Serum bicarbonate levels and the progression of kidney disease: a cohort study

Abstract

Background: Animal models of kidney disease have linked metabolic acidosis with renal damage. The role of low serum bicarbonate levels in kidney disease progression in humans has not been studied.

Study design: Retrospective cohort study.

Setting & participants: Adults visiting a medical clinic in the Bronx, NY, from January 1, 2001, to December 31, 2003, were included in the study (n = 5,422) and followed up until June 30, 2007.

Predictor: Serum bicarbonate level.

Outcomes: Kidney disease progression was defined as either a decrease in estimated glomerular filtration rate (eGFR) by 50% or reaching an eGFR less than 15 mL/min/1.73 m(2) (n = 337).

Measurements: Patients' baseline demographics, comorbid conditions, laboratory data, and socioeconomic status were recorded. Serial outpatient serum creatinine levels were collected (median, 5 measurements/person).

Results: Mean age was 52 years, 69% were women, 45% were African American, 31% were Hispanic, 21% had diabetes mellitus, 41% had hypertension, and 9% had a baseline eGFR less than 60 mL/min/1.73 m(2). Kidney disease progressed as defined in 337 patients (6.2%). Compared with the reference group (bicarbonate level, 25 to 26 mEq/L), hazard ratios for progression after adjustment for potential confounders were 1.54 (95% confidence interval [CI], 1.13 to 2.09) for bicarbonate levels of 22 mEq/L or less, 0.97 (95% CI, 0.70 to 1.35) for 23 to 24 mEq/L, and 1.14 (95% CI, 0.84 to 1.55) for 27 mEq/L or greater (global P for inclusion of serum bicarbonate level in the model = 0.01). These results were similar using different definitions of the outcome (eGFR decrease of 30%, 1,288 outcomes [24%]; or doubling of serum creatinine level, 268 outcomes [4.9%]).

Limitations: Data used in the study were collected for clinical, not research, purposes.

Conclusions: Low serum bicarbonate level is associated with progression of kidney disease independent of baseline eGFR and other clinical, demographic, and socioeconomic factors. Prospective studies are needed to confirm this relationship and evaluate the efficacy of alkali supplements for slowing progression.

Figures

Figure 1A

Relationship between serum bicarbonate level and eGFR category in 5,422 medical patients. White line in box plot represents the median, top and bottom of box represent the 75th and 25th percentiles and the very top and bottom lines represent the 95th and 5th percentiles of values.

Figure 1B

Relationship between serum anion gap and eGFR category in 5,422 medical patients. White line in box plot represents the median, top and bottom of box represent the 75th and 25th percentiles and the very top and bottom lines represent the 95th and 5th percentiles of values.

Figure 2

Association between serum bicarbonate quartiles and the risk of kidney disease progression in 5,422 medical patients. Multivariable adjusted for age, sex, race/ethnicity, diagnosis of diabetes mellitus, hypertension, and/or cardiovascular disease, calcium, hemoglobin, BUN, baseline eGFR, median income and insurance status.