Serum Bicarbonate and Graft and Patient Outcomes Among Kidney Transplant Recipients: A Retrospective Cohort Study Evaluating Changes in Serum Bicarbonate Over Time

RATIONALE & OBJECTIVE: Identification of treatable risk factors for kidney allograft failure is necessary to improve graft longevity. Metabolic acidosis with either low serum bicarbonate or normal serum bicarbonate (eubicarbonatemic metabolic acidosis) is implicated in native kidney disease progression but its effects in kidney transplant recipients are unclear. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: An Integrated Claims-Clinical dataset of US patients with chronic kidney disease (estimated glomerular filtration rates <60 mL/min/1.73 m(2)) and serum bicarbonate data were used to generate a cohort of kidney transplant recipients with data from ≥1 year before and after transplantation. PRIMARY PREDICTOR: The primary independent variable was a change in serum bicarbonate from baseline. OUTCOMES: The primary outcomes were graft failure and all-cause mortality. The secondary outcomes were major adverse cardiac events and all-cause hospitalization. ANALYTICAL APPROACH: We used adjusted time-dependent Cox proportional hazards models to assess the risk of graft failure, all-cause mortality, major adverse cardiac events, and time to first hospitalization. RESULTS: In this US community-based cohort of 1,915 kidney transplant recipients with a median follow-up of ∼2.5 years, each 1-mEq/L increase in serum bicarbonate was associated with significantly lower hazard of graft loss, death, major adverse cardiac events, and hospitalization by 10%, 8%, 4%, and 8%, respectively. LIMITATIONS: Possible residual confounding. CONCLUSIONS: In a US community-based population of kidney transplant recipients, even small incremental increases in serum bicarbonate (1 mEq/L) were significantly associated with reduced hazard of graft loss, all-cause mortality, cardiovascular events, and hospitalization. Interventional trials evaluating the potential benefits of treating metabolic acidosis in kidney transplant recipients are warranted.