Busch Martin, Franke Sybille, Wolf Gunter, Brandstädt Antje, Ott Undine, Gerth Jens, Hunsicker Lawrence G, Stein Guenter
Department of Internal Medicine III and Institute of Medical Statistics and Computer Sciences, University of Jena, Germany.
Am J Kidney Dis. 2006 Oct;48(4):571-9. doi: 10.1053/j.ajkd.2006.07.009.
Advanced glycation end products (AGEs) are implicated in the pathogenesis of vascular damage, especially in patients with diabetes and renal insufficiency. The oxidatively formed AGE N(epsilon)-carboxymethyllysine (CML) is thought to be a marker of oxidative stress.
Four hundred fifty patients with type 2 diabetes and nephropathy from the Irbesartan in Diabetic Nephropathy Trial cohort (mean age, 58 +/- 8.2 years; 137 women, 313 men) with a mean glomerular filtration rate of 48.2 mL/min (0.80 mL/s; Modification of Diet in Renal Disease formula) were followed up for 2.6 years. Serum CML was measured by using an enzyme-linked immunosorbent assay. Relationships between CML levels, traditional risk factors, and cardiovascular and renal events were tested in Cox proportional hazards models.
Mean serum CML level was 599.9 +/- 276.0 ng/mL, and mean hemoglobin A1c level was 7.5% +/- 1.6%. One hundred forty-three first cardiovascular events occurred during follow-up; 74 patients died, 44 of cardiovascular causes. Final multivariate analysis showed age (relative risk [RR], 1.87; confidence interval [CI], 1.13 to 3.11; P = 0.016 for the highest compared with lowest quartile), history of prior cardiovascular events (RR, 1.96; CI, 1.35 to 2.85; P < 0.0005), and 24-hour urinary albumin-creatinine ratio (RR, 1.29; CI, 1.11 to 1.50 per doubling; P < 0.0005) to be independent risk factors for a first cardiovascular event, but not CML level. CML level also did not correlate significantly with renal outcome.
Serum CML level could not be identified as an independent risk factor for cardiovascular or renal outcomes in the examined population. This suggests that traditional risk factors might have a more important role for these end points or that other AGE compounds, as well as tissue AGE levels, might be of greater relevance compared with serum levels, which remains open to further study.
晚期糖基化终末产物（AGEs）与血管损伤的发病机制有关，尤其是在糖尿病和肾功能不全患者中。氧化形成的AGE N(ε)-羧甲基赖氨酸（CML）被认为是氧化应激的标志物。
对来自厄贝沙坦治疗糖尿病肾病试验队列的450例2型糖尿病肾病患者（平均年龄58±8.2岁；女性137例，男性313例）进行随访，平均肾小球滤过率为48.2 mL/min（0.80 mL/s；采用肾脏病饮食改良公式），随访时间为2.6年。采用酶联免疫吸附测定法检测血清CML。在Cox比例风险模型中测试CML水平、传统危险因素与心血管和肾脏事件之间的关系。
血清CML平均水平为599.9±276.0 ng/mL，糖化血红蛋白平均水平为7.5%±1.6%。随访期间发生143例首次心血管事件；74例患者死亡，其中44例死于心血管原因。最终多变量分析显示，年龄（相对风险[RR]，1.87；置信区间[CI]，1.13至3.11；最高四分位数与最低四分位数相比，P = 0.016）、既往心血管事件史（RR，1.96；CI，1.35至2.85；P < 0.0005）和24小时尿白蛋白肌酐比值（RR，1.29；CI，每增加一倍为1.11至1.50；P < 0.0005）是首次心血管事件的独立危险因素，但CML水平不是。CML水平与肾脏结局也无显著相关性。
在所研究人群中，血清CML水平不能被确定为心血管或肾脏结局的独立危险因素。这表明传统危险因素可能对这些终点起更重要的作用，或者与血清水平相比，其他AGE化合物以及组织AGE水平可能更具相关性，这仍有待进一步研究。
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