Circulating Advanced Glycation Endproducts and Long-Term Risk of Cardiovascular Mortality in Kidney Transplant Recipients

Camilo G. Sotomayor*, Antonio W. Gomes-Neto, Marco van Londen, Rijk O. B. Gans, Ilja M. Nolte, Stefan P. Berger, Gerjan J. Navis, Ramon Rodrigo, Henri G. D. Leuvenink, Casper G. Schalkwijk, Stephan J. L. Bakker

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background and objectives In kidney transplant recipients, elevated circulating advanced glycation endproducts (AGEs) are the result of increased formation and decreased kidney clearance. AGEs trigger several intracellular mechanisms that ultimately yield excess cardiovascular disease. We hypothesized that, in stable kidney transplant recipients, circulating AGEs are associated with long-term risk of cardiovascular mortality, and that such a relationship is mediated by inflammatory, oxidative stress, and endothelial dysfunction biomarkers.

Design, setting, participants, & measurements Prospective cohort study of stable kidney transplant recipients recruited between 2001 and 2003 in a university setting. We performed multivariable-adjusted Cox regression analyses to assess the association of AGEs (i.e., N-epsilon-[Carboxymethyl]lysine (CML) and N-epsilon-[Carboxyethyl]lysine (CEL), measured by tandem mass spectrometry) with cardiovascular mortality. Mediation analyses were performed according to Preacher and Hayes's procedure.

Results We included 555 kidney transplant recipients (age 51-12 years, 56% men). During a median follow-up of 6.9 years, 122 kidney transplant recipients died (52% deaths were due to cardiovascular causes). CML and CEL concentrations were directly associated with cardiovascular mortality (respectively, hazard ratio, 1.55; 95% confidence interval, 1.24 to 1.95; P

Conclusions In stable kidney transplant recipients, circulating levels of AGEs are independently associated with long- term risk of cardiovascular mortality.

Original languageEnglish
Pages (from-to)1512-1520
Number of pages9
JournalClinical journal of the American Society of Nephrology
Volume14
Issue number10
DOIs
Publication statusPublished - 7 Oct 2019

Keywords

  • advanced glycation end-product
  • cardiovascular mortality
  • renal transplantation
  • oxidative stress
  • endothelial dysfunction
  • humans
  • area under curve
  • ROC curve
  • Glycation End Products
  • Advanced
  • confidence interval
  • Transplantation
  • Homologous
  • kidney transplantation
  • allografts
  • kidney diseases
  • kidney disease
  • fibrosis
  • biopsy
  • kidney biopsy
  • magnetic resonance imaging
  • hypoxia
  • glomerulonephritis
  • oxygen
  • cardiovascular disease
  • cohort studies
  • END-PRODUCTS
  • N-EPSILON-(CARBOXYMETHYL) LYSINE
  • ENDOTHELIAL DYSFUNCTION
  • PREDICTS MORTALITY
  • OXIDANT STRESS
  • ACCUMULATION
  • INFLAMMATION
  • CREATININE
  • SURVIVAL
  • DISEASE

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