血浆置换治疗清除抗肾小球基底膜抗体的效率及其与肾脏预后的关系

The efficiency of plasmapheresis on removing circulating antibodies against glomerular basement membrane and on renal survival

目的血浆置换治疗是清除循环中抗肾小球基底膜(glomerular basement membrane,GBM)抗体的重要手段,本研究分析了血浆置换治疗清除循环中抗体的效率、影响因素、及其与肾脏预后的关系。方法选取北京大学第一医院肾内科2009~2015年确诊抗GBM病且行血浆置换治疗的患者60例。血浆置换采用单重或双重置换,置换液采取5%白蛋白或新鲜冰冻血浆。计算血浆置换前后抗体下降的百分比,并收集患者的临床、病理及预后资料。结果 (1)血浆置换疗程结束后,有33/60例(55%)患者循环中的抗GBM抗体转阴,27/60例(45%)患者抗体未转阴、但抗体水平较治疗前显著下降。抗体未转阴的患者,治疗前的抗体水平更高(123.00比200.00 RU/ml,Z=-3.976,P<0.001)、联合激素冲击治疗的比例更低(30.80%比61.70%,χ~2=3.937,P=0.047)。抗体水平是决定血浆置换治疗后抗体能否转阴的独立危险因素(OR 7.727,95%CI 1.911~31.240,P=0.004)。(2)本研究的60例患者均存活,有38例(63.3%)进入终末期肾脏病(end-stage renal disease,ESRD)。这些患者诊断时的血肌酐(Z=-2.454,P<0.001)和抗GBM抗体的水平(Z=-2.089,P=0.037),少尿/无尿的比例(χ~2=6.334,P=0.012),均显著高于非ESRD患者,且血浆置换后抗体转阴的比例更低(χ~2=6.962,P=0.008)。2组患者接受血浆置换的次数(Z=-1.534,P=0.125)没有显著差异。诊断时的血肌酐水平(>600μmol/L)是患者最终ESRD的独立危险因素(OR13.824,95%CI 2.332~81.939,P=0.004)。结论血浆置换可以有效清除循环中的抗GBM抗体,抗体能否转阴主要取决于诊断时的抗体水平。血浆置换的次数与肾脏预后没有显著的相关性,诊断时血肌酐的水平是患者最终ESRD的独立危险因素。

Objective This study aimed to analyze the clinical features of anti-GBM patients with the treatment of plasmapheresis and to address the effect of plasmapheresis on removing circulating anti-GBM antibodies and on renal survival. Methods Sixty patients with anti-GBM disease in our department were enrolled, and all of whom received more than one session of plasmapheresis. The clinical features and the levels of anti-GBM antibodies before and after plasmapheresis were collected. Results （f）After plasmapheresis, circulating anti-GBM antibodies disappeared in 33/60 （55%） patients. Patients with negative circulating anti- GBM antibodies after plasmapheresis had a significantly lower level of initial anti-GBM antibodies on diag- nosis （123.00 vs. 200.00 RU/ml, Z=-3.976, P〈0.001） and a higher proportion of receiving intravenous pulse methylprednisolone （61.70% vs. 30.80%, ,x2=3.937, P=0.047）, compared to those who still had detectable cir- culating antibodies after plasmapheresis. The level of anti-GBM antibodies on diagnosis was the independent risk factor for antibody persistence after plasmapheresis （OR 7.727, 95% CI 1.911 ~31.240, P=0.004）. @In the present study, 38/60 （63.30%） patients progressed to end-stage renal disease （ESRD）. They presented higher levels of serum creatinine （Z=-2.454, P〈0.001） and anti-GBM antibodies on diagnosis （Z=-2.089, P= 0.037）, a higher proportion of oliguria/anuria （x2=6.334, P=0.012） and a lower proportion of antibody disap-pearance after plasmapheresis 0f=6.962, P=0.008）, compared to the patients without ESRD. There was no sig- nificant difference in the number of plasmapheresis sessions between patients with and without ESRD （Z=- 1.534, P=0.125）. Logistic regression model showed that renal survival was only predicted by serum creatinine （〉600~tmol/L） on diagnosis （OR 13.824, 95% CI 2.332~81.939, P=0.004）. Conclusions Circulating anti- GBM antibodies could be efficiently removed by plasmapheresis. The level of anti-GBM antibodies on diag- nosis was the independent risk factor for antibody persistence after plasmapheresis. Renal survival was pre- dicted by serum ereatinine （〉600μmol/L） on diagnosis, but had no significant correlation with the number of plasmapheresis sessions.