他克莫司联合激素治疗特发性膜性肾病疗效及其抗PLA2R抗体对治疗的反应

目的：评价他克莫司（FK506）联合激素治疗特发性膜性肾病（IMN）的疗效，并分析血清抗M型磷脂酶A2受体（PLA2R）抗体对治疗的反应。方法：61例成人IMN患者，按照其选择不同免疫抑制剂的意愿分为FK506联合激素组（FK506组，n=24）和环磷酰胺联合激素组（CTX组，n=37），分析2组患者治疗第4、8、12和24周时的缓解率。应用ELISA法检测2组患者治疗前后血清抗PLA2R抗体，比较治疗前后抗体的变化及FK506组中抗体阳性与阴性患者治疗缓解率的差异。结果：治疗24周时FK506组和CTX组患者总缓解率分别为91.7%和64.9%，FK506组患者治疗缓解率明显高于CTX组（P<0.05）；FK506组患者治疗8、12和24周时总缓解率及治疗12和24周时部分缓解率高于CTX组（P<0.05）。治疗前FK506组和CTX组患者抗PLA2R抗体阳性率分别为75.0%和70.3%，治疗24周后2组患者抗PLA2R抗体的转阴率分别为61.1%和57.7%，但2组间比较差异均无统计学意义（P>0.05）。治疗24周后，FK506组中基线抗PLA2R抗体阳性和阴性患者的总缓解率分别为88.9%和100.0%，两者之间比较差异无统计学意义（P>0.05）。2组患者除激素特征性不良反应外，FK506组无高血糖、肾间质损害、肝损害和神经毒性等不良反应出现；CTX组出现轻度肝损害和胃肠道症状。结论：FK506联合激素治疗IMN的缓解率高于CTX联合激素治疗，且起效快、安全性较好。血清抗PLA2R抗体可随治疗后缓解转阴，但FK506和CTX组间抗体转阴率比较无明显差异，且FK506联合激素治疗IMN患者的缓解率与基线抗PLA2R抗体无关联。

Curative efficacy of tacrolimus combined with corticosteroids in treatment of idiopathic membranous nephropathy and response of anti-M-type phospholipase A2 receptor antibody to treatment

Objective:To evaluate the curative efficacy of tacrolimus (FK506)combined with corticosteroids in the treatment of idiopathic membranous nephropathy (IMN ), and to analyze the response of anti-M-type phospholipase A2 receptor (PLA2R)antibody to the treatment.Methods:Sixty-one adult IMN patients were divided into FK506 group (FK506 combined with corticosteroids,n = 24)and CTX group (cyclophosphomide combined with corticosteroids,n=37)according to their willing to the acceptance of different immunosuppressives. The remission rates of the patients at 4,8,12 and 24 weeks after treatment in two groups were analyzed.The ELISA method was used for the detection of serum anti-PLA2R antibodies of the patients before and after treatment.The antibody level changes were observed and the difference of remission rates was compared between the antibody positive patients and the negative patients in FK506 group.Results:The total remission rates of the patients in FK506 and CTX groups 24 weeks after treatment were 91.7% and 64.9% respectively and the total remission rate of the patients in FK506 group was significantly higher than that in CTX group (P < 0.05).The total remission rates at 8,12,24 week after treatment and the partial remission rates at 12 and 24 weeks in FK506 group were significantly higher than those in CTX group (P <0.05).The anti-PLA2R antibody positive rates in FK506 group and CTX group were 75.0% and 70.3%,respectively;the negative conversion rate of anti-PLA2R antibody at 24 weeks after treatment in two groups were 61.6% and 57.7%,respectively;there were no significant differences between two groups (P >0.05).The total remission rates of the antibody positive patients and negative patients at baseline in FK506 group 24 weeks after treatment were 88.9% and 100.0%,respectively;there was no significant difference (P > 0.05).Except the characteristic side effects of corticosteroids,the patients in FK506 group presented no hyperglycemia,tubulointerstitial damage,hepatic lesion or neurotoxicity. But the patients in CTX group showed mild hepatic lesion or gastrointestinal symptoms.Conclusion:The remission rate of FK506 combined with corticosteroids is higher than that of CTX combined with corticosteroids in the treatment of IMN patients.FK506 treatment has relatively rapid effect and less side effects as well.The negative conversion of serum anti-PLA2R antibody follows the remission after treatment;however,the negative conversion rate has no significant difference between FK506 group and CTX group.The remission rate of IMN patients treated with FK56 combined with hormone has no relationship with the baseline anti-PLA2R antibody.