Patients with nondialysis-dependent chronic kidney disease (CKD) who have metabolic acidosis may be at increased risk for major adverse cardiovascular events (MACEs).

In a study of 51,558 adults with stage 3-5 CKD from The Optum® De-identified Electronic Health Records Dataset (2007-2017), a total of 34% had a low serum bicarbonate level (12 or higher but less than 22 mEq/L). Metabolic acidosis at baseline was associated with a higher rate of the primary composite MACE endpoint during follow-up compared with normal serum bicarbonate levels of 22-29 mEq/L (58% vs 44%), Navdeep Tangri MD, PhD, of the University of Manitoba, Winnipeg, Manitoba, Canada, and colleagues reported in Kidney Medicine. In an adjusted Cox proportional hazards model, every 1-mEq/L increase in serum bicarbonate was associated with a 4% decrease in the risk for composite MACEs. Each increment of serum bicarbonate also was associated with a 2%, 2%, 4%, and 6% decreased risk of the individual components of MACE, including incident heart failure, stroke, myocardial infarction, and cardiovascular death, respectively.

Compared with White patients, Black patients had a 29% increased risk for composite MACE and 28%, 27%, 12%, and 31% increased risks for each of the individual components of MACE, respectively. Pre-existing diabetes, heart failure, coronary artery disease, and peripheral vascular disease were associated with higher risks for MACE and its components. Patients with metabolic acidosis were more likely to have each of these comorbidities.

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The investigators adjusted for age, race, kidney function, serum albumin, hemoglobin, and these comorbidities, but they could not account for all relevant variables, such as diet, respiratory disorders (besides chronic obstructive pulmonary disease), diuretic and statin use, smoking, and blood pressure.

According to the investigators, metabolic acidosis is postulated to be a CKD-specific cardiovascular risk factor because of its negative effects on the cardiovascular system, including inflammation and activation of the renin-angiotensin-aldosterone system..

“Further research is needed to explain the mechanisms that drive the association between metabolic acidosis and [cardiovascular] events, and randomized controlled trials are needed to examine if the correction of acidosis in CKD improves [cardiovascular] morbidity and mortality,” Dr Tangri’s team concluded.

Disclosure: This research was supported by Tricida. Please see the original reference for a full list of disclosures.


Collister D, Ferguson TW, Funk SE, Reaven NL, Mathur V, Tangri N. Metabolic acidosis and cardiovascular disease in CKD. Kidney Med. Published online June 28, 2021. doi:10.1016/j.xkme.2021.04.011

This article originally appeared on Renal and Urology News