Metabolic Acidosis 1 Year Following Kidney Transplantation and Subsequent Cardiovascular Events and Mortality

An Observational Cohort Study

Arjang Djamali, Tripti Singh, Michal L. Melamed, James H. Stein, Fahad Aziz, Sandesh Parajuli, Maha Mohamed, Neetika Garg, Didier Mandelbrot, Donald E. Wesson, Brad C. Astor

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 [tCO2] 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: tCO2 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 tCO2 levels. Results: The prevalence of metabolic acidosis defined as tCO2 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. tCO2 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 tCO2 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 tCO2 level for those with tCO2 < 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, tCO2 level < 20 mEq/L, compared to tCO2 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 tCO2 level for those with tCO2 < 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.

Original languageEnglish (US)
JournalAmerican Journal of Kidney Diseases
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Acidosis
Kidney Transplantation
Observational Studies
Cohort Studies
Mortality
Proportional Hazards Models
dioxotechnetium
Heart Failure
Bicarbonates
Serum
Carbon Dioxide
Renal Insufficiency
Cause of Death
Transplantation
Transplants
Kidney

Keywords

  • arrhythmia
  • cardiovascular events (CVE)
  • coronary artery disease
  • heart failure
  • hypobicarbonatemia
  • kidney transplantation
  • Metabolic acidosis
  • mortality
  • myocardial infarction
  • serum bicarbonate
  • total CO

ASJC Scopus subject areas

  • Nephrology

Cite this

Metabolic Acidosis 1 Year Following Kidney Transplantation and Subsequent Cardiovascular Events and Mortality : An Observational Cohort Study. / Djamali, Arjang; Singh, Tripti; Melamed, Michal L.; Stein, James H.; Aziz, Fahad; Parajuli, Sandesh; Mohamed, Maha; Garg, Neetika; Mandelbrot, Didier; Wesson, Donald E.; Astor, Brad C.

In: American Journal of Kidney Diseases, 01.01.2019.

Research output: Contribution to journalArticle

Djamali, Arjang ; Singh, Tripti ; Melamed, Michal L. ; Stein, James H. ; Aziz, Fahad ; Parajuli, Sandesh ; Mohamed, Maha ; Garg, Neetika ; Mandelbrot, Didier ; Wesson, Donald E. ; Astor, Brad C. / Metabolic Acidosis 1 Year Following Kidney Transplantation and Subsequent Cardiovascular Events and Mortality : An Observational Cohort Study. In: American Journal of Kidney Diseases. 2019.
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title = "Metabolic Acidosis 1 Year Following Kidney Transplantation and Subsequent Cardiovascular Events and Mortality: An Observational Cohort Study",
abstract = "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 [tCO2] 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: tCO2 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 tCO2 levels. Results: The prevalence of metabolic acidosis defined as tCO2 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. tCO2 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 tCO2 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 tCO2 level for those with tCO2 < 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, tCO2 level < 20 mEq/L, compared to tCO2 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 tCO2 level for those with tCO2 < 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.",
keywords = "arrhythmia, cardiovascular events (CVE), coronary artery disease, heart failure, hypobicarbonatemia, kidney transplantation, Metabolic acidosis, mortality, myocardial infarction, serum bicarbonate, total CO",
author = "Arjang Djamali and Tripti Singh and Melamed, {Michal L.} and Stein, {James H.} and Fahad Aziz and Sandesh Parajuli and Maha Mohamed and Neetika Garg and Didier Mandelbrot and Wesson, {Donald E.} and Astor, {Brad C.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1053/j.ajkd.2018.12.023",
language = "English (US)",
journal = "American Journal of Kidney Diseases",
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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.

PY - 2019/1/1

Y1 - 2019/1/1

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 [tCO2] 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: tCO2 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 tCO2 levels. Results: The prevalence of metabolic acidosis defined as tCO2 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. tCO2 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 tCO2 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 tCO2 level for those with tCO2 < 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, tCO2 level < 20 mEq/L, compared to tCO2 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 tCO2 level for those with tCO2 < 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 [tCO2] 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: tCO2 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 tCO2 levels. Results: The prevalence of metabolic acidosis defined as tCO2 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. tCO2 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 tCO2 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 tCO2 level for those with tCO2 < 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, tCO2 level < 20 mEq/L, compared to tCO2 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 tCO2 level for those with tCO2 < 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 - arrhythmia

KW - cardiovascular events (CVE)

KW - coronary artery disease

KW - heart failure

KW - hypobicarbonatemia

KW - kidney transplantation

KW - Metabolic acidosis

KW - mortality

KW - myocardial infarction

KW - serum bicarbonate

KW - total CO

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