Metabolic acidosis increases risk for adverse cardiovascular events in patients with CKD
The presence of metabolic acidosis increased the risk for major adverse cardiovascular events in patients with non-dialysis dependent chronic kidney disease, study findings showed.
“The prevalence of metabolic acidosis, defined by a reduced serum bicarbonate level, increases as glomerular filtration rate (GFR) decreases. Both the decrease in serum bicarbonate and net acid excretion in CKD are associated with an accelerated decline in GFR and end-stage kidney disease (ESKD) in addition to adverse musculoskeletal effects and increased mortality,” David Collister, MD, clinical scholar in the department of medicine at McMaster University, Ontario, and colleagues wrote. “Metabolic acidosis is postulated to be a CKD-specific CV risk factor because of its negative effects on the CV system, including inflammation and activation of the renin-angiotensin-aldosterone system (RAAS). Prior studies have not clearly elucidated an effect of metabolic acidosis on the risk of CV events.”
To shed light on this area, Collister and colleagues conducted a retrospective, community-based cohort study of 51,558 adults with CKD stages 3 through 5, categorizing participants into groups based on serum bicarbonate levels (two consecutive measurements were taken 28 to 365 days apart; metabolic acidosis was said to be present with serum bicarbonate levels of 12 mEq per L to 22 mEq per L).
Researchers considered the occurrence of major adverse cardiovascular events (as a composite outcome and as individual components of heart failure, stroke, myocardial infarction and CV-related death) during a median follow-up period of 3.9 to 4.5 years.
Adjustments were made for age, sex, race, eGFR, diabetes, hypertension, coronary artery disease, peripheral vascular disease, hemoglobin and serum albumin.
Metabolic acidosis was more common in younger patients (mean age of 70 years vs. 74 years), African American patients (15% vs. 7% for white patients), as well as in those with more advanced CKD and a greater burden of comorbidities.
Overall, 48% of the study population experienced a MACE-plus event within 2 years, with researchers determining metabolic acidosis at baseline to be associated with a higher rate of MACE-plus events (58% vs. 44%).
Further, for every 1-mEq per L increase in serum bicarbonate, researchers observed a 4% decrease in the risk of MACE-plus events (adjusted hazard ratio of 0.96).
The reduced risk for cardiovascular events with increasing serum bicarbonate was also observed for individual components, including incident heart failure (aHR = 0.98), stroke (aHR = 0.98), myocardial infarction (aHR = 0.96) and CV death (aHR = 0.94).
“Given the high CV event rates in the CKD population and underdiagnosis and undertreatment of metabolic acidosis, these findings suggest a potential opportunity for reduction in the risk of CV events,” Collister and colleagues concluded. “ ... Further research is needed to explain the mechanisms that drive the association between metabolic acidosis and CV events, and randomized controlled trials are needed to examine if the correction of acidosis in CKD improves CV morbidity and mortality.”
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