原发性膜性肾病患者血管性血友病因子裂解酶13的血浆水平及其临床意义

Plasma level and clinical significance of ADAMTS13 in patients with primary membrous nephropa⁃thy

目的原发性膜性肾病(primary membrous nephropathy,PMN)患者发生静脉血栓栓塞(venous thromboembolism,VTE)风险高,检测PMN并发VTE患者与未并发VTE患者的血管性血友病因子裂解酶13(ADAM metallopeptidase with thrombospondin type 1 motif 13A,DAMTS13)的血浆活性水平及探究其临床意义。方法纳入2019年9月至2021年9月在新疆维吾尔自治区人民医院住院治疗的30位PMN并发VTE患者做为MN血栓组、30例PMN未并发VTE的患者作为MN非血栓组、3位体检健康者作为健康对照组,用酶联免疫吸附试验测量入组者血管性血友病因子(von willebrand factor,vWF)及其特异性裂解酶ADAMTS13的血浆活性水平,并与临床资料作分析比较探究其临床意义。结果(1)PMN患者ADAMTS13的血浆水平较健康组低,差异具有统计学意义;(2)膜性肾病血栓组血浆ADAMTS13水平低于非血栓组,vWF及vWF/ADAMTS13比值高于非血栓组,差异均具有统计学意义(P<0.01);(3)PMN患者血浆ADAMTS13水平与血浆白蛋白(albumin,Alb)呈正相关(r=0.538,P<0.01),与24 h尿蛋白定量(r=-0.371,P<0.01)、总胆固醇(r=-0.363,P<0.01)和低密度脂蛋白(r=-0.407,P<0.01)、纤维蛋白原(r=-0.510,P<0.01)、白细胞介素-6(interleukin,IL-6)(r=-0.428,P<0.05)、D-二聚体(r=-0.404,P<0.05)呈负相关,但与血清M型磷脂酶A2抗原抗体水平无显著相关性(P>0.05);(4)ADAMTS13诊断PMN并发VTE的ROC曲线下面积为0.794(P<0.001),最佳临界值为65.95%(灵敏度为96.7%,特异度为53.3%),vWF/ADAMTS13比值诊断PMN并发VTE的ROC曲线下面积为0.831(P<0.001),最佳临界值为2.63(灵敏度为86.7%,特异度为66.7%)。结论PMN患者血浆ADAMTS13水平下降,并发VTE时下降更明显,其下降可能与患者肾功能、炎症因子、血脂水平、高凝状态相关,可能与PLA2R-Ab无相关性,且ADAMTS13可能对PMN并发VTE有预测价值,vWF/ADAMTS13比值预测作用可能更强。

Objective Patients with primary membrous nephropathy(PMN)have an elevated risk of venous thromboembolism(VTE).The aim of this study was to detect plasma level of ADAMTS13 in PMN patients complicated and uncomplicated by VTE and examine their clinical significance.Methods From September 2019 to September 2021,60 PMN patients were recruited and as⁃signed into two groups of complicated by VTE(PMN-VTE)and not complicated by VTE(PMN-notVTE)(n=30 each).And 30 healthy adults were selected as normal control group.Plasma level of von Willebrand factor(vWF)and its cleaving protease ADAMTS13 were measured by enzyme-linked immu⁃nosorbent assay(ELISA).Results ADAMTS13 level was significantly lower in PMN than normal con⁃trol group.Additionally,level of ADAMTS13 was significantly lower in PMN-VTE group than PMNnot-VTE group while level of vWF and ratio of vWF/AMADTS13 were significantly higher in PMNVTE group.Furthermore,ADAMTS13 level was correlated positively with plasma albumin(r=0.539,P<0.01)and negatively with vWF,24-hour urinary protein,cholesterol,low density lipoprotein,fi⁃brinogen,D-dimer,serum creatinine and interleukin-6.However,no association existed between levels of ADAMTS13 and PLA2R-Ab.And area of under ROC curve was 0.794(P<0.001)for ADAMTS13 diagnosing PMN with concurrent VTE and the optimal threshold value was 65.95%with a sensitivity of 96.7%and a specificity of 53.3%.And vWF/ADAMTS13 was 0.831(P<0.001)and the optimal threshold value was 2.63 with a sensitivity of 86.7%and a specificity of 66.7%.Conclusion ADAMTS13 level declines not only in PMN but also drops more in PMN complicated by VTE.Further⁃more a decline of ADAMTS13 level may be correlated with kidney function,inflammatory factor,blood lipid and hypercoagulable state.No significant difference was detected for PLA2R-Ab.And detecting plasma ADAMTS13 level is expected to predict PMN complicated by VTE while the ratio may be more predictive.