2003), one NRCT (Goraya et al 2012), three non-controlled studies (Kooman et al 1997, Movilli et al 1998, Verove et al 2002), two prospective cohort studies (Banerjee et al 2015, Scialla et al 2012), and one retrospective cohort study (Kanda et al 2014).
CKD Progression: Effect of Reducing Net Acid Production
Studies aimed at evaluating the effect of reduction in net acid production (NEAP) have been two fold; either directly reducing NEAP by administration of sodium bicarbonate, or by dietary alteration using fruits and vegetables, which both decrease NEAP and alter the composition and quantity of dietary protein partially confounding the effect of reduction of NEAP alone. In adults with CKD, four RCTs (Goraya et al 2013, 2014, de Brito-Ashurst et al 2009; Szeto et al 2003), one non-RCT (Goraya et al 2012), two non-controlled studies (Movilli et al 1998, Verove et al 2002), two prospective cohort studies (Banerjee et al 2015, Scialla et al 2012), and one retrospective cohort study (Kanda et al 2014). examined the effects of dietary fruit and vegetable or oral bicarbonate supplements on CKD progression. In patients with CKD stages 2-4 (20-65 mL/min per 1.73 m2) higher quartiles of net endogenous acid production (NEAP) were associated with greater I 125iothalamate glomerular filtration rate (iGFR) decline (p-trend=0.02) (Scialla et al 2012). In CKD 3-5 (≤ 60 mL/min per 1.73 m2) higher NEAP is associated with CKD progression (p<0.05 for all quartile groups) (Kanda et al 2014). In CKD stages 3-4 (≥15 or <60 mL/min per 1.73 m2) compared to lowest dietary acid load tertile, highest dietary acid load had greater relative hazard of ESRD (p=0.05) (Banerjee et al 2015).
Studies reducing NEAP by the use of administration of oral sodium bicarbonate are not confounded by alteration in dietary protein composition and easier to study in randomized controlled prospective manners. In studies involving patients with CKD 4-5, the oral sodium bicarbonate group had significant greater creatinine clearance after 18 and 24 months (p<0.05). Rapid CKD progression (creatine clearance loss of >3ml/min per 1.73m2/yr) was lower in the oral sodium bicarbonate group (RR: 0.15; 95% CI: 0.06-0.40). Development of ESRD was lower in the oral sodium bicarbonate group (RR: 0.13; 95% CI: 0.04-0.40) (de Brit-Ashurst et al 2009). In another study of CKD 4-5; not on dialysis, there was no significant difference in creatinine clearance between before and after intervention (p>0.05) (Verove et al 2002). In patients with less impaired renal function at baseline (CKD 3), there was a reduction in eGFR in all groups, however, at 3 years, lesser reduction in eGFR was observed with HCO3 group or fruits and vegetables than usual care group (Goraya et al 2014).
In a study by Goraya et al, 2013 in patients with CKD 4 using either fruits and vegetables or NaHCO3 as the intervention, plasma creatinine levels were comparable between the subjects treated either with HCO3 or fruits and vegetables at baseline and 1-year follow-up (p=0.99, 0.49, respectively), eGFR were comparable between the two groups at baseline and 1-year follow-up (p=0.84, 0.32, respectively) (Goraya et al 2013). This study does not isolate the effects of alteration in dietary composition and NEAP sufficiently to establish which intervention is associated with any biological change observed.
The outcome of studies in patients with CKD1-2 are less clear and the outcomes not as definitive. This may in part be due to the fact that the per nephron stress of maintaining acid/base balance is reduced, either decreasing the renal risk of acidification below a critical threshold, or by reducing the power necessary to measure an effect. Additionally studies that alter NEAP by changing dietary composition are confounded by other variables, such as amino acid load and quality. One of the outcome variables measured was urinary albumin excretion.
Net urine albumin excretion was not different among the three groups in CKD 1 patients (p>0.05). However, in CKD 2 patients, fruits and vegetables had greater decrease in net urine albumin excretion than both HCO3 and control (p<0.05) and HCO3 group had greater decrease in net urine albumin excretion than control (p<0.05) (Goraya et al 2012). It should be noted that a change in diet towards higher intake of fruit and vegetables is a different and more complex intervention than change in NEAP since the amino acid load and composition is changed. This may affect urinary protein loss and have an effect on progression that is independent of NEAP if the patient population has significant proteinuria.
