Prasad Kailash, Dhar Indu, Zhou Qifeng, Elmoselhi Hamdi, Shoker Muhammad, Shoker Ahmed
Department of Physiology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, S7N 5E5, Canada.
Department of Medicine, College of Medicine and Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada.
Mol Cell Biochem. 2016 Dec;423(1-2):105-114. doi: 10.1007/s11010-016-2829-4. Epub 2016 Oct 6.
Interaction of advanced glycation end products (AGEs) with its cell-bound receptor (RAGE) results in cell dysfunction through activation of nuclear factor kappa-B, increase in expression and release of inflammatory cytokines, and generation of oxygen radicals. Circulating soluble receptors, soluble receptor (sRAGE), endogenous secretory receptor (esRAGE) and cleaved receptor (cRGAE) act as decoy for RAGE ligands and thus have cytoprotective effects. Low levels of sRAGE and esRAGE have been proposed as biomarkers for many diseases. However sRAGE and esRAGE levels are elevated in diabetes and chronic renal diseases and still tissue injury occurs. It is possible that increases in levels of AGEs are greater than increases in the levels of soluble receptors in these two diseases. Some new parameters have to be used which could be an universal biomarkers for cell dysfunction. It is hypothesized that increases in serum levels of AGEs are greater than the increases in the soluble receptors, and that the levels of AGEs is correlated with soluble receptors and that the ratios of AGEs/sRAGE, AGEs/esRAGE and AGEs/cRAGE are elevated in patients with end-stage renal disease (ESRD) and would serve as an universal risk marker for ESRD. The study subject comprised of 88 patients with ESRD and 20 healthy controls. AGEs, sRAGE and esRAGE were measured using commercially available enzyme linked immune assay kits. cRAGE was calculated by subtracting esRAGE from sRAGE. The data show that the serum levels of AGEs, sRAGE, cRAGE are elevated and that the elevation of AGEs was greater than those of soluble receptors. The ratios of AGEs/sRAGE, AGEs/esRAGE and AGEs/cRAGE were elevated and the elevation was similar in AGEs/sRAGE and AGEs/cRAGE but greater than AGEs/esRAGE. The sensitivity, specificity, accuracy, and positive and negative predictive value of AGEs/sRAGE and AGEs/cRAGE were 86.36 and 84.88 %, 86.36 and 80.95 %, 0.98 and 0.905, 96.2 and 94.8 %, and 61.29 and 56.67 % respectively. There was a positive correlation of sRAGE with esRAGE and cRAGE, and AGEs with esRAGE; and negative correlation between sRAGE and AGEs/sRAGE, esRAGE and AGES/esRAGE, and cRAGE and AGES/cRAGE. In conclusion, AGEs/sRAGE, AGEs/cRAGE and AGEs/esRAGE may serve as universal risk biomarkers for ESRD and that AGEs/sRAGE and AGEs/cRAGE are better risk biomarkers than AGEs/esRAGE.
晚期糖基化终末产物（AGEs）与其细胞表面受体（RAGE）相互作用，通过激活核因子κB、增加炎性细胞因子的表达和释放以及产生活性氧，导致细胞功能障碍。循环中的可溶性受体，即可溶性受体（sRAGE）、内源性分泌受体（esRAGE）和裂解受体（cRGAE），可作为RAGE配体的诱饵，因此具有细胞保护作用。低水平的sRAGE和esRAGE已被提议作为多种疾病的生物标志物。然而，在糖尿病和慢性肾脏疾病中，sRAGE和esRAGE水平升高，但仍会发生组织损伤。在这两种疾病中，AGEs水平的升高可能大于可溶性受体水平的升高。必须使用一些新的参数，这些参数可能是细胞功能障碍的通用生物标志物。据推测，血清AGEs水平的升高大于可溶性受体的升高，并且AGEs水平与可溶性受体相关，并且在终末期肾病（ESRD）患者中，AGEs/sRAGE、AGEs/esRAGE和AGEs/cRAGE的比值升高，将作为ESRD的通用风险标志物。研究对象包括88例ESRD患者和20名健康对照。使用市售的酶联免疫分析试剂盒测量AGEs、sRAGE和esRAGE。cRAGE通过从sRAGE中减去esRAGE来计算。数据显示，血清AGEs、sRAGE、cRAGE水平升高，且AGEs的升高大于可溶性受体。AGEs/sRAGE、AGEs/esRAGE和AGEs/cRAGE的比值升高，AGEs/sRAGE和AGEs/cRAGE的升高相似，但大于AGEs/esRAGE。AGEs/sRAGE和AGEs/cRAGE的敏感性、特异性、准确性以及阳性和阴性预测值分别为86.36%和84.88%、86.36%和80.95%、0.98和0.905、96.2%和94.8%、61.29%和56.67%。sRAGE与esRAGE和cRAGE、AGEs与esRAGE呈正相关；sRAGE与AGEs/sRAGE、esRAGE与AGES/esRAGE、cRAGE与AGES/cRAGE呈负相关。总之，AGEs/sRAGE、AGEs/cRAGE和AGEs/esRAGE可能作为ESRD的通用风险生物标志物，并且AGEs/sRAGE和AGEs/cRAGE比AGEs/esRAGE是更好的风险生物标志物。
