Evidence summary
Bicarbonate therapy demonstrates benefit in 2 meta-analyses
Two recent meta-analyses evaluated studies of bicarbonate therapy in patients with CKD, and both found benefit.1,2
A 2020 meta-analysis included 15 RCTs (N = 2445) of adults (mean age, 61 years; range, 40.5-73.9 years) with CKD.1 Most trials enrolled patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2; however, 1 study (N = 80) enrolled patients who had an eGFR of 60 to 90 mL/min/1.73 m2 and albuminuria, and another (N = 74) enrolled patients with an eGFR of 15 to 89 mL/min/1.73 m2. Four studies included patients with normal baseline bicarbonate levels, while the rest enrolled patients with metabolic acidosis. The primary outcome was CKD progression at study conclusion, which ranged from 3 to 60 months (median, 12 months).
Compared to placebo or no therapy, sodium bicarbonate (variously dosed) resulted in a small reduction in the rate of loss of kidney function (defined by eGFR or creatinine clearance) from baseline to trial completion (14 trials, N = 2073; standardized mean difference [SMD] = 0.26; 95% CI, 0.13-0.40; P = .018; I2 = 50%).1Sodium bicarbonate therapy also resulted in a moderate reduction in the risk of end-stage renal disease (7 trials, N = 1526; risk ratio [RR] = 0.53; 95% CI, 0.30-0.89; P = .011; I2 = 69%; number needed to treat [NNT] = 14).1 There was no difference in hospitalizations for heart failure, risk of worsening blood pressure, or all-cause mortality between the sodium bicarbonate and control groups.
Subgroup analysis by follow-up time found a significant preservation of eGFR only in studies with follow-up > 12 months (4 trials, N = 392; weighted mean difference = 3.71 mL/min/1.73 m2; 95% CI, 0.18-7.24; P = .042; I2 = 63%).1 Duration of therapy did not affect initiation of dialysis. Another subgroup analysis found that low- and moderate-quality studies were more likely than high-quality studies to find a change in the primary outcome. Overall, there was significant heterogeneity among the trials (control intervention, follow-up duration, methods of assessment of kidney function, dosage of sodium bicarbonate), as well as underrepresentation of female, pediatric, and elderly patients.
Another meta-analysis, published in 2019 by a different research group, analyzed 7 RCTs (N = 815) that comprised a subset of those in the newer analysis.2 The 2019 analysis similarly found that, compared to placebo or usual care, oral bicarbonate therapy resulted in statistically significantly higher eGFRs at 3 to 60 months’ follow-up (mean difference = 3.1 mL/min/1.73 m²; 95% CI, 1.3-4.9).2 The authors noted that the protective effect on eGFR was not seen in studies reporting outcomes at 1 year. Progression to end-stage renal disease or initiation of dialysis were not used as outcomes.
Significant outcomes seen in 1 large study
The largest study (N = 740) included in the 2020 meta-analysis (and discussed separately due to its size and duration) was a multicenter, unblinded, pragmatic trial investigating bicarbonate therapy in CKD.3 Patients were adults (mean age, 67.8 years) with CKD stages 3 to 5 and metabolic acidosis (serum bicarbonate level of 18-24 mmol/L); mean serum creatinine was 2.3 mg/dL, and mean serum bicarbonate was 21.5 mmol/L. Patients with severe heart failure or uncontrolled hypertension were excluded.
Researchers randomized patients to oral sodium bicarbonate (titrated to a target serum concentration of 24-28 mmol/L) or standard care for a median duration of 30 months. The primary endpoint was time to doubling of serum creatinine, and secondary endpoints included all-cause mortality, time to initiation of dialysis, hospitalization rate, and hospital length of stay.
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