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Impact of Serum Bicarbonate Levels on Muscle Mass and Kidney Function in Pre-Dialysis Chronic Kidney Disease Patients.
Am J Nephrol. 2020; 51(1):24-34.AJ

Abstract

BACKGROUND

Treatment of metabolic acidosis to target the higher serum bicarbonate level than guideline recommendation may downregulate muscle protein degradation and improve renal function among chronic kidney disease (CKD) patients. We conducted a study to test the effects of increased serum bicarbonate level on muscle parameters, nutrition, and renal function in pre-dialysis CKD patients.

METHODS

This was a randomized, controlled study. CKD stage 3-4 patients with serum HCO3- <22 mEq/L were randomized to either receive oral sodium bicarbonate with high target bicarbonate level of 25 ± 1 or standard level of 22 ± 1 mEq/L as control group using protocol-based titration of dosage adjustment. The changes of muscle mass measured by bioelectrical impedance analysis (BIA), muscle strength by hand grip dynamometer, estimated glomerular filtration rate (eGFR) using CKD-Epidemiology Collaboration equation, nutritional markers, and muscle-related biomarkers were determined. Data at baseline and after 4 months of sodium bicarbonate supplementation were compared between groups using Student t test or chi-square test as appropriate.

RESULTS

Forty-two patients completed the study (n = 21 per group). The mean age and eGFR were 61.2 ± 9.8 years and 32.4 ± 14.1 mL/min respectively. Serum bicarbonate levels at baseline were 21.0 ± 2.1 mEq/L. Baseline data including sex, diabetes, serum bicarbonate level, creatinine, and blood pressure were similar. After 4 months of treatment, the average serum bicarbonate levels in both groups were 24.0 ± 1.4 and 20.7 ± 2.3 mEq/L (p < 0.001). Both BIA-derived total-body muscle mass and appendicular lean balance were increased at 4 months in the higher bicarbonate group (26.0 ± 5.3 to 26.7 ± 5.5 kg, p = 0.04 and 19.8 ± 4.1 to 20.7 ± 4.4 kg, p = 0.06, respectively) despite comparable body weight and protein intake. Patients in the high bicarbonate group had a significant reduction of plasma myostatin levels, a surrogate of muscle degradation, at the study exit after adjusting for baseline values (-3,137.8; 95% CI -6,235.3 to -40.4 pg/mL, p= 0.04), but unaltered insulin-like growth factor-1 level, as the mediator of muscle cell growth, (141 [106-156] to 110 [87-144] ng/mL, p = 0.13) compared to the control group. Muscle strength, eGFR as well as serum prealbumin were not significantly different between 2 groups (p > 0.05). Neither worsening hypertension nor congestive heart failure was found throughout the study.

CONCLUSION

Bicarbonate supplementation to achieve the serum level ∼24 mEq/L demonstrates better muscle mass preservation in patients with pre-dialysis CKD. The impact of alkaline therapy on renal function may require a longer period of study.

Authors+Show Affiliations

Division of Internal Medicine-Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. Special Task force for Activating Research in Renal Nutrition (Renal Nutrition Research Group), Office of Research Affairs, Chulalongkorn University, Bangkok, Thailand. Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Department of Medicine, Vichaiyut Medical Center, Bangkok, Thailand.Department of Surgery, Faculty of Medicine, Chulalongkorn University and Queen Sirikit Centre for Breast Cancer, Thai Red Cross Society, Bangkok, Thailand.Ramathibodi Comprehensive Cancer Center, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.Special Task force for Activating Research in Renal Nutrition (Renal Nutrition Research Group), Office of Research Affairs, Chulalongkorn University, Bangkok, Thailand. Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.Special Task force for Activating Research in Renal Nutrition (Renal Nutrition Research Group), Office of Research Affairs, Chulalongkorn University, Bangkok, Thailand, somchai80754@yahoo.com. Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, somchai80754@yahoo.com.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31752000

