Association of serum bicarbonate levels with mortality in patients with non-dialysis-dependent CKD

Abstract

Background: Metabolic acidosis, usually manifested by low serum bicarbonate level, is common in chronic kidney disease (CKD) and appears to be associated with higher mortality in dialysis patients. It is not known whether a similar association is present in patients with non-dialysis-dependent CKD (NDD-CKD).

Methods: We used multivariable-adjusted Cox models to examine the association between baseline and time-variable serum bicarbonate (measured as total CO2) with the outcomes of all-cause mortality and the composite of pre-dialysis mortality or end-stage renal disease in 1240 male patients with moderate and advanced NDD-CKD.

Results: Serum bicarbonate showed a significant U-shaped association with all-cause mortality, with the highest mortality rate observed in patients with baseline serum bicarbonate levels <22 mmol/L [multivariable-adjusted hazard ratio (95% confidence interval) for patients with serum bicarbonate <22 mmol/L versus > or =22 mmol/L: 1.33 (1.05-1.69), P = 0.02] and the lowest mortality observed in patients with baseline serum bicarbonate of 26-29 mmol/L. The associations between lower serum bicarbonate level and mortality were more accentuated in subgroups of patients with better nutritional status and lower inflammation.

Conclusions: Both lower and higher serum bicarbonates are associated with increased all-cause mortality in patients with moderate and advanced NDD-CKD. Clinical trials are needed to determine if therapeutic interventions aimed at optimizing serum bicarbonate can result in improved outcomes in this population.

Fig. 1

Multivariable-adjusted log hazards ratios (95% confidence intervals) of all-cause mortality associated with baseline levels of serum bicarbonate in a fixed-covariate Cox model adjusted for age, race, body mass index, comorbidity index, diabetes mellitus, cardiovascular disease, smoking, systolic blood pressure, estimated glomerular filtration rate, serum phosphorus and albumin, white blood cell count, percentage of lymphocytes and use of medications.

Fig. 2

Multivariable-adjusted hazards ratios (95% confidence intervals) of all-cause mortality associated with a baseline serum bicarbonate of <22 mmol/L (versus ≥22 mmol/L) in select subgroups of patients.

Fig. 3

Multivariable-adjusted log hazards ratios (95% confidence intervals) of all-cause mortality associated with levels of serum bicarbonate in a time-dependent Cox model adjusted for age, race, diabetes mellitus, cardiovascular disease, body mass index, systolic blood pressure, estimated glomerular filtration rate, serum phosphorus and albumin, white blood cell count, percentage of lymphocytes and use of medications.

Fig. 4

Multivariable-adjusted log hazards ratios (95% confidence intervals) of the composite outcome of pre-dialysis mortality or end-stage renal disease associated with baseline levels of serum bicarbonate in a fixed-covariate Cox model adjusted for age, race, body mass index, comorbidity index, diabetes mellitus, cardiovascular disease, systolic blood pressure, proteinuria, estimated glomerular filtration rate, serum phosphorus and albumin, white blood cell count, percentage of lymphocytes and use of medications.