Clinical significance of adanced glycation end products and inflammation products in the development of vascular calcification and cardiovascular complications in chronic kidney disease

F. U. Dzgoeva, O. V. Remizov, Z. R. Ikoeva, V. G. Goloeva, A. A. Gusalov
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Abstract

Background . Vascular calcification underlies cardiovascular complications, which remain the leading cause of high mortality in chronic kidney disease (CKD). Uremic toxins, including the advanced glycation end products, play a significant role in the formation of this process. The Aim of the study is to clarify the role of the advanced glycation end products (AGEs) and inflammationproducts in the processes of vascular calcification at different stages of CKD. Patients and Methods. 105 patients aged 18 to 66 years at different stages of CKD C1-C5D were examined, 75 of which were caused by diabetic nephropathy (DN), 30 by other nosological forms. Serum concentrations of AGEs, IL6, TNF-α, troponin I, parathyroid hormone (PTH) were determined by enzyme immunoassay (ELISA). To study the AGEs concentration, the serum was separated by centrifugation (in Eppendorf tubes). The samples were stored at – 70 °C. The left ventricular myocardial mass index (LVMI) was determined. Left ventricular hypertrophy (LVH) was diagnosed with LVH>115 g/m 2 for men and >95 g/m 2 for women. The peak systolic velocity of blood flow in the aortic arch (Vps) was studied by duplex scanning using the Doppler effect. Results . A significant increase in serum phosphorus concentration (p < 0.05) and PTH (p< 0.01) was revealed as the glomerular filtration rate decreased. An increase in the concentration of AGEs, IL6 and TNF-α was found at all stages of CKD, most pronounced at the later stages – C4-C5D ((p< 0.01, p< 0.05, p<0.05, respectively). Pronounced changes in LVMI and Vps were associated with high levels of AGEs, IL6 and TNF-α. CONCLUSION. An increase in the level of glycation end products and inflammatory factors directly and reliably correlated with the severity of uremia and the severity of morphofunctional changes in the heart and aorta, which confirms their significant role in the development of cardiovascular complications in CKD. Keywords: advanced glycation end products, inflammation, vascular calcification, chronic kidney disease>˂0.05, respectively). Pronounced changes in LVMI and Vps were associated with high levels of AGEs, IL6 and TNF-α. Conclusion . An increase in the level of glycation end products and inflammatory factors directly and reliably correlated with the severity of uremia and the severity of morphofunctional changes in the heart and aorta, which confirms their significant role in the development of cardiovascular complications in CKD.
晚期糖基化终产物和炎症产物在慢性肾脏疾病血管钙化和心血管并发症发展中的临床意义
背景。血管钙化是心血管并发症的基础,是慢性肾脏疾病(CKD)高死亡率的主要原因。尿毒症毒素,包括晚期糖基化终产物,在这一过程的形成中起着重要作用。本研究的目的是阐明晚期糖基化终产物(AGEs)和炎症产物在CKD不同阶段血管钙化过程中的作用。患者与方法:对105例18 ~ 66岁不同分期的慢性肾病C1-C5D患者进行了检查,其中75例由糖尿病肾病(DN)引起,30例由其他病因引起。采用酶免疫分析法(ELISA)检测血清AGEs、il - 6、TNF-α、肌钙蛋白I、甲状旁腺激素(PTH)的浓度。采用离心分离法(epppendorf管)分离血清,测定血清中AGEs的浓度。样品保存在- 70°C。测定左室心肌质量指数(LVMI)。左心室肥厚(LVH)诊断为男性LVH>115 g/ m2,女性LVH> 95 g/ m2。利用多普勒效应,采用双工扫描技术研究了主动脉弓的血流峰值收缩速度。结果。血清磷浓度显著升高(p <0.05)和PTH (p<0.01),肾小球滤过率降低。AGEs、il - 6和TNF-α的浓度升高在CKD的所有阶段都发现,最明显的是在晚期- C4-C5D (p<0.01、术中;0.05, p<0.05)。LVMI和Vps的显著变化与高水平的AGEs、il - 6和TNF-α相关。结论。糖基化终产物和炎症因子水平的升高与尿毒症的严重程度以及心脏和主动脉形态功能改变的严重程度直接可靠相关,证实了它们在CKD心血管并发症发生中的重要作用。关键词:晚期糖基化终产物,炎症,血管钙化,慢性肾脏疾病(分别小于0.05)。LVMI和Vps的显著变化与高水平的AGEs、il - 6和TNF-α相关。结论。糖基化终产物和炎症因子水平的升高与尿毒症的严重程度以及心脏和主动脉形态功能改变的严重程度直接可靠相关,证实了它们在CKD心血管并发症发生中的重要作用。
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