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 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 3939 participants with CKD stages 2-4 who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 - December 2008. Predictor Serum bicarbonate. Outcomes Renal outcomes, defined as end-stage renal disease (either initiation of dialysis or kidney transplantation) or 50% reduction in eGFR; atherosclerotic events (myocardial infarction, stroke, peripheral arterial disease); congestive heart failure events; and death. Measurements Time to event. Results The mean eGFR was 44.8 ± 16.8 (SD) mL/min/1.73 m2, and the median serum bicarbonate was 24 (IQR, 22-26) mEq/L. During a median follow-up of 3.9 years, 374 participants died, 767 had a renal outcome, and 332 experienced an atherosclerotic event and 391 had a congestive heart failure event. In adjusted analyses, the risk of developing a renal endpoint was 3% lower per mEq/L increase in serum bicarbonate (HR, 0.97; 95% CI, 0.94-0.99; p=0.01). The association was stronger for participants with eGFR> 45ml/min/1.73m2 (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 mEq/L increase in serum bicarbonate over 24 mEq/L. Serum bicarbonate was not independently associated 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 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. There was no association between serum bicarbonate and all-cause mortality or atherosclerotic events.

Metabolic acidosis status and mortality in patients on the end stage of renal disease

“…Acidemia is believed to be an important cause of adverse consequences and it is associated with an increased relative risk for death in dialysis patients. [9,21,22] In agreement to the above, in our data also we found significant impact of the serum bicarbonate concentrations, which was divided into three levels, on the overall mortality during our median follow up time of 60 months. Also, the serum bicarbonate concentrations were independent predictors for mortality rate after the adjustment for dialysis adequacy and age.…”

Retinopathy and Progression of CKD

“…Ascertainment of ESRD in the CRIC study was supplemented by linkage with the US Renal Data System. The second approach utilized the slope of change of eGFR, in which eGFR was calculated using a CRIC internal GFR estimating equation derived from iothalamate 125 clearance testing that incorporated information on serum creatinine, serum cystatin C, age, sex, and race (13,14). We also used a composite of ESRD and 50% decline in eGFR; however, because the results were very similar, we did not include them.…”

Study of association of serum bicarbonate levels with mortality in chronic kidney disease

“…4,5,16 Hence it is essential to optimize serum bicarbonates with oral supplementation. [6][7][8][9] According to present study it was noted that the incidence of Chronic Kidney Disease varied from minimum age of 20 years to maximum age of 88 years (Table 1). In the present study, maximum cases were found in 6th decade followed by 5 th decade (Table 2).…”

“…6,7 Studies have shown that low serum bicarbonate is associated with progression of kidney disease and increased mortality. 8 Due to the limited availability of studies done in Indian population this study was undertaken to assess the serum bicarbonate levels in different stages of CKD and its effect.…”