Metabolic Acidosis and Cardiovascular Disease in CKD.

Rationale & Objective: Metabolic acidosis related to chronic kidney disease (CKD) is associated with an accelerated decline in glomerular filtration rate (GFR) and the development of end-stage kidney disease. Whether metabolic acidosis is associated with cardiovascular (CV) events in patients with CKD is unclear.

Study Design: Retrospective cohort study.

Setting & Participants: The Optum De-identified Electronic Health Records Dataset, 2007-2017, was used to generate a cohort of patients with non-dialysis-dependent CKD who had at least 3 estimated GFR < 60 mL/min/1.73 m. Patients with metabolic acidosis (serum bicarbonate 12 to <22 mEq/L) or normal serum bicarbonate (22‒29 mEq/L) at baseline were identified by 2 consecutive measurements 28‒365 days apart.

Predictor: Serum bicarbonate as a continuous variable.

Outcome: Primary outcome was a composite of major adverse cardiovascular events (MACE+). Secondary outcomes included individual components of the composite outcome.

Analytical Approach: Cox proportional hazards models to evaluate the association between 1-mEq/L increments in serum bicarbonate and MACE+.

Results: A total of 51,558 patients were evaluated, 34% had metabolic acidosis. The median follow-up period was 3.9-4.5 years, depending on the outcome assessed. The adjusted hazard ratio (HR) for MACE+ was 0.964 (95% CI, 0.961-0.968). For the individual components of incident heart failure (HF), stroke, myocardial infarction (MI), and CV death, HRs were 0.98 (95% CI, 0.97-0.98), 0.98 (95% CI, 0.97-0.99), 0.96 (95% CI, 0.96-0.97), and 0.94 (95% CI, 0.93-0.94), respectively, for every 1-mEq/L increase in serum bicarbonate.

Limitations: Possible residual confounding.

Conclusions: Metabolic acidosis in CKD is associated with an increased risk of MACE+ as well as the individual components of incident HF, stroke, MI, and CV death. Randomized controlled trials evaluating treatments for the correction of metabolic acidosis in CKD to prevent CV events are needed.