Potential cardiovascular risk factors in chronic kidney disease:: AGEs, total homocysteine and metabolites, and the C-reactive protein
Potential cardiovascular risk factors in chronic kidney disease:: AGEs, total homocysteine and metabolites, and the C-reactive protein
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DOI：
10.1111/j.1523-1755.2004.00736.x
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发表时间：
2004-07-01
影响因子：
19.6
通讯作者：
Stein, G
中科院分区：
文献类型：
--
作者：
Busch, M;Franke, S;Stein, G
背景总同型半胱氨酸（tHcy）和晚期糖基化终产物（AGEs）参与血管损伤的发病机制。本研究旨在探讨血清AGEs戊糖苷、N-羟-羧甲基赖氨酸（CML）和咪唑酮、tHcy、胱硫醚、甲基丙二酸（MMA）和2-甲基柠檬酸（2-MCA）以及C反应蛋白（CRP）水平升高是否与心血管事件的高风险相关。共对232例慢性肾脏疾病患者（平均年龄57.6 ± 13.1岁，82例女性和150例男性）、99例慢性肾功能衰竭（CRF）患者、84例维持性血液透析患者和49例肾移植受者进行了为期2年的随访。采用考克斯比例风险模型对所有受试者的相关参数、常规危险因素和CRP水平升高与心血管事件之间的关系进行检验。与健康受试者相比，发现所有三组中AGEs、tHcy和代谢产物的平均血清水平均显著升高（分别为P < 0.01）。随访期间发生53例心血管事件，共40例患者死亡。最终的多变量分析显示糖尿病（RR 2.06，95% CI 1.17-3.60，P = 0.013），终末期肾病（ESRD）CRP水平升高（RR 2.00，95%CI 1.11-3.60，P = 0.021）是心血管事件的独立危险因素。来自CRF患者、接受维持性血液透析治疗的患者和肾移植受者的数据提供了证据，表明传统风险因素（如糖尿病、ESRD的存在以及所考虑的风险因素CRP水平升高）似乎比AGEs、tHcy和相关代谢物水平升高对慢性肾脏疾病患者的心血管结局起更重要的作用。有证据表明，在慢性肾功能不全的情况下，可以推荐常规CRP测量。
Background. Total homocysteine (tHcy) and advanced glycation end-products (AGEs) are implicated in the pathogenesis of vascular damage. This study aimed to investigate whether elevated serum levels of the AGEs pentosidine, N-epsilon-carboxymethyllysine (CML) and imidazolone; tHcy, cystathionine, methylmalonic acid (MMA), and 2-methylcitric acid (2-MCA), as well as C-reactive protein (CRP), are related to a higher risk for cardiovascular events.Methods. A total of 232 patients with chronic kidney diseases (mean age 57.6 +/- 13.1 years, 82 female and 150 male); 99 with chronic renal failure (CRF), 84 maintenance hemodialysis patients and 49 renal transplant recipients were followed for 2 years. The relationship between the parameters of interest, conventional risk factors and elevated levels of CRP with cardiovascular events was tested in all subjects by the Cox proportional hazards model.Results. Mean serum levels of AGEs, tHcy, and of the metabolites were found to be significantly increased in all three groups compared to the healthy subjects (P < 0.01, respectively). Fifty-three cardiovascular events occurred during follow-up; a total of 40 patients died. Final multivariate analysis showed diabetes (RR 2.06, 95% CI 1.17-3.60, P = 0.013), end-stage renal disease (ESRD) (RR 4.88, 95% CI 2.40-9.89, P < 0.001) and elevated CRP levels (RR 2.00, 95% CI 1.11-3.60, P = 0.021) as independent risk factors for cardiovascular events.Conclusion. Data from a group consisting of patients with CRF, patients undergoing maintenance hemodialysis treatment, and renal transplant recipients provide evidence that conventional risk factors such as the presence of diabetes, ESRD, as well as elevated levels of the considered risk factor CRP, seem to play a more important role for cardiovascular outcome in patients with chronic kidney disease than elevated levels of AGEs, tHcy, and related metabolites. The evidence suggests that routine CRP measurement can be recommended in cases of chronic renal insufficiency.