Effects of Sodium Bicarbonate in CKD Stages 3 and 4: A Randomized, Placebo-Controlled, Multicenter Clinical Trial

Michal L. Melamed, Edward J. Horwitz, Mirela A. Dobre, Matthew K. Abramowitz, Liping Zhang, Yungtai Lo, William E. Mitch, Thomas H. Hostetter

Research output: Contribution to journalArticle

Abstract

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 with study number NCT01452412

Original languageEnglish (US)
JournalAmerican Journal of Kidney Diseases
DOIs
StateAccepted/In press - Jan 1 2019

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Sodium Bicarbonate
Controlled Clinical Trials
Chronic Renal Insufficiency
Multicenter Studies
Placebos
Muscles
Bicarbonates
Bone Density
Serum
Glomerular Filtration Rate
Ideal Body Weight
Organized Financing
Bone Diseases
National Institutes of Health (U.S.)
Therapeutics
Acidosis
Potassium
Reference Values
Randomized Controlled Trials
Blood Pressure

Keywords

  • alkali therapy
  • bone mineral density
  • Chronic kidney disease (CKD)
  • metabolic acidosis
  • metabolic bone disease
  • muscle function
  • randomized controlled trial (RCT)
  • sit-to-stand
  • sodium bicarbonate

ASJC Scopus subject areas

  • Nephrology

Cite this

Effects of Sodium Bicarbonate in CKD Stages 3 and 4 : A Randomized, Placebo-Controlled, Multicenter Clinical Trial. / Melamed, Michal L.; Horwitz, Edward J.; Dobre, Mirela A.; Abramowitz, Matthew K.; Zhang, Liping; Lo, Yungtai; Mitch, William E.; Hostetter, Thomas H.

In: American Journal of Kidney Diseases, 01.01.2019.

Research output: Contribution to journalArticle

Melamed, Michal L. ; Horwitz, Edward J. ; Dobre, Mirela A. ; Abramowitz, Matthew K. ; Zhang, Liping ; Lo, Yungtai ; Mitch, William E. ; Hostetter, Thomas H. / Effects of Sodium Bicarbonate in CKD Stages 3 and 4 : A Randomized, Placebo-Controlled, Multicenter Clinical Trial. In: American Journal of Kidney Diseases. 2019.
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abstract = "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 with study number NCT01452412",
keywords = "alkali therapy, bone mineral density, Chronic kidney disease (CKD), metabolic acidosis, metabolic bone disease, muscle function, randomized controlled trial (RCT), sit-to-stand, sodium bicarbonate",
author = "Melamed, {Michal L.} and Horwitz, {Edward J.} and Dobre, {Mirela A.} and Abramowitz, {Matthew K.} and Liping Zhang and Yungtai Lo and Mitch, {William E.} and Hostetter, {Thomas H.}",
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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.

PY - 2019/1/1

Y1 - 2019/1/1

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 with study number NCT01452412

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 with study number NCT01452412

KW - alkali therapy

KW - bone mineral density

KW - Chronic kidney disease (CKD)

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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