Malnutrition is a common occurrence in CKD patients. The causes are multi-factorial, but poor dietary intake, inflammation, and metabolic acidosis are frequently implicated as primary causes. Although poor dietary intake and inflammation are difficult to correct, metabolic acidosis may have a clear intervention that can result in improved nutritional status.
Metabolic acidosis for the purposes of this article is defined as a serum bicarbonate level of 22 mM or less. Metabolic acidosis has been associated with increased whole body protein degradation, bone disease, muscle catabolism, oxidation of branched-chain amino acids, and increased risk of death in CKD patients. Acidosis begins to occur when kidney function decreases to about less than 20% of normal functioning (Am J Kidney Dis. 2005;33:892-898).
In addition to increased whole body protein degradation and increased muscle catabolism, metabolic acidosis may induce tubulointerstitial injury through endothelin production (Kidney Int. 2010;77:617-623) and has been shown in animal models to induce protein catabolism through the ubiquitin-proteasome pathyway (Proc Natl Acad Sci USA. 1996;93:1967-1971).
Leal et al (J Ren Nutr. 2009;19:178-182) found that in stage 3 and 4 CKD patients, creatinine clearance was significantly higher in patients with serum bicarbonate concentrations greater than 22mM (24.5 vs. 42.9 mL/min). Diet was explored in this study as a potential contributing factor to metabolic acidosis. Thus, acid-producing food consumption, which might result in a lower serum bicarbonate level, was compared between the acidic and non-acidic patients using a validated index, the potential renal acid load or PRAL index. However, the results did not show a significant difference in the PRAL index between the groups indicating that diet was not the cause of reduced serum bicarbonate. Phisitjul et al (Kidney Int. 2010;77:617-623) used sodium citrate to correct metabolic acidosis in non-dialysis CKD patients with hypertensive nephropathy. These patients were on ACE inhibitors to manage BP. At the end of 24 months, the patients on sodium citrate had significantly lower serum creatinine, 8-hour urine endothelin-1 excretion, urine net acid excretion, urine sodium excretion, and higher plasma ionized calcium concentrations. Although, correction of metabolic acidosis did not halt the decline in estimated glomerular filtration rate, it did appear to blunt or slow the rate of decline.
Effects in dialysis patients
Metabolic acidosis is a frequent condition in hemodialysis (HD) and peritoneal dialysis patients. Studies have demonstrated that achieving higher serum bicarbonate and pH levels can have beneficial effects in patients receiving dialysis. In 1998, Movilli et al (Nephrol Dial Transplant. 1998;13:1719-1722) conducted a three-month clinical trial in 12 HD patients with serum bicarbonate concentrations of 20 mmol/L or less for a minimum of three months prior to the study initiation. The patients received an average of 2.7 g/day of sodium bicarbonate during the four-month intervention period. The mean serum bicarbonate concentration increased significantly from 19.3 to 24.4 mmol/L and the serum pH increased significantly from 7.34 to 7.40. Most importantly, serum albumin increased from 3.49 to 3.70 mg/L.
A second, slightly larger, trial was conducted with 29 HD patients to determine the effects of sodium bicarbonate on serum albumin, normalized protein catabolic rate, and high sensitivity C-reactive protein (hsCRP) (J Ren Nutr. 2009;19:172-177). In this trial, patients were treated with a mean of 2.9 g/day of sodium bicarbonate, which resulted in significant increases in both serum bicarbonate and pH levels. Interestingly, the average normalized protein catabolic rate (nPCR) declined significantly after treatment from 1.13 to 1.05. The authors concluded that this may be due to the fact that in an acidic state nPCR is elevated because of increased protein degradation from muscle breakdown verses a high protein intake. Therefore, lower nPCR may be a more accurate reflection of dietary protein intake. Serum albumin did not significantly improve in the whole group; however, when the total group was divided into groups according to hsCRP level, the group with a value of less than 10 had significant improvements in serum albumin, rising from 3.7 to 4.0 g/dL.
Finally, in a trial by Mehrotra et al (Am J Clin Nutr. 2009;90:1532-1540) eight patients were studied in a randomized cross-over design. The researchers used either sodium citrate or citric acid and ammonium chloride to adjust patients’ arterial pH levels. Nitrogen balance was assessed when the patients were either at a pH range of 7.36-7.38 or a range of 7.43-7.45. In this tightly controlled study, patients in the pH range of 7.43-7.45 had a significantly higher nitrogen balance.
Metabolic acidosis occurs frequently in both pre-dialysis and dialysis patients. However, correction with either sodium bicarbonate or sodium citrate is safe and effective. Furthermore, increased serum bicarbonate and pH levels have been shown to have beneficial effects on CKD progression and protein catabolism potentially resulting in improved nutritional status.
Dr. Steiber is Coordinator of the Dietetic Internship/Master’s Degree Program at Case Western Reserve University in Cleveland.