Background: Management of chronic kidney disease (CKD) requires the management of risk factors, such as hypertension and albuminuria, that affect CKD progression. Identification of additional modifiable risk factors is necessary to develop new treatment strategies for CKD. We sought to quantify the association of metabolic acidosis with CKD progression and mortality in a large U.S. community-based cohort.
Methods: In this longitudinal, retrospective cohort study we identified non-dialysis-dependent patients with stage 3‒5 CKD from Optum's de-identified integrated electronic health records. We selected cohorts of patients with confirmed metabolic acidosis or normal serum bicarbonate levels based on 2 consecutive serum bicarbonate values: 12 to < 22 mEq/L or 22-29 mEq/L, respectively, 28‒365 days apart. The primary composite outcome was ≥ 40 % decline in estimated glomerular filtration rate (eGFR), renal replacement therapy (chronic dialysis or kidney transplant), or all-cause mortality (DD40). Secondary outcomes included each component of the composite outcome. Cox proportional hazards models were used for the DD40 outcome and secondary outcomes, while logistic regression models were used for the DD40 outcome at 2 years.
Results: A total of 51,558 patients qualified for the study. The unadjusted 2-year incidence of adverse renal and fatal outcomes was significantly worse among patients in the metabolic acidosis group vs. those who had normal serum bicarbonate levels: 48 % vs. 17 % for DD40, 10 % vs. 4 % for ≥ 40 % decline in eGFR, 20 % vs. 6 % for renal replacement therapy, and 31 % vs. 10 % for all-cause mortality (all P < 0.001). Over a ≤ 10-year period, for each 1-mEq/L increase in serum bicarbonate, the adjusted hazard ratio for DD40 was 0.926 (95 % confidence interval [CI], 0.922-0.930; P < 0.001); over a ≤ 2-year period, the adjusted odds ratio for DD40 was 0.873 (95 % CI, 0.866-0.879; P < 0.001).
Conclusions: In this large community cohort of patients with stage 3‒5 CKD, the presence of metabolic acidosis was a significant, independent risk factor for the composite adverse outcome of CKD progression, renal replacement therapy, and all-cause mortality (DD40).
Keywords: CKD progression; Chronic kidney disease; dialysis; metabolic acidosis; mortality; observational study; renal replacement therapy; serum bicarbonate; transplantation.