Relationship between serum advanced glycation end products and endothelial dysfunction and low-grade inflammation in patients with end-stage renal disease during a transition into renal replacement therapy

Objective  To explore the relationship between serum advanced glycation end products（AGEs）, endothelial dysfunction（ED） and low-grade inflammation（LGI） in patients with end-stage renal disease（ESRD） during a transition into renal replacement therapy.

Methods  For this cross-sectional observational study, clinical data were reviewed for chronic kidney disease stage 5 non-dialysis（CKD5-ND） patients scheduled for dialysis or renal transplantation from February 2016 to July 2021. In addition, 50 health checkups were included as controls. Serum levels of free and protein-bound AGEs were measured by ultra-high performance liquid chromatography（UPLC） tandem mass spectrometry（MS）. N^ε-（carboxymethyl） lysine（CML）, N^ε-（carboxyethyl） lysine（CEL）, N^δ-（5-hydro-5-methyl-4-imidazolon-2-yl） ornithine （MG-H1） and tissue AGEs accumulation were evaluated by skin autofluorescence（SAF）. In addition, serum ED and LGI biomarkers were detected.

Results  Serum levels of free CML, protein binding CML, free CEL, protein binding CEL, free MG-H1 and protein binding MG-H1 in all CKD5-ND patients were 1142.2（765.1, 1538.3） nmol/L, 197.3（163.1, 256.6） nmol, 734.7（520.2, 939.4） nmol/L, 58.0（41.8, 74.3） nmol, 2244.4（1670.2, 3154.6） nmol/L and 59.1（47.6, 69.9） nmol. All parameters were higher than those in control group（P＜0.05）. In unadjusted analyses, high levels of serum free CML were associated with higher ED/LGI composite scores（P＜0.05）. Similarly, high levels of serum free CEL and protein-bound MG-H1 were associated with higher LGI composite scores（P＜0.05）. However, after adjusting for age, gender, treatment history and disease history, only serum free CML was an independent risk factor affecting the comprehensive ED score（P＜0.05）. After further adjustment for estimate glomerular filtration rate of the chronic kidney disease epidemiology collaboration, serum free CML was not associated with LGI composite score（P = 0.166）.

Conclusion  After adjusting for age, gender, treatment history and disease history, elevated serum AGE level is associated with ED/LGI in CKD5-ND patients. However, after adjusting for eGFR, this correlation become weaker, suggesting that eGFR confounding and/or adjusting for the relationship between serum AGEs and ED/LGI.