Low serum bicarbonate and kidney function decline: the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

Background: Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear.

Study design: Retrospective cohort study.

Setting & participants: 5,810 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) > 60mL/min/1.73 m(2) using the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation.

Predictors: Serum bicarbonate concentrations.

Outcomes: Rapid kidney function decline (eGFR decline > 5% per year) and incident reduced eGFR (eGFR < 60mL/min/1.73 m(2) with minimum rate of eGFR loss of 1 mL/min/1.73 m(2) per year).

Results: Average bicarbonate concentration was 23.2 ± 1.8mEq/L. 1,730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%-20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03-1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate level < 21 mEq/L relative to 23-24 mEq/L was 1.35 (95% CI, 1.05-1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83-1.62) for incident reduced eGFR.

Limitations: Cause of metabolic acidosis cannot be determined in this study.

Conclusions: Lower serum bicarbonate concentrations are associated independently with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with baseline eGFR > 60 mL/min/1.73 m(2). If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria or may have a causal role in the development of eGFR < 60 mL/min/1.73 m(2).

Keywords: Serum bicarbonate; chronic kidney disease (CKD); disease progression; kidney disease trajectory; kidney function; metabolic acidosis; renal disease.

Figure 1

Distribution of serum bicarbonate. The distribution of baseline serum bicarbonate concentrations (n=5,810) was normal with a mean level of 23 +/− 1.8 (SD) mEq/L.

Figure 2

Figure 2a: Adjusted association of serum bicarbonate with risk of rapid kidney function decline in MESA. Spline analysis adjusted for age, race, gender, education, diabetes mellitus, hypertension, smoking, BMI, HDL, eGFR, diuretic use and albuminuria. Solid line represents the point estimate and dotted lines represent 95% CI. Figure 2b: Adjusted association of serum bicarbonate with risk of incident reduced eGFR in MESA. Spline analysis adjusted for age, race, gender, education, diabetes mellitus, hypertension, smoking, BMI, HDL, eGFR, diuretic use and albuminuria). Solid line represents the point estimate and dotted lines represent 95% CI.