A Prospective Controlled Clinical Study Of Different Therapeutic Regimens For Patients With Idiopathic Membranous Nephropathy

Objective:Immunosuppressive agents played an important role in the treatment of idiopathic membranous nephropathy. This study was designed to evaluate the efficacy and safety of Modified Ponticelli Regimen(MPR) compared with the usual regimen of China、 corticosteroid plus tacrolimus(TAC) as induction therapy for patients with idiopathic membranous nephropathy.Methods:42 nephrotic patients with biopsy-proven IMN were enrolled in this trial. They were randomly divided into three groups. In MPR group: patients were treated with 0.5g IV methylprednisolone daily(Days 1-3), then oral methylprednisolone(0.5 mg/kg/d) for 27 days(Days4-30) in the first 1, 3 and 5 month, 2, 4 and 6 months oral cyclophosphamide(2.0 mg/kg/d) for 30 days. In the usual regimen of China group: patients were treated with cyclophosphamide(oral 100mg/d,accumulation about 9g)combined with methylprednisolon(1.0mg/kg/d,tapered after 2-3 months). In TAC geoup: patients were treated with tacrolimus(oral 0.05-0.075mg/d,target trough blood concentration of 4-8 ng/m L) combined with corticosteroid(0.5mg/kg/d, tapered after 2-3 months).Results:At 3 months, in the MPR group 6 of 14 cases(42.9%) achieved PR and the total remission was 42.9%; in the usual regimen of China group 1 of 14 cases(7.1%) achieved CR, 5 cases(35.7%) achieved PR and the total remission was 42.9%; in the TAC group 7 of the 14 patients(50%) achieved PR and the total remission was 50%. Comparision of three groups, the TR rates of MPR group were not significantly different from the other two groups(P = 1.0, P = 0.71). At 6 months, in the MPR group 4 of 14 cases(28.6%) achieved CR, 5 cases(35.7%) achieved PR, and the total remission was 64.3%; in the usual regimen of China group 3 of 14 cases(21.4%) achieved CR, 6 cases(42.9%) achived PR and the total remission was 64.3%; in the TAC group 2 of the 14 patients(14.3%) achieved CR, 6 cases(42.9%) achieved PR and the total remission was 57.2%. Comparision of three groups, the TR rates of MPR group were not significantly different from the other two groups(P = 1.0, P = 0.71). The MPR group began to achieve remission at 3.3±1.5 months. The usual regimen of China group began to achieve remission at 3.5±1.9 months. The TAC group began to achieve remission at 2.5±1.2 months. The two groups separately compared with the MPR group, there was no statistically significant difference about the time of beginning to achieve remission(P > 0.05).At 3 months, urine protein decreased and serum album increased in three groups; total cholesterol decreased, but there was no statistically significant difference(P > 0.05); serum creatinine had no obvious changes(P > 0.05); in MPR group serum uric acid increased significantly(P < 0.05), but in the other two groups serum uric acid had no obvious changes(P > 0.05). At 6 months, urine protein decreased and serum album increased further in three groups; total cholesterol decreased significantly(P < 0.05); serum creatinine had no obvious changes(P > 0.05); in the TAC group the serum uric acid increased significantly(P < 0.05), but in the other two groups serum uric acid had no obvious changes(P > 0.05); in addition, in the usual regimen of China group triglycerides decreased obviously(P < 0.05). The other two groups compared with MPR group respectively, at 3 and 6 months, urine protein, serum albumin, total cholesterol, triglycerides and serum creatinine had no obvious difference(P > 0.05).During the treatment period, 16 patients showed moon face, namely, 5 in the MPR group, 6 in the usual regimen of China group, 5 in the TAC group. 3 patients had muscle pain of double lower limbs in 2, 4, 6 months when stopping using hormone,then spontaneous remission after 7-10 days. 2 patients in the usual regimen of China group had a temporary increase in transaminase. 2 patients in the usual regimen of China group and 2 patients in the TAC group suffered from respiratory system infections. 4 patients in the usual regimen of China group and 4 patients in the TAC group exhibited progressive diabetes.Conclusion:Three groups had the same clinical efficacy, including inducing remission, reducing urinary protein and total cholesterol, rising serum albumin etc. Serum creatinine had no obvious changes before and after treatment. Compared with the MPR group, the usual regimen of China group and TAC group were more likely to exhibite respiratory system infections and progressive diabetes. However, a longer followup was required to demonstrate the sustained efficacy and long-term side effect of MPR.