Clinical Efficacy And Safety Of Tacrolimus Versus Mycophenolate Mofetil In Children With Frequently Relapsing Or Steroid-dependent Nephrotic Syndrome

Background and ObjectivePrimary nephrotic syndrome(PNS)is a common chronic glomerular disease in children.Most of children respond well to steroids within 4 weeks(steroid-sensitive nephrotic syndrome,SSNS),while approximately half of which become frequently relapsing nephrotic syndrome(FRNS)or steroid-dependent nephrotic syndrome(SDNS).Children with FRNS/SDNS could be treated with immunosuppressive agents when low-dose alternative-day steroid therapy fails or when severe adverse effects of steroids develop.Immunosuppressive agents,such as tacrolimus(TAC)and mycophenolate mofetil(MMF),are commonly used in FRNS and SDNS.At present,there are few clinical studies comparing the efficacy of TAC and MMF and the conclusions are inconsistent.Our current study aimed to compare the clinical efficacy and safety of TAC and MMF in the treatment of FRNS/SDNS in children.MethodWe retrospectively analyzed 67 children with FRNS/SDNS treated with TAC or MMF in the First Affiliated Hospital of Zhengzhou University between June 2015 and November 2017.The patients were classified into two groups: 32 cases in TAC group received TAC 0.05~0.15 mg/(kg·d),and 35 cases in MMF group received MMF 20~30 mg/(kg·d).The follow-up period was at least 1 year,relapse rate,steroid dose and estimated glomerular filtration rate(eGFR)were compared between the two groups.Survival curves were estimated by the Kaplan–Meier method and cumulative relapse-free survival rate were compared using the log-rank test.Results1.The relapse rate decreased from 4.5(4.0,6.0)episodes per year before therapy to 0.5(0.0,1.0)episodes per year(P<0.001),and the steroid dose decreased from 1.12(0.71,1.50)mg/(kg·d)before therapy to 0.02(0.00,0.46)mg/(kg·d)(P<0.001)in TAC group at one-year follow-up;in the MMF group,the relapse rate decreased from 4.0(4.0,5.0)episodes per year before therapy to 1.0(0.0,2.0)episodes per year(P<0.001),and the steroid dose decreased from 0.95(0.63,1.43)mg/(kg·d)before therapy to 0.38(0.00,0.75)mg/(kg·d)(P<0.001)at one-year follow-up.2.At one-year follow-up,the relapse rate and steroid dose were significantly lower in TAC group than in MMF group(P=0.036,0.043),the cumulative relapse-free survival rate was significantly higher in TAC group than in MMF group(log-rank P=0.038);there was no significantly difference in eGFR between the two groups(P=0.767).3.There were 1 case of reversible posterior reversible encephalopathy syndrome and 1 case of severe pneumonia in TAC group,and no other serious adverse reactions were observed.There was no significant difference in the incidence of adverse reactions between the two groups.ConclusionBoth TAC and MMF were effective in the treatment of FRNS/SDNS in children,while TAC was superior to MMF in reducing the relapse rate,assisting steroid reduction,and maintaining remission.Most children could tolerate the treatment of TAC and MMF,but the drug toxicity of TAC should be closely monitored.