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成纤维细胞生长因子-23(FGF-23)/可溶性klotho蛋白(sKlotho)/骨硬化蛋白糖蛋白比值紊乱是接受常规血液透析或血液滤过治疗的终末期肾病(ESRD)患者发生心血管并发症的一个新的危险因素。

Fibroblast growth factor-23 (FGF-23) / soluble Klotho protein (sKlotho) / sclerostin glycoprotein ratio disturbance is a novel risk factor for cardiovascular complications in ESRD patients receiving treatment with regular hemodialysis or hemodiafiltration.

作者信息

Milovanova L Yu, Dobrosmyslov I A, Milovanov Yu S, Taranova M V, Kozlov V V, Milovanova S Yu, Kozevnikova E I

机构信息

I.M. Sechenov First Moscow State Medical University, Ministry of Health (Sechenov University), Moscow, Russia.

出版信息

Ter Arkh. 2018 Jun 20;90(6):48-54. doi: 10.26442/terarkh201890648-54.

Abstract

AIM

Aim of the study was to explore the role of the FGF-23/sKlotho/sclerostin ratio disturbance in the determining of cardiovascular risk in end stage renal disease (ESRD) patients, receiving treatment with regular hemodialysis (НD) or hemodiafiltration (НDF) online in Russia.

MATERIALS AND METHODS

42 patients with ESRD, at the age of 18-55 years, treated with HD or HDF on line for at least 6 months, were examined. 22 (52.3%) patients received traditional HD, the remaining 20 (47.7%) - HDF online. In all the patients, in addition to a general examination, the serum levels of FGF-23, sKlotho, sclerostine (by ELISA), their associations with cardiovascular risk factors (left ventricular hypertrophy (LVH), acute coronary syndrome (ACS), serum troponin I levels) with the numbers of techniques (ECG; Eho-CGF (with calculation of left ventricular myocardium mass index (LVMMI), as well as the relative thickness of the walls of the left ventricle (RWT); sphygmography (central (aortal) blood pressure (CBP), subendocardial blood flow (SBF) - by «Sphygmocor»), and the effect of regular HD and HDF on serum levels of the studied markers, were assessed.

RESULTS

An independent effect of FGF-23 on the risk of LVH, as well as on the increase of serum troponin I in the studied ESRD patients [β=3.576 p<0.01, and β=1.115, p<0.05, respectively] was found. Serum Klotho was the factor most associated with the CBP [β=-0.023; p<0.001]. The increased serum sclerostin was correlated with a lower incidence of both reduced SBF [r=0.492; p<0.05], symptoms of coronary heart disease [r=-0.449; p<0.05] and rhythm disturbances [r=-0.446; p<0.05]. In addition, in HD patients higher FGF-23 and lower Klotho and sclerostine serum levels were associated with: inadequate dialysis syndrome (Kt/V <1.1; r=0.463; p<0.05), chronic inflammation (C-reactive protein >10 mg/L; r=0.612; p<0.01), and with a decrease in serum albumin level (<35 g/l; r=0.459; p<0.05). The FGF-23/sKlotho/sclerostin ratio disturbance was more pronounced in patients treated with traditional HD then HDF online. A direct correlation (r=0.445; p<0.05) was established between FGF-23 serum levels and serum phosphorus, which was more pronounced in HD patients (r=0.545; p<0.01).

CONCLUSION

In HD and HDF ESRD patients, higher serum FGF-23 and lower sKlotho and sclerostin levels were associated with a chronic inflammation, malnutrition, secondary hyperparathyroidism, and may considered as predictors of cardiovascular complications such as LVH, ACS, rhythm disturbances, persisting of subincreased serum troponin I.

摘要

目的

本研究旨在探讨成纤维细胞生长因子-23(FGF-23)/可溶性klotho蛋白(sKlotho)/骨硬化蛋白比值紊乱在俄罗斯接受常规血液透析(HD)或在线血液透析滤过(HDF)治疗的终末期肾病(ESRD)患者心血管风险判定中的作用。

材料与方法

对42例年龄在18至55岁之间、接受HD或HDF在线治疗至少6个月的ESRD患者进行了检查。22例(52.3%)患者接受传统HD治疗,其余20例(47.7%)接受在线HDF治疗。对所有患者除进行常规检查外,还检测了血清FGF-23、sKlotho、骨硬化蛋白水平(采用酶联免疫吸附测定法),评估了它们与心血管危险因素(左心室肥厚(LVH)、急性冠状动脉综合征(ACS)、血清肌钙蛋白I水平)的相关性以及与技术指标(心电图;超声心动图-心脏超声检查(计算左心室心肌质量指数(LVMMI)以及左心室壁相对厚度(RWT));脉搏波描记法(中心(主动脉)血压(CBP)、心内膜下血流(SBF)-采用“Sphygmocor”))的相关性,以及常规HD和HDF对所研究标志物血清水平的影响。

结果

发现FGF-23对所研究的ESRD患者的LVH风险以及血清肌钙蛋白I升高具有独立影响[β=3.576,p<0.01,以及β=1.115,p<0.05]。血清Klotho是与CBP最相关的因素[β=-0.023;p<0.001]。血清骨硬化蛋白升高与较低的SBF降低发生率[r=0.492;p<0.05]、冠心病症状[r=-0.449;p<0.05]和心律失常[r=-0.446;p<0.05]相关。此外,在HD患者中,较高的FGF-23以及较低的Klotho和骨硬化蛋白血清水平与以下情况相关:透析不充分综合征(Kt/V<1.1;r=0.463;p<0.05)、慢性炎症(C反应蛋白>10mg/L;r=0.612;p<0.01)以及血清白蛋白水平降低(<35g/l;r=0.459;p<0.05)。FGF-23/sKlotho/骨硬化蛋白比值紊乱在接受传统HD治疗的患者中比在线HDF治疗的患者中更为明显。血清FGF-23水平与血清磷之间存在直接相关性(r=0.445;p<0.05),在HD患者中更为明显(r=0.545;p<0.01)。

结论

在HD和HDF治疗的ESRD患者中,较高的血清FGF-23以及较低的sKlotho和骨硬化蛋白水平与慢性炎症、营养不良、继发性甲状旁腺功能亢进相关,并且可被视为心血管并发症如LVH、ACS、心律失常、血清肌钙蛋白I持续升高的预测指标。

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