Wada T, Miyata T, Kurokawa K
Institute of Medical Sciences and Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Nephrol Dial Transplant. 1999;14 Suppl 1:79-81. doi: 10.1093/ndt/14.suppl_1.79.
Advanced glycation end products (AGEs) are formed during non-enzymatic glycation and oxidation (glycoxidation) reactions. AGEs, such as pentosidine and carboxymethyllysine are increased in plasma proteins and skin collagen of uraemic patients several times more than in normal subjects and non-uraemic diabetic patients. However, AGEs do not differ between diabetics and non-diabetics in uraemic patients. The AGE accumulation in uraemia, therefore, cannot be attributed to hyperglycaemia, nor simply to a decreased removal by glomerular filtration of AGE-modified proteins. Recent evidence has suggested that, in uraemia, the increased carbonyl compounds, derived from both carbohydrates and lipids, modify proteins not only by glycoxidation but also by lipoxidation reactions, leading to the increased production of AGEs and advanced lipoxidation end products (ALEs). Thus, uraemia might be a state of increased carbonyl compounds with potentially damaging proteins ('carbonyl stress'). Carbonyl stress in uraemia appears relevant to long-term complications, such as dialysis-related amyloidosis. The increased AGEs and ALEs in uraemic plasma and tissue proteins may indicate alterations in the non-enzymatic chemistry involving both carbohydrates and lipids in uraemia.
晚期糖基化终末产物（AGEs）在非酶糖基化和氧化（糖氧化）反应过程中形成。诸如戊糖苷和羧甲基赖氨酸等AGEs在尿毒症患者的血浆蛋白和皮肤胶原蛋白中的含量比正常受试者和非尿毒症糖尿病患者高出数倍。然而，在尿毒症患者中，糖尿病患者和非糖尿病患者之间的AGEs并无差异。因此，尿毒症中AGEs的积累既不能归因于高血糖，也不能简单地归因于肾小球滤过对AGE修饰蛋白清除的减少。最近的证据表明，在尿毒症中，源自碳水化合物和脂质的羰基化合物增加，不仅通过糖氧化，还通过脂氧化反应修饰蛋白质，导致AGEs和晚期脂氧化终末产物（ALEs）的产生增加。因此，尿毒症可能是一种羰基化合物增加且可能损害蛋白质的状态（“羰基应激”）。尿毒症中的羰基应激似乎与长期并发症有关，如透析相关淀粉样变。尿毒症血浆和组织蛋白中AGEs和ALEs的增加可能表明尿毒症中涉及碳水化合物和脂质的非酶化学发生了改变。
