Treating Metabolic Acidosis in Patients with CKD: A Systematic Review and Meta-Analysis

Patients with chronic kidney disease (CKD) and metabolic acidosis are at increased risk for CKD progression and experience significant muscle- and bone-related adverse events. Sankar D. Navaneethan, MD, MS, MPH, and colleagues conducted a systematic review and meta-analysis to examine the benefits and risks of treatment of metabolic acidosis with oral alkali supplementation or a reduction of dietary acid intake in patients with CKD. Results of the review were reported in the Clinical Journal of the American Society of Nephrology [2019;14(7):1011-1020].

Relevant trials involving patients with stage 3-5 CKD and metabolic acidosis (<22 mEq/L) or low-normal serum bicarbonate (22-24 mEq/L) were identified via searches in MEDLINE, Embase, and Cochrane CENTRAL. Data were pooled in a meta-analysis, and random effects models were used to express results as weighted mean difference for continuous outcomes and relative risk for categorical outcomes with 95% confidence intervals (CI). Cochrane risk of bias and criteria from the Grading of Recommendations Assessment, Development, and Evaluation were used to assess study quality and strength of evidence.

The meta-analysis included 14 trials representing 1394 participants. In the 14 studies, serum bicarbonate levels were increased with treatment of metabolic acidosis with oral alkali supplementation or a reduction in dietary acid intake (1378 patients; mean difference, 3.33 mEq/L; 95% CI, 2.37-4.29). In 13 studies, treatment resulted in a slower decline in estimated glomerular filtration rate (1329 patients; mean difference, –3.28 mL/min/1.73 m2; 95% CI, –4.42 to –2.14; moderate certainty), as well as a reduction in urinary albumin excretion (very-low certainty) and a reduction in the risk of progression to end-stage renal disease (ESRD; relative risk, 0.32; 95% CI, 0.18-0.56; low certainty). There was an association between oral alkali supplementation and worsening hypertension or the need for increased antihypertensive therapy (very-low certainty).

In summary, the researchers said, “Current clinical trial evidence suggests that oral alkali supplementation or a reduction of dietary acid load improved serum bicarbonate levels and may slow the progression of kidney disease on the basis of very-low- to moderate-certainty clinical evidence. Further larger, long-term studies of better quality are warranted to establish the benefits (such as delaying initiation of kidney replacement therapy or slowing progression to ESRD) and risks of treatment with oral alkali and/or a reduction in dietary acid load in patients with CKD.”