Efficacy Of Multitarget Therapy With Refractory Idiopathic Membranous Nephropathy

ObjectiveIdiopathic membranous nephropathy(IMN)is a common pathologic type of nephrotic syndrome(NS)in adults,and part of the patients were resistant to a wide variety of immunosuppressives.The aim of the study is to observe the efficacy and side-effects of multitarget therapy in treating patients with refractory IMN.Methods45 patients with refractory idiopathic membranous nephropathy were recruited in this randomized controlled trial,23 receiving multitarget therapy,including tacrolimus(Tac),mycophenolate mofetil(MMF)and low-dose steroids,while 22 receiving cyclophosphamide(CYC)and prednisone.The initial dose of Tac was 0.05 mg/kg/d combined with 1.0 g/d MMF,and the 24-hour trough blood concentration(C0)of Tac was approximately 3-6 ng/ml.The CYC group received daily oral CYC 100mg/d for 3 months(accumulated dosage was 9g).Both groups received oral prednisone 0.5mg/Kg/d for 8 weeks and tapered gradually.The primary outcome was the number of partial or complete remessions in proteinuria at months 3 and 6.The secondary outcome was the cumulative percentage of patients whose creatinine increased >30% of the basal value.ResultsOf the 40 patients who completed the 6-month treatment,complete remission(CR)occurred in 3(15%)of the CYC group and 6(30%)of the multitarget therapy group;partial remission(PR)occurred in 5(25%)of the CYC group and 9(45.0%)of the multitarget group.The probability of overall remission(CR and PR)was significantly higher in the multitarget group than in the CYC group(p = 0.013,by log-rank test).Furthermore,a significantly greater improvement in proteinuria was observed in the multitarget group compared with the CYC group.No obvious nephrotoxicity and other serious side-effects were found in the multitarget group.ConclusionsIn this trial,low-dose steroids combined with Tac and MMF were effective and safe in refractory IMN.The treatment of refractory cases with multitarget therapy is promising.