Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Nephrology (Carlton). 2012 May;17(4):338-45. doi: 10.1111/j.1440-1797.2012.01575.x.
Endothelial dysfunction occurs in nephrotic syndrome (NS) and may constitute a link between NS and vascular complications. Focal segmental glomerulosclerosis (FSGS) is a common cause of NS. This study aimed to assess endothelial markers at different stages of FSGS and define whether they were associated with thromboembolic complications and disease activity.
Forty-four patients with nephrotic-range proteinuria and biopsy-proven primary FSGS were included in this study. Nine of them had concurrent thromboembolisms. Thirty-two sex- and age- matched healthy volunteers served as controls. Endothelial markers including circulating endothelial cells (CECs), soluble thrombomodulin (sTM), von Willebrand factor (vWf), soluble vascular cell adhesion molecule-1 (sVCAM-1) and sE-selectin were assessed at the commencement of the study in all participants and were repeated at 2, 6 and 12 months of follow-up in patients without thromboembolisms.
Patients with FSGS during active stage showed significantly higher levels of CECs, sTM, vWf, sVCAM-1 and sE-selectin when compared with controls. Moreover, patients with thromboembolisms had higher CECs and vWf than those without thromboembolisms. In patients without thromboembolisms, endothelial markers except sE-selectin had inverse correlations with serum albumin and were positively related to cholesterol. Multiple analyses showed that cholesterol and serum albumin were independent predictors of CECs and sTM, and vWf and sVCAM-1, respectively. At follow-up, these markers systematically decreased as the disease went into remission, but the increase in vWf and sVCAM-1 persisted even in patients obtaining complete remission for nearly a year. In patients with no response, levels of endothelial markers exhibited no obvious change.
Patients with FSGS had elevated markers of endothelial dysfunction, which were largely related to the activity of the disease. Meanwhile, levels of CECs and vWf were higher in patients concurrent with thromboembolisms.
肾病综合征(NS)患者存在血管内皮功能障碍,这可能是 NS 与血管并发症之间的联系。局灶节段性肾小球硬化(FSGS)是 NS 的常见病因。本研究旨在评估 FSGS 不同阶段的内皮标志物,并确定其是否与血栓栓塞并发症和疾病活动相关。
本研究纳入了 44 例肾病范围蛋白尿且经活检证实为原发性 FSGS 的患者。其中 9 例并发血栓栓塞。32 名性别和年龄匹配的健康志愿者作为对照组。所有参与者在研究开始时评估内皮标志物,包括循环内皮细胞(CEC)、可溶性血栓调节蛋白(sTM)、血管性血友病因子(vWf)、可溶性血管细胞黏附分子-1(sVCAM-1)和可溶性 E-选择素,并在无血栓栓塞的患者中分别于 2、6 和 12 个月时进行重复检测。
活动期 FSGS 患者的 CECs、sTM、vWf、sVCAM-1 和 sE-selectin 水平明显高于对照组。此外,并发血栓栓塞的患者的 CECs 和 vWf 水平高于无血栓栓塞的患者。在无血栓栓塞的患者中,除 sE-selectin 外,内皮标志物与血清白蛋白呈负相关,与胆固醇呈正相关。多元分析显示,胆固醇和血清白蛋白是 CECs 和 sTM 以及 vWf 和 sVCAM-1 的独立预测因子。在随访中,随着疾病缓解,这些标志物系统地下降,但即使在近一年完全缓解的患者中,vWf 和 sVCAM-1 的增加仍持续存在。在无反应的患者中,内皮标志物水平无明显变化。
FSGS 患者存在血管内皮功能障碍的标志物升高,这在很大程度上与疾病的活动度有关。同时,并发血栓栓塞的患者的 CECs 和 vWf 水平更高。