Analysis Of The Efficacy And Safety Of Tacrolimus In The Treatment Of Lupus Nephritis

Background:Systemic lupus erythematosus(SLE)is a prototypical autoimmune disease characterised by alternating periods of disease activity and quiescence.The altered T cell function and activation of polyclonal B cells,followed by the production of autoantibodies such as anti-dsDNA,results in the deposition of immune complexes in multiple organs,particularly in the kidney.These deposits drive local inflammatory reactions,leading to tissue damage and clinical disease.Lupus nephritis(LN)is an immune complex glomerulonephritis that develops as one of the most serious complication of systemic lupus erythematosus,and the mortality rate is high.Asymptomatic proteinuria,nephritic syndrome,nephrotic syndrome and rapidly progressive glomerulonephritis are some important clinical manifestations of LN.In America and Europe,the ten year renal survival rate has improved to 80–90%with the implementation of current immunosuppressive regimens.The main aim of treatment is to control inflammatory disease activity and prevent flares of disease while in remission.~1 The mortality and morbidity associated with SLE have improved significantly over the past 50 years owing to introduction of treatments such as corticosteroids,antimalarial agents(AMs),immunosuppressive(ISS)drugs and more recently,biological agents.Although such treatments have improved disease control,all are associated with potential long-term sequelae that can adversely affect patient outcomes and may produce some of the more obvious short-term side effects,thus limiting the clinical application of some drugs.At present,the gold standard for the treatment of this disease is still the combined treatment of glucocorticoid and immunosuppressive cyclophosphamide.Before clinical application,it is necessary to weigh the advantages and disadvantages and obtain the consent of my own and family members before use,due to bone marrow suppression,infection,abnormal liver function,Various adverse outcomes such as bladder toxicity,hair loss,and gonadal suppression may sometimes be discarded,So sometimes it will give up the application of the drug.Therefore,we need to continuously explore new immunosuppressive drugs such as tacrolimus to treat LN,so as to control the disease satisfactorily,achieve clinical remission,reduce adverse reactions,improve patient prognosis and improve quality of life.Objective:A retrospective study was performed using cyclophosphamide(CTX)plus glucocorticoid(GC)as a control to observe the novel immunosuppressant tacrolimus(FK506)combined with glucocorticoid(GC)in the treatment of lupus nephritis(LN)clinical efficacy and safety,to provide reference basis for clinical diagnosis and treatment.Method:A retrospective analysis of 42 patients with lupus nephritis hospitalized from January 2016 to January 2017 to the First Affiliated Hospital of Zhengzhou University.The diagnosis of the disease was in line with the lupus developed by the International Society of Nephrology and the Institute of Renal Pathology(ISN/RPS)in 2003.After renal biopsy,the pathological types were identified as type III,type IV,type V,type III+V and type IV+V.The 42 patients enrolled were divided into 2groups,21 in each group.The two groups were treated with tacrolimus and cyclophosphamide,respectively,and were combined with glucocorticoid drugs.The CTX drug regimen was used for every 0.5g/m~2 body surface area,1 times a month,and 6 months after continuous-use to every 3 months;FK506 was administered by0.1mg/(kg·d),which was taken orally for 12 hours at two intervals;During the drug administration,the serum concentration was monitored and the therapeutic dose was adjusted according to the index;The medication principle of GC in the two groups is the same,for patients with severe lupus,startting with 0.5-1.0g/d shock treatment for3 days,oral dose of 1.0mg/(kg·d)a morning meal,after 4~8 weeks,every 2 weeks minus by 5.0mg/d to 20.0mg/d,then every 2 weeks minus by 2.5mg/d to 10.0mg/d,then maintenance treatment,and follow-up time was 1 years.Record and compare the two groups before and after treatment in patients with 24h urine protein quantitative,serum albumin,serum creatinine,urea nitrogen,ESR,C3,positive rate of anti ds-DNA antibody and SLEDAI score indexes,and analysis the treatment effect of two groups of patients and the time showing effect,and at the same tine,compared two groups of patients with gastrointestinal symptoms,infection,abnormal liver function,transient elevated creatinine,bone marrow suppression,arrhythmia,abnormal glucose metabolism,menstrual disorders and other adverse reactions.SPSS17.0 statistical software was used to analyze the data.The measurement data were expressed as?x±s,and the t-test was used for comparison.The count data were expressed as the number of cases and percentage,and the?~2 test was used for comparison.The test level was 0.05.When P<0.05,the difference was considered statistically significant.Results:1.There was no significant difference in gender,age,course of disease and other general data between two groups;Before treatment,patients in two groups of baseline data such as 24h urinary protein quantitative,ALB,SCr,BUN,ESR,C3,positive rate of anti ds-DNA antibody and SLEDAI score also had no statistical significance(P>0.05).2.Two groups of patients after treatment in 24h urinary protein quantitative,SCr,BUN,ESR,positive rate of anti ds-DNA antibody and SLEDAI score were significantly lower than before treatment,while serum albumin and complement C3levels were significantly higher than before,the difference was statistically significant(P<0.05).3.After treatment of 1 years,24h urinary protein quantitative,SCr,BUN,positive rate of anti ds-DNA antibody,SLEDAI score of patients in the FK506 group reduced more significantly than that in CTX group,and the level of ALB and C3increased more significantly compared with CTX group,that the difference was significant(P<0.05);The difference in ESR between the two groups was insignificant(P>0.05).4.The patients in FK506 group were completely remitted of 14 cases,partially alleviated of 6 cases,and the effective rate was 95.24%;Twenty-one patients in the CTX group had complete remission in 6 cases after treatment,and another 8 had partial remission with an effective rate of 66.67%.The CTX group had a significantly lower treatment efficiency than the FK506 group,with significant differences(P<0.05).Meanwhile,the effect time of patients in FK506 group was obviously less than that of CTX group,and the difference was significant(P<0.05).5.In FK506 group,the total incidence rate of adverse reactions in patients with gastrointestinal symptoms,abnormal glucose metabolism and transient elevated creatinine was 19.05%;In CTX group,there were various types of adverse reactions,including gastrointestinal symptoms,infection,bone marrow suppression,arrhythmia,abnormal liver function,menstrual disorders,with the total incidence rate of 47.62%;The total incidence of adverse reactions in FK506 group was lower than that in the CTX group,and the difference was statistically significant(P<0.05).Conclusions:1.Both cyclophosphamide and tacrolimus can effectively control the condition and ameliorate multiple clinical laboratory parameters in patients with lupus nephritis.2.Tacrolimus combined with glucocorticoid treatment of lupus nephritis remission rate significantly higher than the traditional therapy,clinical onset of efficacy and efficacy.3.Tacrolimus has less side effects and better safety in the treatment of lupus nephritis.