Abstract
INTRODUCTION: Low serum bicarbonate at a single point in time is associated with accelerated kidney decline in patients with chronic kidney disease (CKD). We modeled how changes in serum bicarbonate over time affect incidence of adverse kidney outcomes. METHODS: We analyzed data from Optum's deidentified Integrated Claims-Clinical data set of US patients (2007-2019) with ≥1 year of prior medical record data, CKD stages G3 to G5, and metabolic acidosis (i.e., index serum bicarbonate 12 to <22 mmol/l). The primary predictor of interest was the change in serum bicarbonate, evaluated at each postindex outpatient serum bicarbonate test as a time-dependent continuous variable. The primary outcome was a composite of either a ≥40% decline in estimated glomerular filtration rate (eGFR) from index or evidence of dialysis or transplantation, evaluated using Cox proportional hazards models. RESULTS: A total of 24,384 patients were included in the cohort with median follow-up of 3.7 years. A within-patient increase in serum bicarbonate over time was associated with a lower risk of the composite kidney outcome. The unadjusted hazard ratio (HR) per 1-mmol/l increase in serum bicarbonate was 0.911 (95% confidence interval [CI]: 0.905-0.917; P < 0.001). After adjustment for baseline eGFR and serum bicarbonate, the time-adjusted effect of baseline eGFR and other covariates, the HR per 1-mmol/l increase in serum bicarbonate was largely unchanged (0.916 [95% CI: 0.910-0.922; P < 0.001]). CONCLUSION: In a real-world population of US patients with CKD and metabolic acidosis, a within-patient increase in serum bicarbonate over time independent of changes in eGFR, was associated with a lower risk of CKD progression.