Metabolic Acidosis 1 Year Following Kidney Transplantation and Subsequent Cardiovascular Events and Mortality: An Observational Cohort Study.

Rationale & Objective: Recent studies suggest that metabolic acidosis is associated with mortality and graft failure in kidney transplant recipients. However, it is unknown whether serum bicarbonate (measured as total carbon dioxide [tCO ₂ ] in serum) levels predict cardiovascular events (CVEs) following kidney transplantation.
Study Design: Observational cohort study.
Settings & Participants: Single-center study of 2,128 kidney transplant recipients free of CVEs during the first 13.5 months following transplantation.
Predictor: tCO ₂ level at 1 year posttransplantation.
Outcomes: Ischemic, arrhythmic, and heart failure CVEs and death from any cause.
Analytical Approach: Independent associations were assessed using multivariable proportional hazards regression models. Restricted cubic spline Poisson models were used to explore nonlinear associations. Linear spline proportional hazards models were used to assess associations at different tCO ₂ levels.
Results: The prevalence of metabolic acidosis defined as tCO ₂ level < 24 mEq/L was 38.8% (n=826). There were 384 recipients with a CVE and 610 deaths during a median follow-up of 4.0 years. CVEs included 241 ischemic, 137 arrhythmic, and 150 heart failure events. tCO ₂  level < 20 mEq/L was associated with increased risk for CVEs (adjusted HR [aHR], 2.00; 95% CI, 1.29-3.10) compared to the reference category of tCO ₂ level of 24.0 to 25.9 mEq/L. This association was primarily due to ischemic CVEs (aHR, 2.28; 95% CI, 1.34-3.90). For every 1 mEq/L lower tCO ₂ level for those with tCO ₂ < 24 mEq/L, risks for all CVEs and ischemic events were 17% and 15% higher, respectively (aHR for all CVEs of 0.83 [95% CI, 0.74-0.94] and aHR for ischemic CVEs of 0.85 [95% CI, 0.74-0.99]). Notably, tCO ₂ level < 20 mEq/L, compared to tCO ₂ level of 24.0 to 25.9 mEq/L, was independently associated with all-cause mortality (aHR, 1.43; 95% CI, 1.02-2.02). For every 1-mEq/L lower tCO ₂ level for those with tCO ₂ < 24 mEq/L, there was 17% higher risk for death (aHR, 0.83; 95% CI, 0.75-0.92).
Limitations: Single-center observational study.
Conclusions: Metabolic acidosis is an independent risk factor for ischemic CVEs after kidney transplantation. It is unknown whether correction of acidosis improves outcomes in these patients.
(Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)