In this issue, Dobre et al1 reported an observational study looking at results of annually measured serum bicarbonate concentration in participants with chronic kidney disease (CKD) enrolled in the Chronic Renal Insufﬁciency Cohort (CRIC) using the marginal structural model, a validated statistical method,2 to estimate the cumulative effect over the period of the study and their effects on adjudicated heart failure events, atherosclerotic events, renal disease progression, and mortality. In their analysis, they included patients aged 21 to 74 years with estimated glomerular ﬁltration rate of 20 to 70 mL/min per 1.73 m2 and excluded patients with NYHA Class III/IV heart failure. The ﬁnal study population of this analysis included 3586 participants. They adjusted all models for age, gender, race/ethnicity, clinical center, estimated glomerular ﬁltration rate, proteinuria, diabetes, systolic blood pressure, cardiovascular disease at baseline, chronic obstructive pulmonary disease, tobacco use, diuretic and alkali medication used, low-density lipoprotein, Fibroblast growth factor-23 (FGF-23), and high-sensitivity C-reactive protein. In their analysis, over an average of 6 years of followup, they found a statistically signiﬁcant higher rate of heart failure events and mortality in participants who maintained serum bicarbonate >26 mmol/L, while participants who maintained serum bicarbonate <22 mmol/L had increased risk of renal disease progression deﬁned as halving of estimated glomerular ﬁltration rate or end-stage renal disease. On the other hand, there was no association between serum bicarbonate levels and atherosclerotic cardiovascular events. In subgroup analysis, the relationship between serum bicarbonate concentration and heart failure and renal events was consistent across categories of race/ ethnicity, diabetes, or baseline kidney function. The strength of association between serum bicarbonate >26 and <22 and heart failure and renal events, respectively, persisted after excluding participants taking alkali therapy, or who had chronic obstructive pulmonary disease (COPD) or cardiovascular disease at baseline. On the other hand, the study was not powered to exclude participants on diuretic therapy (60% of the study cohort were taking diuretics), which is a major cause of metabolic alkalosis.
Khitan ZJ. Elevated serum bicarbonate concentration in chronic kidney disease: a call to find the cause. Journal of the American Heart Association 2015;4:e001997.