A Systematic Review and Meta-Analysis on Effects of Bicarbonate Therapy on Kidney Outcomes

Sebastian Hultin; Chris Hood; Katrina L Campbell; Nigel D Toussaint; David W Johnson; Sunil V Badve

doi:10.1016/j.ekir.2020.12.019

A Systematic Review and Meta-Analysis on Effects of Bicarbonate Therapy on Kidney Outcomes

Kidney Int Rep. 2020 Dec 31;6(3):695-705. doi: 10.1016/j.ekir.2020.12.019. eCollection 2021 Mar.

Authors

Sebastian Hultin^{1

2

3}, Chris Hood^{1

4}, Katrina L Campbell^{1

5}, Nigel D Toussaint^{1

6}, David W Johnson^{1

7

8}, Sunil V Badve^{1

3

9}

Affiliations

¹ Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia.
² University of Sydney, Sydney, Australia.
³ Department of Nephrology, St George Hospital, Sydney, Australia.
⁴ Department of Nephrology, Middlemore Hospital, Auckland, New Zealand.
⁵ Healthcare Excellence and Innovation, Metro North Hospital and Health Service, Brisbane, Australia.
⁶ Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia.
⁷ Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia.
⁸ Translational Research Institute, Brisbane, Australia.
⁹ The George Institute for Global Health, University of New South Wales Medicine, Sydney, Australia.

Abstract

Aim: Preclinical studies suggest treatment of metabolic acidosis may slow chronic kidney disease (CKD) progression. This systematic review aimed to summarize evidence from randomized controlled trials (RCTs) concerning the benefits and risks of bicarbonate therapy on kidney outcomes.

Methods: Medline, EMBASE, and Cochrane databases were searched for RCTs with ≥3 months' follow-up in patients with CKD (estimated glomerular filtration rate [eGFR] ≤60 ml/min per 1.73 m² and/or proteinuria) comparing the effects of sodium bicarbonate with placebo/no study medication on kidney outcomes. The primary outcome was change from baseline to last measurement in kidney function measured as either eGFR or creatinine clearance. Treatment effects were summarized using random-effects meta-analysis.

Results: Fifteen trials (2445 participants, median follow-up 12 months) were eligible for inclusion. Compared with placebo or no study medication, sodium bicarbonate retarded the decline in kidney function (standardized mean difference [SMD]: 0.26; 95% confidence interval [CI]: 0.13-0.40; I ² = 50%, low certainty evidence), and reduced the risk of end-stage kidney failure (risk ratio [RR]: 0.53; 95% CI 0.32-0.89; I ² = 69%, low certainty evidence). The effect of sodium bicarbonate on proteinuria (SMD: -0.09; 95% CI -0.27 to 0.09; I ² = 28%, very low certainty evidence), systolic blood pressure (weighted mean difference [WMD]: -0.57 mm Hg; 95% CI -2.32 to 1.18; I ² = 0%, low certainty evidence), all-cause death (RR: 0.81; 95% CI: 0.39-1.68; I ² = 30%; very low certainty evidence) and edema (RR: 1.16; 95% CI: 0.90-1.50; I ² = 28%; low certainty evidence) were uncertain.

Conclusion: Sodium bicarbonate may slow CKD progression. Adequately powered randomized trials are required to evaluate the benefits and risks of sodium bicarbonate in CKD.

Keywords: acidosis; bicarbonate therapy; chronic kidney disease; clinical trial; dialysis; kidney function tests; kidney replacement therapy.