| Background and objectiveIdiopathic membranous nephropathy(IMN)has become one of the most common pathological types of primary nephrotic syndrome in adults.The prognosis of IMN varies widely among individuals,with about 50%patients who have persistent high-grade proteinuria developing to end-stage renal disease(ESRD)10 years later and a small percentage of patients with IMN experience spontaneous remission.Currently,it is believed that IMN is an autoimmune glomerular disease mediated by autoantibodies,and immunosuppressive therapy can effectively reduce proteinuria in IMN patients.However,immunosuppressants have a variety of adverse effects,and the application time and type selection are of great significance to the long-term prognosis of patients.The classical immunosuppressive therapy is glucocorticoid combined with oral cyclophosphamide.However,as a cytotoxic drug,cyclophosphamide can produce some serious adverse effects,such as severe myelosuppression,gonadal function damage,pulmonary infection and hemorrhagic cystitis,which limit its clinical application.In 2012,The Kidney Disease:Improving Global Outcomes(KDIGO)recommended that calcineurin inhibitors(CNIs)can be an alternative initial therapy of IMN.Tacrolimus is the representative of CNIs,and a large number of randomized controlled studies have confirmed the efficacy of tacrolimus combined with glucocorticoid in treating IMN.However,long-term use of glucocorticoids increased the risk of infection,femoral head necrosis,osteoporosis,central obesity and steroid diabetes mellitus.In 2007,Praga et al demonstrated for the first time that tacrolimus monotherapy was effective for the treatment of IMN,but the trail used non-immunosuppressive therapy as control.In 2017,Liang et al compared tacrolimus alone with intravenous cyclophosphamide combined with oral glucocorticoid,the two groups had similar remission rates after 12 months.Since then,there have been few studies compared tacrolimus monotherapy with the classical regimen.To further verify the efficacy and safety of tacrolimus alone in the treatment of IMN,a retrospective study was conducted to compare the efficacy and safety of tacrolimus monotherapy with oral cyclophosphamide combined with glucocorticoid in treating adults-IMN.MethodsThis study adopted the method of retrospective cohort study.51 patients with renal-biopsy proven IMN hospitalized in the Department of Nephrology in First Affiliated Hospital of Zhengzhou University from June 2016 to December 2018 were enrolled in the study.According to the different initial treatment regimen,they were divided into tacrolimus(TAC)group and cyclophosphamide combined with glucocorticoid(CTX+GC)group.TAC group(n=34)received tacrolimus alone at an initial dose of 0.05 mg/kg/d,which was divided into two equal doses at a 12-hour interval and the dose was adjusted according to the blood concentration of tacrolimus.The induced remission stage was at least 6 months.The blood concentration of tacrolimus was maintained at 5～10.ng/ml in the induced remission stage.After achieving complete remission,tacrolimus was reduced regularly and gradually discontinued.CTX+GC group(n=17)received cyclophosphamide orally with a dose of 100mg/d,which was divided into two equal doses,until achieving the accumulated dosage of 150mg/kg.Prednisone were taken orally at an initial dose of 0.5 mg/kg/d at the same.time.After 8 weeks,the dose was reduced by 5mg every 4-8 weeks to 10mg/d for maintenance.The treatment period of both groups was at least 12 months.We collected at least 12-month clinical data,including the level of 24-hour proteinuria,serum albumin,serum creatinine and tacrolimus concentrations,to assess treatment effectiveness.Meanwhile,elevated blood glucose,infection,gastrointestinal symptoms,abnormal liver and renal function and other adverse effects were recorded.ResultsThe median follow-up time of our study was 20(12,35)months.At the 3rd,6th and 12th month of follow-up,the complete remission rates in the TAC group were 5.9%,23.5%and 38.2%,respectively,and the total remission rates were 47.1%,64.7%and 79.4%,respectively.The complete remission rates in the CTX+GC group were 5.9%,23.5% and 35.3%,respectively,and the total remission rates were 35.3%,70.6%and 82.4%,respectively.There was no statistically difference in remission rates between the two groups at each point of follow-up(P>0.05).After 12 months of treatment,the level of 24-hour proteinuria in both groups were significantly decreased[TAC group:(6.6 ±2.8)g before treatment,(1.2 ± 1.6)g after treatment;CTX+GC group:(7.7±3.3)g before treatment,(2.1±2.5)g after treatment],serum albumin were significantly increased[TAC group:(25.0±4.4)g/L before treatment,(38.4 ± 5.2)g/L after treatment;CTX+GC group:(23.5±4.4)g/L before treatment,(36.3 ± 4.2)g/L after treatment],the differences before and after treatment were statistically significant(P<0.01).The serum creatinine levels in both groups were stable[TAC group:(68.8±19.5)μmol/L before treatment,(74.4±19.1)μmol/L after treatment;CTX+GC group:(72.8 ± 16.3)μmol/L before treatment,(74.6 ±14.5)μmol/L after treatment],there was no statistically significant difference between before and after treatment(P>0.05).The main side effects in the TAC group included limb tremor,renal impairment and infection.And some of the side effects were alleviated after the tapering of tacrolimus.The main side effects in the CTX+GC group included leukopenia,abnormal transaminase,infection and gastrointestinal symptoms.The total incidence of adverse effects in the CTX+GC group was higher than that in the TAC group,the difference was statistically significant(P=0.028).ConclusionTacrolimus monotherapy can effectively reduce proteinuria and improve serum albumin level of IMN patient,the remission rate is comparable to the regime of oral cyclophosphamide combined with glucocorticoid.And tacrolimus monotherapy has a lower incidence of adverse effects and may be safer than the regime of oral cyclophosphamide combined with glucocorticoid. |
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