The effects of oral bicarbonate supplements on hospitalization in CKD patients were mixed, though evidence is limited. In adults with chronic kidney disease, two RCTs (de Brito-Ashurst et al 2009, Szeto et al 2003) examined the effects of oral bicarbonate supplements on hospitalization. Among CKD Stage 5 patient; peritoneal dialysis, compared with placebo group, intervention group had lower hospital admission (trend) and hospital length of stay (p=0.07 and 0.02, respectively) (Szeto et al 2013). In CKD Stages 4-5; pre-dialysis, there was no significance difference in hospitalization for heart failure between the two groups (p=N/A) (de Brito-Ashurst et al 2009).
In CKD 3-5 patients including ones on maintenance dialysis, oral bicarbonate supplements improved nutritional status (e.g., SGA scores, nPCR, albumin, and prealbumin) in most studies. Oral bicarbonate supplements increased overall SGA scores (Szeto et al 2003- 2.7 g/day) and lowered nPNA (nPCR) (de Brito-Ashurst -~1800 mg/day) (de Brito-Ashurst). Except for Kooman et al, (dialysate bicarbonate and oral sodium bicarbonate (1500-3000 mg) if pre-dialytic bicarbonate did not reach desired level), the other three studies observed positive effects of oral bicarbonate supplements on serum albumin or prealbumin levels (de Brito-Ashurst -~1800 mg/day; Movilli et al, - mean dose 2.7±0.94 g/day; 1–4 g/day; Verove et al, 2002 – mean dose 4.5±1.5g/d. Oral bicarbonate supplements also had no effects on TSF measurements (Kooman et al 1997). de Brito-Ashurst et al, (~1800 mg/day) noted significant increases in mid arm muscle circumference (MAMC) measurements with oral sodium bicarbonate, while Kooman et al, 1997 did not.
Two RCTs (de Brito-Ashurst et al 2009, Szeto et al 2003) and three non-controlled studies (Kooman et al 1997, Movilli et al 1998, Verove et al 2002) examined the effects of oral bicarbonate supplements on nutritional status in adults with CKD. In CKD Stage 5; peritoneal dialysis, the oral bicarbonate group had higher overall SGA scores starting at 24 weeks (p-value <0.0003) (Szeto et al 2013). In CKD 4-5; pre-dialysis, the oral sodium bicarbonate group had significant lower nPNA (nPCR) at 12 and 24 months (p<0.05) and the oral sodium bicarbonate group had significant higher serum albumin at 12 and 24 months (p<0.05) (de Brito-Ashurst et al 2009).
In contrast, in a group of CKD 5; hemodialysis patients, there was no significant difference in serum albumin among time points (p>0.05) (Kooman et al 1997). In CKD 5; hemodialysis, oral sodium bicarbonate increased serum albumin level (p=0.01) (Movilli et al 1998).
It should also be noted that high dialysate bicarbonate concentrations are associated with increased mortality in observational studies (Yamamoto et al 2015). Among CKD 4-5; pre-dialysis, oral sodium bicarbonate increased both serum albumin and prealbumin levels between before and after intervention (p<0.05) (Verove et al 2002). Among CKD 1-2 compared to control and HCO3, fruit and vegetable group had significantly greater decrease in body weight at the end of the intervention for both individuals with CKD 1-2 (p<0.05 for both). No difference between HCO3 and control (Goraya et al 2012). Thus there does not appear to be a significant effect of reduction in NEAP on nutritional status in patients with CKD 1-2. In CKD 4 compared to HCO3 group, FV group had lower weight at 1-year follow up (p<0.01) – baseline weight did not differ between the two groups (p=0.24) (Goraya et al 2013). In CKD 3, fruits and vegetables had greater net body weight loss than both HCO3 and control (p<0.05) and control group had greater net body weight loss than HCO3 group (p<0.05) (Goraya et al 2014).
Recommendation Strength Rationale
The evidence supporting the recommendations on dietary management of NEAP with fruits and vegetables and bicarbonate supplementation is based on Grade III /Grade C evidence. The recommendation regarding barcarbonate maintenance based on Consensus/expert opinion.
- Risks/Harms of Implementing This Recommendation
The recommendations were created from the evidence analysis on the following questions. To see detail of the evidence analysis, click the blue hyperlinks below (recommendations rated consensus will not have supporting evidence linked).
What is the effect of acid-base interventions on hospitalizations and mortality in adults with CKD 1-5D and post-transplant?
What is the effect of acid-base interventions on blood pressure in adults with CKD 1-5D and post-transplant?
