Serum bicarbonate and mortality in stage 3 and stage 4 chronic kidney disease

Abstract

Background and objectives: The incidence and prevalence of metabolic acidosis increase with declining kidney function. We studied the associations of both low and high serum bicarbonate levels with all-cause mortality among stage 3 and 4 chronic kidney disease (CKD) patients.

Design, setting, participants, & measurements: We examined factors associated with low (<23 mmol/L) and high (>32 mmol/L) serum bicarbonate levels using logistic regression models and associations between bicarbonate and all-cause mortality using Cox-proportional hazard models, Kaplan-Meier survival curves, and time-dependent analysis.

Results: Out of 41,749 patients, 13.9% (n = 5796) had low and 1.6% (n = 652) had high serum bicarbonate levels. After adjusting for relevant covariates, there was a significant association between low serum bicarbonate and all-cause mortality (hazard ratio [HR] 1.23, 95% CI 1.16, 1.31). This association was not statistically significant among patients with stage 4 CKD and diabetes. The time-dependent analysis demonstrated a significant mortality risk associated with a decline from normal to low bicarbonate level (HR 1.59, 95% CI 1.49, 1.69). High serum bicarbonate levels were associated with death irrespective of the level of kidney function (HR 1.74, 95% CI 1.52, 2.00). When serum bicarbonate was examined as a continuous variable, a J-shaped relationship was noted between serum bicarbonate and mortality.

Conclusions: Low serum bicarbonate levels are associated with increased mortality among stage 3 CKD patients and patients without diabetes. High serum bicarbonate levels are associated with mortality in both stage 3 and stage 4 CKD patients.

Figure 1.

Flow chart showing how patients were selected for this analysis from the electronic-health-record-based registry. CKD, chronic kidney disease; eGFR, estimated GFR.

Figure 2.

Kaplan–Meier survival curve based on serum bicarbonate levels among chronic kidney disease patients.

Figure 3.

Associations (log hazard and 95% confidence interval) between all-cause mortality and baseline serum bicarbonate levels. Model adjusted for age, gender, African-American race, body mass index, diabetes, hypertension, hyperlipidemia, malignancy, congestive heart failure, cerebrovascular disease, and coronary artery disease at chronic kidney disease diagnosis and estimated GFR, use of renin-angiotensin system blockers and diuretics, hemoglobin and albumin.

Figure 4.

Hazard ratio and 95% confidence interval (CI) of all-cause mortality associated with low serum bicarbonate levels among select subgroups. eGFR, estimated GFR.