Effects of Treatment of Metabolic Acidosis in CKD: A Systematic Review and Meta-Analysis

Abstract

Background and objectives: Metabolic acidosis is associated with progression of CKD and has significant adverse effects on muscle and bone. A systematic review and meta-analysis was conducted to evaluate the benefits and risks of metabolic acidosis treatment with oral alkali supplementation or a reduction of dietary acid intake in those with CKD.

Design, setting, participants, & measurements: MEDLINE, Embase, and Cochrane CENTRAL were searched for relevant trials in patients with stage 3-5 CKD and metabolic acidosis (<22 mEq/L) or low-normal serum bicarbonate (22-24 mEq/L). Data were pooled in a meta-analysis with results expressed as weighted mean difference for continuous outcomes and relative risk for categorical outcomes with 95% confidence intervals (95% CIs), using a random effects model. Study quality and strength of evidence were assessed using Cochrane risk of bias and the Grading of Recommendations Assessment, Development and Evaluation criteria.

Results: Fourteen clinical trials were included (n=1394 participants). Treatment of metabolic acidosis with oral alkali supplementation or a reduction of dietary acid intake increased serum bicarbonate levels (14 studies, 1378 patients, mean difference 3.33 mEq/L, 95% CI, 2.37 to 4.29) and resulted in a slower decline in eGFR (13 studies, 1329 patients, mean difference -3.28 ml/min per 1.73 m², 95% CI, -4.42 to -2.14; moderate certainty) and a reduction in urinary albumin excretion (very-low certainty), along with a reduction in the risk of progression to ESKD (relative risk, 0.32; 95% CI, 0.18 to 0.56; low certainty). Oral alkali supplementation was associated with worsening hypertension or the requirement for increased antihypertensive therapy (very-low certainty).

Conclusions: Low-to-moderate certainty evidence suggest that oral alkali supplementation or a reduction in dietary acid intake may slow the rate of kidney function decline and potentially reduce the risk of ESKD in patients with CKD and metabolic acidosis.

Keywords: Albumins; Alkalies; Antihypertensive Agents; Bias; Bicarbonates; Confidence Intervals; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Risk Assessment; acidosis; chronic metabolic acidosis; glomerular filtration rate; hypertension; kidney disease; sodium bicarbonate.

Graphical abstract

Figure 1.

Flow chart showing number of citations retrieved by individual searches and number of trials included in the systematic review.

Figure 2.

Forest plot shows slower decline in eGFR at the end of study period with oral akali supplementation or reduction of dietary acid intake. I² for the combined effect estimate: 39% (95% CI, 0% to 66%). df, degrees of freedom; IV, inverse variance.

Figure 3.

Forest plot shows slower decline in eGFR per year with oral akali supplementation or reduction of dietary acid intake. I² for the combined effect estimate: (95% CI, 0% to 53%). df, degrees of freedom; IV, inverse variance.

Figure 4.

Forest plot shows potentially reduced risk of end stage kidney disease with oral alkali supplementation or reduction of dietary acid intake. I² for the combined effect estimate: (95% CI, 0% to 73%). df, degrees of freedom; M-H, Mantel-Haenszel.