Efficacy Of Glucocorticoid Combined With Mizoribine For The Treatment Of Idiopathic Membranous Nephropathy

Objective:(1)To compare the efficacy and adverse reactions of glucocorticoid combined with mizoribine with glucocorticoid combined with cyclophosphamide or tacrolimus in the treatment of idiopathic membranous nephropathy.(2)To study the clinical efficacy and safety of mizoribine,a new immunosuppressant,in treatment of idiopathic membranous nephropathy.Methods:(1)Subjects: 80 patients who were hospitalized in the Department of Nephrology of the First Hospital of Jilin University from January 2015 to March 2019 were selected.The inclusion criteria met:(1)Over 18 years of age;(2)Diagnosis was idiopathic membranous nephropathy and pathological classification was period???,and the severity of the disease required glucocorticoid and immunosuppressive agents for intervention;(3)no immunosuppressant contraindications;(4)Sign the informed consent form of immunosuppressant;(5)Regularly following up at the outpatient department of the Department of Nephrology of the First Hospital of Jilin University after discharge,and the follow-up informations were complete.(2)Methods: Patients were divided into mizoribine group(MZR group),cyclophosphamide group(CTX group),and tacrolimus group(TAC group),who duration of treatment were no less than 12 months.Enrolled patients were given mizoribine,cyclophosphamide,and tacrolimus combined with glucocorticoid therapy.The initial dose of prednisone was 0.8?1 mg/(kg·d),the maximum dose was not more than 60mg/d,and the dose taper off gradually after 8 weeks,and finally the minimum dose was maintained at 5 mg/d.Patients in the MZR group were given mizoribine at 150 mg/d.Patients in the CTX group were given cyclophosphamide 0.4?0.6 g intravenously at 2 weeks,or orally 50 mg twice a day,with a cumulative dose of 6?8 g discontinued.Patients in the TAC group were given 0.03?0.05 mg/(kg·d),taking the drug on every 12 hours,and the blood concentration of tacrolimus should be controlled at 5?8 ng/ml.General data such as age,sex,weight,laboratory and renal pathology grade of patients before treatment were collected retrospectively.Laboratory indicators such as 24-hour urinary protein,serum albumin,serum creatinine and so on at the 1,3,6,9 and 12 months of treatment were observed,and related adverse reactions were recorded.Using SPSS24 statistical software to analyze and compare the changes in clinical biochemical indicators.Results:(1)By March 2020,all 80 patients in this study had completed the 12-month follow-up observation.(28 cases in MZR group,27 cases in CTX group,and 25 cases in TAC group).(2)There were no significant statistical difference in general data and biochemical indicators before treatment between MZR group,TAC group and CTX group(P>0.05).Comparison in the three groups: urine protein level at each time point was significantly lower than that before treatment(P<0.05),and serum albumin level was significantly higher than that before treatment(P<0.05),indicating that the treatment was effective.The serum creatinine level in CTX group at each time point was significantly lower than that before treatment(P<0.05),and the eGFR level was significantly higher than that before treatment(P<0.05).Serum creatinine levels of the MZR group at 1,3 months than before the treatment had no significant change(P>0.05),but in 6,9 and 12 months than before the treatment decreased significantly(P<0.05).The eGFR level of MZR group at 1,3,6 months has no significant change than before the treatment(P>0.05),but at 9 and 12 months than before the treatment significantly increased(P<0.05).The serum creatinine and eGFR levels of TAC group at each time point were not statistically significant compared with those before treatment(P>0.05).Comparison between groups: the serum albumin levels of the three groups were statistically different at 3,6 and 9 months(P<0.05),further pairwise comparision suggesting that the serum albumin levels of the MZR group were higher than those of the CTX group(P<0.05).There were statistically significant differences in urine protein quantification,serum creatinine and eGFR at the 9th month between the three groups(P<0.05),further pairwise comparisons showed that the levels of urine protein and serum creatinine in the MZR group were lower than those in the CTX group,and the levels of eGFR were higher than those in the CTX group.However,there was no statistical significance in the comparison of the three groups at the 1st and 12 th month of treatment(P> 0.05).Comparison of efficacy: the earliest complete remission was found in the TAC group and the rate of complete remission at 3-9 months was higher than that in the other two groups,but the rate of complete remission at 12 months in the MZR group was higher than that in the TAC and CTX groups(43%vs32%vs11%).The total effective rate of MZR group at each time point was higher than that of TAC group and CTX group(At the 12 months of treatment:93%vs88%vs85%).Adverse reactions: compared with tacrolimus group and cyclophosphamide group,mizoribine group had a lower incidence of adverse reactions.Conclusions:At the 12 months of treatment,mizoribine combined with corticosteroids in the treatment of idiopathic membranous nephropathy can significantly reduce urinary protein level,improving hypoproteinemia and delaying the progression of renal insufficiency.At the 12 months of treatment,the total remission rate and complete remission rate of Mizoribine group was higher than that of tacrolimus group and cyclophosphamide group and the incidence of adverse reactions was not increased.