Citation

Kittiskulnam, Piyawan, et al. "Impact of Serum Bicarbonate Levels On Muscle Mass and Kidney Function in Pre-Dialysis Chronic Kidney Disease Patients." American Journal of Nephrology, vol. 51, no. 1, 2020, pp. 24-34.
Kittiskulnam P, Srijaruneruang S, Chulakadabba A, et al. Impact of Serum Bicarbonate Levels on Muscle Mass and Kidney Function in Pre-Dialysis Chronic Kidney Disease Patients. Am J Nephrol. 2020;51(1):24-34.
Kittiskulnam, P., Srijaruneruang, S., Chulakadabba, A., Thokanit, N. S., Praditpornsilpa, K., Tungsanga, K., & Eiam-Ong, S. (2020). Impact of Serum Bicarbonate Levels on Muscle Mass and Kidney Function in Pre-Dialysis Chronic Kidney Disease Patients. American Journal of Nephrology, 51(1), 24-34. https://doi.org/10.1159/000504557
Kittiskulnam P, et al. Impact of Serum Bicarbonate Levels On Muscle Mass and Kidney Function in Pre-Dialysis Chronic Kidney Disease Patients. Am J Nephrol. 2020;51(1):24-34. PubMed PMID: 31752000.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of Serum Bicarbonate Levels on Muscle Mass and Kidney Function in Pre-Dialysis Chronic Kidney Disease Patients. AU - Kittiskulnam,Piyawan, AU - Srijaruneruang,Somrath, AU - Chulakadabba,Adhisabandh, AU - Thokanit,Nintita Sripaiboonkij, AU - Praditpornsilpa,Kearkiat, AU - Tungsanga,Kriang, AU - Eiam-Ong,Somchai, Y1 - 2019/11/21/ PY - 2019/09/23/received PY - 2019/11/03/accepted PY - 2019/11/22/pubmed PY - 2021/2/9/medline PY - 2019/11/22/entrez KW - Chronic kidney disease KW - Lean body mass KW - Metabolic acidosis KW - Muscle mass KW - Renal function SP - 24 EP - 34 JF - American journal of nephrology JO - Am J Nephrol VL - 51 IS - 1 N2 - BACKGROUND: Treatment of metabolic acidosis to target the higher serum bicarbonate level than guideline recommendation may downregulate muscle protein degradation and improve renal function among chronic kidney disease (CKD) patients. We conducted a study to test the effects of increased serum bicarbonate level on muscle parameters, nutrition, and renal function in pre-dialysis CKD patients. METHODS: This was a randomized, controlled study. CKD stage 3-4 patients with serum HCO3- <22 mEq/L were randomized to either receive oral sodium bicarbonate with high target bicarbonate level of 25 ± 1 or standard level of 22 ± 1 mEq/L as control group using protocol-based titration of dosage adjustment. The changes of muscle mass measured by bioelectrical impedance analysis (BIA), muscle strength by hand grip dynamometer, estimated glomerular filtration rate (eGFR) using CKD-Epidemiology Collaboration equation, nutritional markers, and muscle-related biomarkers were determined. Data at baseline and after 4 months of sodium bicarbonate supplementation were compared between groups using Student t test or chi-square test as appropriate. RESULTS: Forty-two patients completed the study (n = 21 per group). The mean age and eGFR were 61.2 ± 9.8 years and 32.4 ± 14.1 mL/min respectively. Serum bicarbonate levels at baseline were 21.0 ± 2.1 mEq/L. Baseline data including sex, diabetes, serum bicarbonate level, creatinine, and blood pressure were similar. After 4 months of treatment, the average serum bicarbonate levels in both groups were 24.0 ± 1.4 and 20.7 ± 2.3 mEq/L (p < 0.001). Both BIA-derived total-body muscle mass and appendicular lean balance were increased at 4 months in the higher bicarbonate group (26.0 ± 5.3 to 26.7 ± 5.5 kg, p = 0.04 and 19.8 ± 4.1 to 20.7 ± 4.4 kg, p = 0.06, respectively) despite comparable body weight and protein intake. Patients in the high bicarbonate group had a significant reduction of plasma myostatin levels, a surrogate of muscle degradation, at the study exit after adjusting for baseline values (-3,137.8; 95% CI -6,235.3 to -40.4 pg/mL, p= 0.04), but unaltered insulin-like growth factor-1 level, as the mediator of muscle cell growth, (141 [106-156] to 110 [87-144] ng/mL, p = 0.13) compared to the control group. Muscle strength, eGFR as well as serum prealbumin were not significantly different between 2 groups (p > 0.05). Neither worsening hypertension nor congestive heart failure was found throughout the study. CONCLUSION: Bicarbonate supplementation to achieve the serum level ∼24 mEq/L demonstrates better muscle mass preservation in patients with pre-dialysis CKD. The impact of alkaline therapy on renal function may require a longer period of study. SN - 1421-9670 UR - https://www.unboundmedicine.com/medline/citation/31752000/Impact_of_Serum_Bicarbonate_Levels_on_Muscle_Mass_and_Kidney_Function_in_Pre_Dialysis_Chronic_Kidney_Disease_Patients_ L2 - https://www.karger.com?DOI=10.1159/000504557 DB - PRIME DP - Unbound Medicine ER -