The Clinical Observation Of Tacrolimus Or Cyclosporine Combined With Corticosteroids In Treating Patients With Idiopathic Membranous Nephropathy

Background and aim Idiopathic membranous nephropathy(IMN)is one of the most common pathological types of nephrotic syndrome in adults accounting for 20% to 40% of primary nephrotic syndrome in adult patients.The fundamental pathological mechanism of IMN is that immune complex deposits under glomerular basement membrane(GBM)and the GBM diffusely thicken with spikes.Its pathogenesis is still unclear,most scholars think that abnormal activation of the immune system is essential for the occurrence and development of IMN at present,but IMN is also regarded as a podocytopathy and podocytes play an important role in the process of proteinuria and renal function loss.The clinical natural course of IMN is variable and not easy to predict.Generally,about one third of patients achieve spontaneous remission,in another third,proteinuria persists for years,while the final third of patients are likely to develop end-stage renal disease(ESRD).Due to the large difference of prognosis,different susceptibility to therapy and great relapse rate after drug withdrawal,the treatment has been controversial.Reich H et.al recommended that immunosuppressive therapy should be given to the patients whose urinary protein excretion exceeds 3.5 g/d with renal function injury or proteinuria exceeds 8 g/d.The best proven therapy for patients with IMN is the combined of cyclophosphamide(CYC)and corticosteroids,which is also the preferred therapeutic regimen recommended by Kidney Disease Improving Global Outcomes(KDIGO).However,the potential side effects(such as gonadal dysfunction,lymphoma and bladder cancer)associated with the use of CYC and high recurrence rate after 12 months of treatment have left many physicians reluctant to use this regimen.So choosing an effective and low toxic immumosuppressant has always been a clinical problem to be solved.KDIGO guidelines recommend calcineurin inhibitors(CNIs,Cs A and TAC)as the replacement strategies of initial treatment for IMN patients.In precious studies,investigators performed trials to compare the effectiveness between different kinds of immunosuppresants in the treatment of IMN.However,there is a lack of randomized controlled study comparing the efficacy and safety between different kinds of CINs(TAC,Cs A)in treating adult patients with IMN.Therefore,we admitted 31 patients with IMN to compare the efficacy and safety between TAC and Cs A combined with corticosteroids in this randomized research.Methods 31 patients who were clinically diagnosed nephrotic syndrome and confirmed as IMN by renal biopsy in the first affiliated hospital of Zhengzhou university from Sep 2015 to Mar 2016 were recruited to our study.They were randomly administered TAC(n=16)or Cs A(n=15)combined with corticosteroids.Patients randomized to the TAC group were administered at 0.05-0.1 mg/kg/d and was divided into 2 equal doses at 12-hour intervals.The drug concentration was first checked after 1 week.We adjusted the dosage according to the whole blood concentration,with a target of 5-10 ng/m L.For the Cs A group,patients received Cs A at 3-5 mg/kg/d divided into two doses at intervals of 12 hours initially.The dose was adjusted to achieve a blood trough concentration of 100-200 ng/m L.Lower blood trough concentration levels of TAC or Cs A were accepted if patients were in remission.Both groups received oral prednisone at a dose of 0.5 mg/kg/d.Then we further tapered the dosage slowly down to a dosage of 10 mg/d and maintained that dosage throughout the remainder of the 6-month therapy period.Laboratory evaluation including serum levels of creatinine,alanine aminotransferase,24-hour urinary protein,albumin,total cholesterol,triglycerides,glucose,as well as complete blood counts was measured at baseline and at monthly intervals for 6 months.Physical examination and screening for side effects were also performed at each visit.The patients were followed for 6 months.Results After 6 months of therapy,the percentages of remission(either CR or PR)in the TAC group vs.Cs A group were 87.5% vs.73.3%(P =0.318),respectively.While,the percentages of complete remission(CR)in the TAC group vs.Cs A group were43.8% vs.33.3%(P =0.552).In addition,mean time to PR was 2.4±1.3months in the TAC group vs.3.5±1.6 months in the Cs A group(P=0.045).Hyperuricemia,hyperglycemia and hand tremor tended to be more common in the TAC group than in the Cs A group.However,common adverse effects in the Cs A group included hypertrichosis and gingival hyperplasia.All of those side effects were under control after drug withdrawal.Conclusion TAC or Cs A combined with corticosteroids was both useful for adults with IMN.But TAC was not inferior than Cs A in efficacy.Otherwise,TAC and Cs A had different side effects,so CNIs should be used individualizedly in patients with IMN.