Lieuw-A-Fa Mariska L M, van Hinsbergh Victor W M, Teerlink Tom, Barto Rob, Twisk Jos, Stehouwer Coen D A, Schalkwijk Casper G
Department of Physiology, and Institute of Cardiovascular Research, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands.
Nephrol Dial Transplant. 2004 Mar;19(3):631-6. doi: 10.1093/ndt/gfg619.
Diabetic and non-diabetic patients with renal failure have an increased risk for cardiovascular disease, which may be the result of uraemic toxins, including advanced glycation end-products (AGEs). The aim of the study was to investigate the levels of well-characterized AGEs, N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL) in relation to kidney function and to study the relationship of these AGEs to endothelial function and inflammation in type 1 diabetic patients.
Plasma levels of CML and CEL were measured in 60 type 1 diabetic patients categorized as having normal glomerular filtration rate (GFR) (>80 ml/min, n = 31) or decreased GFR (<80 ml/min, n = 29) as estimated by the Cockcroft-Gault formula. To assess the relationship of these AGEs to endothelial function and inflammation, markers of endothelial function von Willebrand factor (vWf), soluble vascular cellular adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble thrombomodulin (sTM), tissue type-specific plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein (CRP), a marker of inflammatory activity, were determined by enzyme-linked immunosorbent assays.
Plasma levels of CML and CEL were increased in diabetic patients with decreased GFR as compared with patients with normal GFR [CML 4.9 (2-12.6) vs 2.9 (1.7-4.4) micromol/l, P<0.000; and CEL 1.7 (0.9-3.3) vs 1.2 (1.7-4.4) micromol/l, P = 0.004, respectively). Independently of the GFR, the plasma levels of CML and CEL were significantly associated with sVCAM-1, vWf and sTM.
Plasma levels of CML and CEL rise with deterioration of GFR. Furthermore, CML and CEL levels are associated with markers of endothelial activation independently of renal function. This suggests an involvement of these AGEs in the acceleration of cardiovascular complications in patients with renal impairment.
糖尿病和非糖尿病肾衰竭患者患心血管疾病的风险增加，这可能是尿毒症毒素所致，其中包括晚期糖基化终产物（AGEs）。本研究旨在调查特征明确的AGEs、Nε-（羧甲基）赖氨酸（CML）和Nε-（羧乙基）赖氨酸（CEL）水平与肾功能的关系，并研究这些AGEs与1型糖尿病患者内皮功能和炎症的关系。
采用Cockcroft-Gault公式估算，将60例1型糖尿病患者分为肾小球滤过率（GFR）正常（>80 ml/min，n = 31）或GFR降低（<80 ml/min，n = 29）两组，测量其血浆CML和CEL水平。为评估这些AGEs与内皮功能和炎症的关系，通过酶联免疫吸附测定法测定内皮功能标志物血管性血友病因子（vWf）、可溶性血管细胞黏附分子-1（sVCAM-1）、可溶性E-选择素（sE-选择素）、可溶性血栓调节蛋白（sTM）、组织型纤溶酶原激活剂（tPA）和纤溶酶原激活剂抑制剂-1（PAI-1），以及炎症活性标志物C反应蛋白（CRP）。
与GFR正常的患者相比，GFR降低的糖尿病患者血浆CML和CEL水平升高[CML分别为4.9（2 - 12.6）与2.9（1.7 - 4.4）μmol/l，P<0.000；CEL分别为1.7（0.9 - 3.3）与1.2（1.7 - 4.4）μmol/l，P = 0.004]。不考虑GFR，CML和CEL的血浆水平与sVCAM-1、vWf和sTM显著相关。
CML和CEL的血浆水平随GFR恶化而升高。此外，CML和CEL水平与内皮激活标志物相关，且独立于肾功能。这表明这些AGEs参与了肾功能损害患者心血管并发症的加速发展。
