局灶节段性肾小球硬化患者内皮细胞功能异常及临床意义

Endothelial dysfunction in patients with focal segmental glomerulosclerosis

目的:前瞻性观察局灶节段性肾小球硬化(FSGS)患者的内皮细胞功能及其与疾病活动程度和并发症的关系。方法:63例经肾活检及临床确诊且蛋白尿≥3.5g/d的特发性FSGS患者进入本研究,选取年龄、性别相匹配的32例健康志愿者作对照。分析内皮细胞损伤指标循环内皮细胞计数(CECs)、血管性血友病因子(vWF)、可溶性血栓调节蛋白(sTM)、血管细胞粘附分子(VCAM)和E选择素(ES)的阳性率,观察起点内皮细胞损伤指标与其他临床指标及静脉血栓栓塞(VTE)并发症的关系,观察内皮细胞损伤指标的动态变化。结果:(1)FSGS患者的各项内皮细胞损伤指标均显著高于正常对照组。(2)无VTE的52例患者内皮细胞损伤指标的阳性率分别为CECs48.1%、vWF92.3%,sTM96.2%,VCAM67.3%,ES28.9%,其中VCAM阳性患者的血压水平、尿蛋白定量、血肌酐水平及肾小管损伤指标NAG酶、RBP均显著高于阴性者,CECs及ES阳性与阴性患者各项指标间无明显差异。相关性分析显示,sTM、VCAM与SCr显著正相关,VCAM、vWF与NAG、RBP均有正相关性。随访2月时15例达完全缓解(CR),13例部分缓解(PR),15例无效(NR),8例失随访,1例进入腹膜透析治疗退出本研究。CR组治疗后sTM、VCAM均明显下降,而vWF、ES水平变化不明显,PR组治疗前后相比sTM明显下降,余三项指标变化无统计学意义,NR组治疗前后各项内皮损伤指标均无明显变化。随访1年期间11例患者获得持续缓解,该组患者各观察点ES水平与正常对照组均无明显差异,sTM于随访2月时即降至正常,VCAM、vWF分别于随访2月、6月时开始下降,随访12月时仍高于正常对照。(3)合并VTE者CECs、vWF水平显著高于无VTE者。结论:FSGS患者存在明显内皮细胞功能异常,其中VCAM及CECs水平的异常升高分别与疾病的活动程度及血栓栓塞并发症的发生关系密切,随疾病的缓解内皮细胞功能得以不同程度的改善。内皮细胞损伤标志物的检测有助于对FSGS患者的病情及血栓栓塞并发症进行评估。

Objective：To find out the association between endothelial dysfunction and the disease activity markers of endothelial dysfunction in patients with focal segmental glomerulosclerosis（FSGS） at different stages of the disease were assessed. Methodology：Sixty-three patients with FSGS （aged 10 to 59 years） and 32 sex- and agematched healthy volunteers were included in this longitudinal study. Among these patients, 11 cases complicated with venous thromboembolism （VTE）. Markers of endothelial dysfunction including circulating endothelial cells （CECs）, yon Willebrand factor （vWF）, soluble thrombomodulin （sTM）, vascular cell adhesion molecule （VCAM） and E-selectin （ES） were assessed at baseline. Markers except CECs were rechecked after 2, 6, and 12 months＇treatment. Results：Patients with FSGS had significantly higher plasma levels of CECs, vWF, sTM, VCAM and ES compared to controls. In patients without VTE, the positive rates of CECs, vWF, sTM, VCAM and ES were 48. 1%, 92. 3%, 96. 2%, 67.3% and 28.9%, respectively. Both sTM and VCAM were positively related to serum creatinine. VCAM as well as vWF was also correlated significantlywith urine NAG and RBP. After 2 months therapy, 8 cases were lost to follow up, 15 achieved complete remission （CR）, 13 got partial remission（PR）and 15 had no response （NR）, 1 was withdrawn as she went into peritoneal dialysis. The plasma levels of all the markers studied befbre and after treatment were not significantly different in NR group, but in PR group, the level of sTM decreased significantly, while the other three markers had no obvious change. Patients who achieved CR had significantly decreased plasma levels of sTM and VCAM, but the levels of vWF and ES did not change significantly. There were 11 patients who obtained continuous complete remission （CCR） during the one year follow up. Markers of endothelial dysfunction in these patients decreased systematically to normal levels except vWF and VCAM, the levels of which remained higher than those of controls. The levels of CECs and vWF were higher in patients with VTE than those without VTE. Conclusion：Patients with FSGS had endothelial dysfunction which is related to the disease activity and VTE complications. Modulation of endothelial function may offer a novel strategy to reduce renal insult and complications.