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.”