TY - JOUR
T1 - Metabolic Acidosis 1 Year Following Kidney Transplantation and Subsequent Cardiovascular Events and Mortality
T2 - An Observational Cohort Study
AU - Djamali, Arjang
AU - Singh, Tripti
AU - Melamed, Michal L.
AU - Stein, James H.
AU - Aziz, Fahad
AU - Parajuli, Sandesh
AU - Mohamed, Maha
AU - Garg, Neetika
AU - Mandelbrot, Didier
AU - Wesson, Donald E.
AU - Astor, Brad C.
N1 - Funding Information:
Arjang Djamali, MD, Tripti Singh, MD, Michal L. Melamed, MD, James H. Stein, MD, Fahad Aziz, MD, Sandesh Parajuli, MD, Maha Mohamed, MD, Neetika Garg, MD, Didier Mandelbrot, MD, Donald E. Wesson, MD, and Brad C. Astor, PhD. Research idea and study design: AD, MLM, BA, DEW, JHS; data acquisition: AD, SP, FA, MLM, NG, TS, DM; data analysis/interpretation: AD, BA; statistical analysis: BCA. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. No specific support. The authors declare that they have no relevant financial interests. Received April 19, 2018. Evaluated by 3 external peer reviewers, with direct editorial input from a Statistics/Methods Editor, an Associate Editor, and the Editor-in-Chief. Accepted in revised form December 2, 2018.
Publisher Copyright:
© 2019 National Kidney Foundation, Inc.
PY - 2019/4
Y1 - 2019/4
N2 - 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.
AB - 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.
KW - Metabolic acidosis
KW - arrhythmia
KW - cardiovascular events (CVE)
KW - coronary artery disease
KW - heart failure
KW - hypobicarbonatemia
KW - kidney transplantation
KW - mortality
KW - myocardial infarction
KW - serum bicarbonate
KW - total CO
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U2 - 10.1053/j.ajkd.2018.12.023
DO - 10.1053/j.ajkd.2018.12.023
M3 - Article
C2 - 30704880
AN - SCOPUS:85060520259
SN - 0272-6386
VL - 73
SP - 476
EP - 485
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 4
ER -