The Long-term Efficacy And Safety Study Of Tacrolimus Combined With Corticosteroids In The Treatment Of Idiopathic Membranous Nephropathy

Objective:To evaluate the long-term efficacy and safety of using the tacrolimus(TAC) combined with corticosteroids in treatment of idiopathic membranous nephropathy patients. To study the relationship between the plasma concentration of tacrolimus and the efficacy and the safety.Aimed to provide the better basis of evidence-based medicine for the clinical treatment of IMN patients.Methods: Eighty-one patients with biopsy-proved IMN and nephrotic syndrom were randomly divided into two groups from January 2011 to February 2013 in the General Hospital of Shenyang Military Region,the nephrology department.Among the81 patients,45 were male,36 were female.The age between 18 years old and 70 years old,the mean age was 43.13 years old.Randomly divided into two groups,TAC group(41):using tacrolimus plus corticosteroids to treat the IMN patients,tarcrolimus was given at 0.05-0.1mg/(kg·d) initially,once 12 hours,then monitoring the plasma concentration of tacrolimus.CTX group(40):using CTX plus corticosteroids to treat the IMN patients.The total cumulative dose CTX fluctuations in 0.15 to 0.2 g/kg.Once intravenous infusion at a dose of 0.6g,twice a month,and continuous use for 6months.Then,once 3 months.These two groups were given corticosteroids 0.75mg/(kg·d)initially,and regularly reducing the dose step by step.The patients were followed up for24 months.Result:After 24 months of treatment,the 24 hours urinary protein quantitation,ALB and TP of the patients in these two groups were improved significantly(p<0.01). After the treatment of 6 months and18 months,the total remission rate in TAC group were apparently higher than CTX group(p<0.05).After the treatment of 12 months and 24 months,the total remission rate between these two groups was approximate,with no statistical difference(p>0.05).After the treatment of 24 months,the complete remission rate in TAC group was apparently higher than CTX group(p<0.05).After the treatment of 18 months,the relapse rate in CTX group was apparently higher than TAC group(p<0.05).Treatment for 6 months and 12 months was positive correlation between the TAC blood drug concentration and treatment effect(p<0.05).Treatment for 18 months and 24 months was no correlation between the TAC blood drug concentration and treatment effect(p>0.05).The TAC treatment group completed treatment for 6 months, 12 months, 18 months and 24 months,the average blood concentrations were 5.65ng/ml, 4.86ng/ml, 2.83ng/ml and2.71ng/ml.The effective blood drug concentration range fluctuations in3.1~8.5 ng/ml,3.1~7.6ng/ml,1.4~4.56ng/ml, 1.4~4.35ng/ml.During the treatment,the incidence of abnormal glucose metabolism in TAC group was higher than the CTX group, statistically significant(p<0.05).Conclusion:After 24 months treatment,the complete remission in TAC group was apparently higher than CTX group.Using tacrolimus combined with corticosteroids to treat IMN was much better than CTX group in short-trem inducing remission and the complete remission in long-term treatment were better than CTX group.Using long-term and low blood concentration to treat IMN,the relapse in TAC group was lower than CTX group.In TAC group,the main adverse reactions was abnormal glucose tolerance.The incidence of abnormal glucose tolerance in the TAC group was higher than in the CTX group.In CTX group,the main adverse reactions was abnormal liver function.