Association of serum bicarbonate with risk of renal and cardiovascular outcomes in CKD: a report from the Chronic Renal Insufficiency Cohort (CRIC) study

Abstract

Background: The purpose of this study is to evaluate serum bicarbonate level as a risk factor for renal outcomes, cardiovascular events, and mortality in patients with chronic kidney disease (CKD).

Study design: Observational cohort study.

Setting & participants: 3,939 participants with CKD stages 2-4 who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 and December 2008.

Predictor: Serum bicarbonate level.

Outcomes: Renal outcomes, defined as end-stage renal disease (either initiation of dialysis therapy or kidney transplantation) or 50% reduction in estimated glomerular filtration rate (eGFR); atherosclerotic events (myocardial infarction, stroke, or peripheral arterial disease); congestive heart failure events; and death.

Measurements: Time to event.

Results: Mean eGFR was 44.8 ± 16.8 (SD) mL/min/1.73 m(2), and median serum bicarbonate level was 24 (IQR, 22-26) mEq/L. During a median follow-up of 3.9 years, 374 participants died, 767 had a renal outcome, 332 experienced an atherosclerotic event, and 391 had a congestive heart failure event. In adjusted analyses, the risk of developing a renal end point was 3% lower per 1-mEq/L increase in serum bicarbonate level (HR, 0.97; 95% CI, 0.94-0.99; P = 0.01). The association was stronger for participants with eGFR >45 mL/min/1.73 m(2) (HR, 0.91; 95% CI, 0.85-0.97; P = 0.004). The risk of heart failure increased by 14% (HR, 1.14; 95% CI, 1.03-1.26; P = 0.02) per 1-mEq/L increase in serum bicarbonate level over 24 mEq/L. Serum bicarbonate level was not associated independently with atherosclerotic events (HR, 0.99; 95% CI, 0.95-1.03; P = 0.6) and all-cause mortality (HR, 0.98; 95% CI, 0.95-1.02; P = 0.3).

Limitations: Single measurement of sodium bicarbonate.

Conclusions: In a cohort of participants with CKD, low serum bicarbonate level was an independent risk factor for kidney disease progression, particularly for participants with preserved kidney function. The risk of heart failure was higher at the upper extreme of serum bicarbonate levels. There was no association between serum bicarbonate level and all-cause mortality or atherosclerotic events.

Keywords: Metabolic acidosis; cardiovascular morbidity; chronic kidney disease; serum bicarbonate.

Figure 1

Unadjusted event rates by quartile of serum bicarbonate (mEq/L).

Figure 2

Serum bicarbonate and risk of renal disease in subgroups defined by race, diabetes, eGFR and urine protein.

Figure 3

Serum bicarbonate and risk of death in subgroups defined by race, diabetes, eGFR and urine protein excretion.

Figure 4

Association between serum bicarbonate (mEq/L) and heart failure events (Panel A and B) Panel A. Adjusted quadratic spline model for heart failure events Panel B. Adjusted quadratic spline model for heart failure events excluding participants with cardiovascular disease at baseline. The solid line represents the effect and the dashed lines represent the confidence intervals. There was a trend toward a “U shape” association between serum bicarbonate and heart failure events, though it only reached statistical significance for participants with serum bicarbonate in the alkalotic range.