Kalousová Marta, Jáchymová Marie, Mestek Oto, Hodková Magdaléna, Kazderová Markéta, Tesar Vladimír, Zima Tomás
Institute of Clinical Chemistry and Laboratory Diagnostics, Department of Nephrology, 1st Faculty of Medicine and General University Hospital, Charles University, Karlovo nám. 32, 121 11 Prague 2, Czech Republic.
Nephrol Dial Transplant. 2007 Jul;22(7):2020-6. doi: 10.1093/ndt/gfm050. Epub 2007 Mar 8.
The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of vascular and inflammatory diseases. The pathological effects mediated via RAGE are physiologically inhibited by soluble RAGE (sRAGE). Our aim was to study sRAGE and RAGE gene polymorphisms in haemodialysis (HD) patients.
A total of 261 stable HD patients were enrolled in the study and prospectively followed up for 30 months. At the begining of the study, sRAGE inflammatory and nutritional parameters were determined. RAGE polymorphisms were determined in a subgroup of 214 HD patients. A group of 100 healthy controls was used for comparison.
In HD patients, sRAGE is elevated in comparison with healthy controls (3427+/-1508 vs 1758+/-637 pg/ml, P<0.001). It correlates negatively with residual diuresis (r=-0.193, P<0.05), with the acute phase reactants fibrinogen (r=-0.174, P<0.05) and orosomucoid (r=-0.135, P<0.05) and with the leucocyte count (r=-0.158, P<0.05). On the other hand, it is not related to the presence of diabetes mellitus, cardiovascular disease, nutritional status and mortality. The highest sRAGE levels are found in -429 CC and 2184 GG polymorphisms of the RAGE gene. The same results as for sRAGE were obtained for endogenous secretory RAGE (esRAGE), which correlated significantly with sRAGE (r=0.88, P<0.001).
We conclude that in HD patients, sRAGE is increased due to decreased renal function, which is a very strong determinant of sRAGE levels, and is inversely related to inflammation. The highest sRAGE levels are influenced genetically. In our study, sRAGE levels were not related to mortality of HD patients.
晚期糖基化终末产物受体（RAGE）参与血管和炎症性疾病的发病机制。可溶性RAGE（sRAGE）可在生理上抑制经由RAGE介导的病理效应。我们的目的是研究血液透析（HD）患者的sRAGE和RAGE基因多态性。
共有261例病情稳定的HD患者纳入本研究，并进行了为期30个月的前瞻性随访。在研究开始时，测定sRAGE、炎症和营养参数。在214例HD患者的亚组中测定RAGE基因多态性。选取100名健康对照者作为比较组。
与健康对照者相比，HD患者的sRAGE水平升高（3427±1508 vs 1758±637 pg/ml，P<0.001）。它与残余尿量呈负相关（r=-0.193，P<0.05），与急性期反应物纤维蛋白原（r=-0.174，P<0.05）、血清类黏蛋白（r=-0.135，P<0.05）以及白细胞计数（r=-0.158，P<0.05）呈负相关。另一方面，它与糖尿病、心血管疾病、营养状况和死亡率无关。RAGE基因-429 CC和2184 GG多态性患者的sRAGE水平最高。内源性分泌型RAGE（esRAGE）的结果与sRAGE相同，且与sRAGE显著相关（r=0.88，P<0.001）。
我们得出结论，在HD患者中，sRAGE因肾功能下降而升高，肾功能是sRAGE水平的一个非常重要的决定因素，且与炎症呈负相关。sRAGE的最高水平受遗传影响。在我们的研究中，sRAGE水平与HD患者的死亡率无关。
