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 m2, 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 m2 (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.
Bibliographical noteFunding Information:
Support: Funding for the CRIC Study was obtained under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases ( U01DK060990 , U01DK060984 , U01DK061022 , U01DK061021 , U01DK061028 , U01DK060980 , U01DK060963 , and U01DK060902 ). In addition, this work was supported in part by the University of Pennsylvania Clinical and Translational Research Center Clinical and Translational Science Award (CTSA) UL1 RR-024134 , Johns Hopkins University UL1 RR-025005 , University of Maryland General Clinical Research Center (GCRC) M01 RR-16500 , Case Western Reserve University Clinical and Translational Science Collaborative of Cleveland , UL1TR000439 from the National Center for Advancing Translational Sciences component of the National Institutes of Health (NIH) and NIH roadmap for Medical Research, University of Michigan GCRC grant M01 RR-000042 , CTSA grant UL1 RR-024986 , University of Illinois at Chicago CTSA grant UL1RR029879 , The Clinical and Translational Research, Education, and Commercialization Project, Kaiser NIH/National Center for Research Resources University of California, San Francisco-Clinical and Translational Science Institute UL1 RR-024131 .
- Metabolic acidosis
- cardiovascular morbidity
- chronic kidney disease
- serum bicarbonate