Supplementary Material for: Serum and Tissue Levels of Advanced Glycation End Products and Risk of Mortality in Patients on Maintenance Hemodialysis

Background: The relation of tissue and circulating advanced glycation end products (AGEs) with mortality in hemodialysis (HD) patients remains inconclusive. We aimed to investigate the association of serum AGEs (CML) and tissue AGEs estimated by skin autofluorescence (SAF) with all-cause and cardiovascular disease (CVD) mortality, and examine the possible modifiers for the association in HD patients with by far the largest sample size in any similar studies. Methods: A total of 1,634 HD patients were included from the China Cooperative Study on Dialysis (CCSD), a multicenter prospective cohort study. The primary and secondary outcomes were all-cause mortality and CVD mortality, respectively. Results: The median follow-up duration was 5.2 years. Overall, there was a positive relation of baseline SAF levels with the risk of all-cause mortality (per 1 AU increment, adjusted hazard ratio (HR), 1.30; 95% confidence interval (CI): 1.12, 1.50) and CVD mortality (per 1 AU increment, adjusted HR, 1.36; 95% CI: 1.14, 1.62). Moreover, a stronger positive association between baseline SAF (per 1 AU increment) and all-cause mortality was found in participants with shorter dialysis vintage, or lower C-reactive protein levels (Both p interactions Conclusions: In patients undergoing long-term HD, baseline SAF, but not serum CML, was significantly associated with the risk of all-cause and CVD death.背景：组织与循环中晚期糖基化终末产物（advanced glycation end products, AGEs）与血液透析（hemodialysis, HD）患者死亡率的关联迄今尚无定论。本研究旨在探讨血清晚期糖基化终末产物（CML）及通过皮肤自体荧光（skin autofluorescence, SAF）评估的组织晚期糖基化终末产物水平与全因死亡率、心血管疾病（cardiovascular disease, CVD）死亡率的关联，并在同类研究中样本量最大的血液透析患者队列中，分析该关联可能的调节因素。方法：本研究数据来自多中心前瞻性队列研究——中国透析合作研究（China Cooperative Study on Dialysis, CCSD），共纳入1634名血液透析患者。研究的主要结局为全因死亡率，次要结局为心血管疾病死亡率。结果：中位随访时长为5.2年。整体而言，基线皮肤自体荧光水平与全因死亡率风险呈正相关（每增加1AU，调整后风险比（hazard ratio, HR）为1.30；95%置信区间（confidence interval, CI）：1.12~1.50），与心血管疾病死亡率风险亦呈正相关（每增加1AU，调整后HR为1.36；95%CI：1.14~1.62）。此外，在透析龄较短或C反应蛋白水平较低的受试者中，基线皮肤自体荧光水平（每增加1AU）与全因死亡率间的正向关联更为显著（两项交互检验P值均）。结论：在长期接受血液透析的患者中，基线皮肤自体荧光水平与全因死亡及心血管疾病死亡风险显著相关，而血清CML则无此关联。