他克莫司联合激素治疗血清抗PLA_2R抗体持续高滴度的难治性特发性膜性肾病  

Tacrolimus combined with prednisone for treatment of refractory idiopathic membranous nephropathy with persistent high serum anti-phospholipase A_2 receptor antibody titers

作　　者：黄俊[1] 李剑文[1] 梁鸣[1] 秦曙光[1] 傅君舟[1] HUANG Jun;LI Jianwen;LIANG Ming;QIN Shuguang;FU Junzhou(Department of Nephrology , Guangzhou First People＇s Hospital, Guangzhou 510180, China)

机构地区：[1]广州市第一人民医院肾内科,广州510180

出　　处：《实用医学杂志》2018年第8期1355-1359,共5页The Journal of Practical Medicine

基　　金：广东省科技计划项目(粤科规划字[2011]177号第6项)

摘　　要：目的评估他克莫司联合激素对血清抗磷脂酶A2受体(PLA2R)抗体持续高滴度的难治性特发性膜性肾病患者的疗效和安全性。方法召集12例2012年6月至2016年6月间在广州市第一人民医院行常规免疫抑制剂(环磷酰胺、霉酚酸酯或环孢素A)联合激素治疗6个月以上无效且血清抗PLA_2R抗体持续高滴度的特发性膜性肾病患者进行一项开放前瞻性研究。这12例患者被分为两组:改用他克莫司联合激素方案随访治疗12个月的他克莫司组和继续原治疗方案或改用其它常规免疫抑制剂治疗方案继续随访治疗6个月的对照组。结果在入组治疗6个月末,他克莫司组患者尿蛋白定量和血清白蛋白等临床指标均较对照组明显改善(P<0.01),e GFR也比对照组高(P<0.05);而对照组依然存在大量蛋白尿和低蛋白血症,且e GFR也较入组前有显著下降(P<0.01)。治疗6个月后,对照组无一例患者血清抗PLA_2R抗体转阴,也无一例达到临床缓解;而他克莫司组有5例(83.3%)患者血清抗PLA_2R抗体转阴,并达到临床缓解,其中2例(33.3%)完全缓解,3例(50%)部分缓解;治疗12个月后他克莫司组更有4例(66.7%)患者完全缓解。结论血清抗PLA_2R抗体持续高滴度水平,可能是部分难治性特发性膜性肾病患者对常规免疫抑制剂治疗无效的原因。他克莫司联合激素方案可能是使此类患者抗体转阴并达到临床缓解的一种有效治疗方法。Objective To assess the efficacy and safety of tacrolimus combined with prednisone for treat-ment of refractory idiopathic membranous nephropathy（IMN）patients whose serum anti-phospholipase A_2 receptor（PLA2R）antibody titers were persistent high. Methods An open prospective study of 12 refractory IMN patientswas performed in Guangzhou First People′s Hospital between June of 2012 and June 2016. The 12 patients failed to re-spond after a standard course of 6 months in a conventional immunosuppressive therapy（cyclophosphamide,myco-phenolate mofetil or cyclosporine A）combined with prednisone and the patients′ serum anti-PLA_2R antibody titerswere persistent high. They were divided into two groups：The tacrolimus group received tacrolimus combined withprednisone for 12 months and the control group received the same or another conventional immunosuppressive therapyfor 6 months. Results At the end of the sixth month after enrollment,proteinuria and serum albumin levels in the ta-crolimus group were significantly improved as compared with those in the control group（P〈0.01）,and e GFR washigher in the tacrolimus group than in the control group（P〈0.05）. Severe proteinuria and hypoalbuminemia still re-mained in the control group,and e GFR in the control group declined significantly prior to enrollment（P〈0.01）. Af-ter 6-month treatment,none of the control group became negative for serum anti-PLA_2R antibody,and achieved clini-cal remission. Five patients（83.3%）in the tacrolimus group became negative for serum anti-PLA_2R antibody andachieved clinical remission（complete remission in two patients and partial remission in three）. After 12-month treat-ment,complete remission was achieved in four patients（66.7%）in the tacrolimus group. Conclusions Persistenthigh serum anti-PLA_2R antibody titers may be a cause of no response to a conventional immunosuppressive therapy inrefractory IMN patients. For these patients,tacrolimus combined with prednisone may be an effective alternative trea

关 键 词：他克莫司 抗磷脂酶A_2受体 膜性肾病 难治性 

分 类 号：R692[医药卫生—泌尿科学]