TY - JOUR
T1 - Effects of Sodium Bicarbonate in CKD Stages 3 and 4
T2 - A Randomized, Placebo-Controlled, Multicenter Clinical Trial
AU - Melamed, Michal L.
AU - Horwitz, Edward J.
AU - Dobre, Mirela A.
AU - Abramowitz, Matthew K.
AU - Zhang, Liping
AU - Lo, Yungtai
AU - Mitch, William E.
AU - Hostetter, Thomas H.
N1 - Funding Information:
Michal L. Melamed, MD, MHS, Edward J. Horwitz, MD, Mirela A. Dobre, MD, Matthew K. Abramowitz, MD, MS, Liping Zhang, PhD, Yungtai Lo, PhD, William E. Mitch, MD, and Thomas H. Hostetter, MD. Designed study: MLM, MKA, WEM, THH; recruited participants and ran the study protocol: MLM, EJH, MAD, MKA, THH; analyzed the data: MLM, MKA, LZ, YL. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. This study was funded by the NIH/National Institute of Diabetes and Digestive and Kidney Diseases through grant U01 DK087783. The funding source played no role in study design; data collection, analysis, or reporting; or the decision to submit for publication. The authors declare that they have no relevant financial interests. The authors will share deidentified participant-level data collected during the trial that underlie the results reported in this article. The study protocol will also be available on request. The data will be available 6 months after publication and ending 4 years after publication of this article. The data will be shared with researchers who provide a methodologically sound proposal for analyses pertaining to the aims in the proposal. Proposals should be e-mailed directly to michal.melamed@einstein.yu.edu. Data requesters will need to sign a data use agreement. Received February 25, 2019. Evaluated by 2 external peer reviewers and a statistician, with direct editorial input from an Associate Editor, who served as Acting Editor-in-Chief. Accepted in revised form July 16, 2019. The involvement of an Acting Editor-in-Chief was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.
Funding Information:
This study was funded by the NIH / National Institute of Diabetes and Digestive and Kidney Diseases through grant U01 DK087783 . The funding source played no role in study design; data collection, analysis, or reporting; or the decision to submit for publication.
Publisher Copyright:
© 2019 National Kidney Foundation, Inc.
PY - 2020/2
Y1 - 2020/2
N2 - Rationale & Objective: Metabolic acidosis associated with chronic kidney disease (CKD) may contribute to muscle dysfunction and bone disease. We aimed to test whether treatment with sodium bicarbonate improves muscle and bone outcomes. Study Design: Multicenter, randomized, placebo-controlled, clinical trial. Setting & Participants: 149 patients with CKD stages 3 and 4 between July 2011 and April 2016 at 3 centers in Cleveland, OH, and the Bronx, NY. Intervention: Sodium bicarbonate (0.4 mEq per kg of ideal body weight per day) (n = 74) or identical-appearing placebo (n = 75). Outcomes: Dual primary outcomes were muscle function assessed using sit-to-stand test and bone mineral density. Muscle biopsies were performed at baseline and 2 months. Participants were seen at baseline and 2, 6, 12, and 24 months. Results: Mean baseline serum bicarbonate level was 24.0 ± 2.2 (SD) mEq/L and mean baseline estimated glomerular filtration rate was 36.3 ± 11.2 mL/min/1.73 m2. Baseline characteristics did not differ between groups. Mean serum bicarbonate levels in the intervention arm during follow-up were 26.4 ± 2.2, 25.5 ± 2.3, 25.6 ± 2.6, and 24.4 ± 2.8 mEq/L (at 2, 6, 12, and 24 months). These were significantly higher than in the placebo group (P < 0.001). Compared to the placebo group, participants randomly assigned to sodium bicarbonate treatment had no significant differences in sit-to-stand time (5 repetitions: P = 0.1; and 10 repetitions P = 0.07) or bone mineral density (P = 0.3). Sodium bicarbonate treatment caused a decrease in serum potassium levels that was of borderline statistical significance (P = 0.05). There were no significant differences in estimated glomerular filtration rates, blood pressure, weight, serious adverse events, or levels of muscle gene expression between the randomly assigned groups. Limitations: Initial mean serum bicarbonate level was in the normal range. Conclusions: Sodium bicarbonate therapy in patients with CKD stages 3 and 4 significantly increases serum bicarbonate and decreases potassium levels. No differences were found in muscle function or bone mineral density between the randomly assigned groups. Larger trials are required to evaluate effects on kidney function. Funding: National Institutes of Health grant. Trial Registration: Registered at ClinicalTrials.gov
AB - Rationale & Objective: Metabolic acidosis associated with chronic kidney disease (CKD) may contribute to muscle dysfunction and bone disease. We aimed to test whether treatment with sodium bicarbonate improves muscle and bone outcomes. Study Design: Multicenter, randomized, placebo-controlled, clinical trial. Setting & Participants: 149 patients with CKD stages 3 and 4 between July 2011 and April 2016 at 3 centers in Cleveland, OH, and the Bronx, NY. Intervention: Sodium bicarbonate (0.4 mEq per kg of ideal body weight per day) (n = 74) or identical-appearing placebo (n = 75). Outcomes: Dual primary outcomes were muscle function assessed using sit-to-stand test and bone mineral density. Muscle biopsies were performed at baseline and 2 months. Participants were seen at baseline and 2, 6, 12, and 24 months. Results: Mean baseline serum bicarbonate level was 24.0 ± 2.2 (SD) mEq/L and mean baseline estimated glomerular filtration rate was 36.3 ± 11.2 mL/min/1.73 m2. Baseline characteristics did not differ between groups. Mean serum bicarbonate levels in the intervention arm during follow-up were 26.4 ± 2.2, 25.5 ± 2.3, 25.6 ± 2.6, and 24.4 ± 2.8 mEq/L (at 2, 6, 12, and 24 months). These were significantly higher than in the placebo group (P < 0.001). Compared to the placebo group, participants randomly assigned to sodium bicarbonate treatment had no significant differences in sit-to-stand time (5 repetitions: P = 0.1; and 10 repetitions P = 0.07) or bone mineral density (P = 0.3). Sodium bicarbonate treatment caused a decrease in serum potassium levels that was of borderline statistical significance (P = 0.05). There were no significant differences in estimated glomerular filtration rates, blood pressure, weight, serious adverse events, or levels of muscle gene expression between the randomly assigned groups. Limitations: Initial mean serum bicarbonate level was in the normal range. Conclusions: Sodium bicarbonate therapy in patients with CKD stages 3 and 4 significantly increases serum bicarbonate and decreases potassium levels. No differences were found in muscle function or bone mineral density between the randomly assigned groups. Larger trials are required to evaluate effects on kidney function. Funding: National Institutes of Health grant. Trial Registration: Registered at ClinicalTrials.gov
KW - Chronic kidney disease (CKD)
KW - alkali therapy
KW - bone mineral density
KW - metabolic acidosis
KW - metabolic bone disease
KW - muscle function
KW - randomized controlled trial (RCT)
KW - sit-to-stand
KW - sodium bicarbonate
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U2 - 10.1053/j.ajkd.2019.07.016
DO - 10.1053/j.ajkd.2019.07.016
M3 - Article
C2 - 31699517
AN - SCOPUS:85075376158
SN - 0272-6386
VL - 75
SP - 225
EP - 234
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 2
ER -