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 m(2), 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.