What is the effect of acid-base interventions or NEAP/acid load levels on CKD progression in adults with CKD 1-5D and post-transplant?
What is the effect of acid-base interventions on acid-base levels in adults with CKD 1-5D and post-transplant?
What is the effect of acid-base interventions on fluid status in adults with CKD 1-5D and post-transplant?
What is the effect of acid-base interventions on body weight/BMI in adults with CKD 1-5D and post-transplant?
What is the effect of acid-base interventions on MAMC/TSF in adults with CKD 1-5D and post-transplant?
What is the effect of acid-base interventions on CRP levels in adults with CKD 1-5D and post-transplant?
What is the effect of acid-base interventions on nutritional status indicators in adults with CKD 1-5D and post-transplant?
What is the effect of acid-base interventions on nPNA in adults with CKD 1-5D and post-transplant?
What is the effect of acid-base interventions on caloric and protein intakes in adults with CKD 1-5D and post-transplant?
de Brito-Ashurst I, Varagunam M, Raftery M, Yaqoob M. Bicarbonate Supplementation Slows Progression of CKD and Improves Nutritional Status. Journal of the American Society of Nephrology 2009; 20:2075-84
Banerjee T, Crews D, Wesson D, Tilea A, Saran R, Ríos-Burrows N, Williams D, Powe N. High Dietary Acid Load Predicts ESRD among Adults with CKD. Journal of the American Society of Nephrology : JASN 2015; 26:1693-700
Kanda E, Ai M, Kuriyama R, Yoshida M, Shiigai T. Dietary acid intake and kidney disease progression in the elderly. American Journal of Nephrology 2014; 39:145-52
Scialla J, Appel L, Astor B, Miller E, Beddhu S, Woodward M, Parekh R, Anderson C. Net endogenous acid production is associated with a faster decline in GFR in African Americans. Kidney International 2012; 82:106-12
Goraya N, Simoni J, Jo C,Wesson D. Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy. Kidney International 2012; 81:86-93
Goraya N, Simoni J, Jo C, Wesson D. A comparison of treating metabolic acidosis in CKD stage 4 hypertensive kidney disease with fruits and vegetables or sodium bicarbonate. Clinical Journal of the American Society of Nephrology : CJASN 2013; 8:371-81
Goraya N, Simoni J, Jo C, Wesson D. Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate. Kidney International 2014; 86:1031-8
Kooman J, Deutz N, Zijlmans P, van den Wall Bake A, Gerlag P, van Hooff J , Leunissen K. The influence of bicarbonate supplementation on plasma levels of branched-chain amino acids in haemodialysis patients with metabolic acidosis. Nephrology, Dialysis, Transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 1997; 12:2397-401
Movilli E, Zani R, Carli O, Sangalli L, Pola A, Camerini C, Cancarini G, Scolari F, Feller P, Maiorca R. Correction of metabolic acidosis increases serum albumin concentrations and decreases kinetically evaluated protein intake in haemodialysis patients: a prospective study. Nephrology, Dialysis, Transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 1998; 13:1719-22
Verove C, Maisonneuve N, El Azouzi A, Boldron A, Azar R. Effect of the correction of metabolic acidosis on nutritional status in elderly patients with chronic renal failure.. Journal of Renal Nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation 2002; 12:224-8
Szeto C, Wong T, Chow K, Leung C, Li P. Oral Sodium Bicarbonate for the Treatment of Metabolic Acidosis in Peritoneal Dialysis Patients: A Randomized Placebo-Control Trial. Journal of the American Society of Nephrology 2003; 14:2119-2126
References not graded in Academy of Nutrition and Dietetics Evidence Analysis Process
Bommer J, Locatelli F, Satayathum S, et al. Association of predialysis serum bicarbonate levels with risk of mortality and hospitalization in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Amer J Kidney Dis. 2004;44(4):661-71. PMID: 15384017
Gennari FJ, Hood VL, Greene T, Wang X, Levey AS. Effect of dietary protein intake on serum total CO2 concentration in chronic kidney disease: Modification of Diet in Renal Disease study findings. Clin J Am Soc Nephrol. 2006;1(1):52-7. PMID: 17699190
Yamamoto T, Shoji S, Yamakawa T, et al. Predialysis and Postdialysis pH and Bicarbonate and Risk of All-Cause and Cardiovascular Mortality in Long-term Hemodialysis Patients. Am J Kidney Dis. 2015;66(3):469-78. PMID: 26015276