Peppa Melpomeni, Uribarri Jaime, Cai Weijing, Lu Min, Vlassara Helen
Department of Geriatrics, Division of Experimental Diabetes and Aging, Mount Sinai School of Medicine, New York, NY 10029, USA.
Am J Kidney Dis. 2004 Apr;43(4):690-5. doi: 10.1053/j.ajkd.2003.11.022.
Inflammation is common in patients with chronic renal failure and has been associated with the increased risk for cardiovascular disease (CVD) in this condition. Advanced glycoxidation end products (AGEs) are among the factors implicated in the inflammatory state of chronic renal failure.
In a cross-sectional study of 189 dialysis patients, we measured circulating levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), vascular adhesion molecule-1 (VCAM-1), vascular endothelial growth factor (VEGF), and plasminogen activator inhibitor-1 (PAI-1) to test for possible relationships between them and serum AGE levels. In addition, these parameters were measured in a subgroup of 18 patients with chronic renal failure randomly assigned to a 4-week diet, either low (L-AGE) or high (H-AGE) in AGE content. AGEs were measured by means of a monoclonal antibody against epsilonN-carboxymethyllysine.
At baseline, serum AGE levels, as well as those for CRP, TNF-alpha, VCAM-1, and VEGF, were markedly elevated, although no correlation was found between AGE levels and the other markers. Dietary AGE modulation resulted in a significant decrease in levels of serum AGEs, CRP, and PAI-1 in the L-AGE group (approximately 35%, 44%, and 17%, respectively; P < 0.03), whereas only serum AGE levels increased significantly in the H-AGE group. VCAM-1 and TNF-alpha levels, although similar at baseline, became significantly lower in patients on an L-AGE compared with H-AGE diet (P < 0.05) at the end of the study.
Data from the interventional phase of the study suggest that AGEs have a role in the initiation of the inflammatory state of chronic renal failure, which eventually leads to increased CVD. This finding opens the possibility for using anti-AGE strategies in the prevention and treatment of CVD in patients with chronic renal failure.
炎症在慢性肾衰竭患者中很常见，并且与该疾病中心血管疾病（CVD）风险增加有关。晚期糖基化终末产物（AGEs）是与慢性肾衰竭炎症状态相关的因素之一。
在一项对189名透析患者的横断面研究中，我们测量了循环中的C反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）、血管黏附分子-1（VCAM-1）、血管内皮生长因子（VEGF）和纤溶酶原激活物抑制剂-1（PAI-1）水平，以检测它们与血清AGE水平之间的可能关系。此外，在一个由18名慢性肾衰竭患者组成的亚组中测量了这些参数，这些患者被随机分配到一种为期4周的饮食中，饮食中的AGE含量要么低（L-AGE）要么高（H-AGE）。通过针对εN-羧甲基赖氨酸的单克隆抗体测量AGEs。
在基线时，血清AGE水平以及CRP、TNF-α、VCAM-1和VEGF水平均显著升高，尽管未发现AGE水平与其他标志物之间存在相关性。饮食AGE调节导致L-AGE组的血清AGEs、CRP和PAI-1水平显著降低（分别约为35%、44%和17%；P<0.03），而H-AGE组中只有血清AGE水平显著升高。在研究结束时，与H-AGE饮食相比，L-AGE饮食患者的VCAM-1和TNF-α水平虽然在基线时相似，但显著降低（P<0.05）。
该研究干预阶段的数据表明，AGEs在慢性肾衰竭炎症状态的起始中起作用，这最终导致CVD增加。这一发现为在慢性肾衰竭患者的CVD预防和治疗中使用抗AGE策略开辟了可能性。
