Abstract

BACKGROUND Advanced glycation endproducts (AGE) have been implicated in the pathogenesis of chronic transplant dysfunction and cardiovascular (CV) disease of renal transplant recipients (RTR), but no prospective studies have been performed to date. We investigated the association of plasma AGE levels with graft failure (GF) and CV mortality in a cohort of RTR with long-term follow-up. METHODS Tandem mass spectrometry was performed to simultaneously measure the AGE Nε-(Carboxymethyl)lysine (CML) and Nε-(Carboxyethyl)lysine (CEL) levels in hydrolysates of plasma proteins. Multivariate-adjusted Cox-proportional hazards regression analysis was used to assess prospective associations with clinical outcomes. RESULTS We included 555 RTR (mean (SD) age 51±12 years old, 56% males). During median follow-up for 6.9 [IQR, 6.2-7.2] years, 67 (12%) RTR developed GF, and 122 (22%) died (52% were due to CV causes). In analyses adjusted for potential confounders, including age, sex, estimated Glomerular Filtration Rate (eGFR) and proteinuria, CML levels were not independently associated with GF, but they were with CV mortality (Table 1). In similar analyses, CEL levels were independently associated with GF and CV mortality (Table 1). The association of CML levels with GF was modified by renal function (Pint<0.001), with a significant and independent association in RTR with eGFR≤45 mL/min/1.73m2 (HR, 1.75; 95% CI, 1.06-2.89; P=0.03). CONCLUSION High plasma levels of the AGE CML and CEL were independently associated with increased risk of GF and premature CV mortality. These results strengthen the quest for studying AGE-targeted interventions as potential therapeutic strategy to improve long-term outcomes in RTR.