Clinical Observation Of Cyclophosphamide And Tacrolimus In The Treatment Of Idiopathic Membranous Nephropathy

Research purposes:Idiopathic membranous nephropathy(IMN)is one of the common pathological types of adult nephrotic syndrome,and is also a common cause of end-stage renal disease.The main clinical manifestation of idiopathic membranous nephropathy is persistent massive proteinuria,and its pathogenesis is still unclear.In recent years,it has been found that the antiphospholipase A2 receptor(PLA2R)antibody and the type 1 thrombospondin 7A domain(THSD7A)are serological markers of idiopathic membranous nephropathy(IMN)and are highly diagnostic in the clinical diagnosis of IMN.Specificity and sensitivity.This discovery not only reveals the immune mechanism of the disease,but also proves that IMN is an autoimmune disease and lays the foundation for the immunosuppressive treatment of the disease.At the same time,related research also found that PL2RAb titer le-vel can dynamically monitor disease activity and recurrence earlier,and better evaluate the prognosis of the disease.There is no uniform standard treatment plan for IMN clinical.Clinical practice has proven that IMN patients have poor efficacy with hormone therapy alone.At present,the treatment regimen uses hormone combined with cytotoxic drugs.The first-line clinical treatment options include cyclophosphamide(CTX),cyclosporine(CyA),and tacrolimus(TAC).The second-line regimen includes the mycophenolate mofetil(MMF)regimen and rituximab.Monoclonal antibody(RTX)protocol.CTX is a compound composed of nitrogen mustard and phosphoramide,and is a commonly used alkylation immunosuppressant in clinical practice.After the liver is metabolized by CTX,it forms a phosphoramide nitrogen mustard.CTX can interfere with DNA synthesis and has an immunological killing effect on cells with strong reproductive activity.The treatment of hormone combined with CTX is based on the combination of immunosuppressive therapy and cytotoxic drugs.The synergistic effect of the two drugs improves the remission rate of IMN and effectively reduces the urine protein content.Studies have confirmed that after treatment of IMN patients with CTX,the urinary protein is significantly reduced,the disease remission rate is higher,and renal function can be significantly improved.Especially for PLA2R-related IMN,the CTX program can effectively reduce the anti-PL2RAb titer level,and the therapeutic effect is remarkable.Tacrolimus(TAC)is a calcineurin inhibitor that interferes with calcium-dependent signaling pathways,blocks transcription of early T-cell lymphocytes,and inhibits T cell activation and proliferation.Furthermore,TAC exerts an immunosuppressive effect by inhibiting T cell-derived growth factors from inhibiting B cell growth and antibody formation.At the same time,TAC can be directly applied to the actin cytoskeleton of podocytes,which can reduce angiopoietin-like cells in podocytes,thereby reducing the production of urinary protein.TAC combined with low-dose steroids can significantly reduce urinary protein in patients with IMN in a short period of time,significantly shortening the time to induce clinical remission in patients with IMN compared with CTX.The use of the TAC regimen reduces the dose of hormones and reduces the side effects of hormones.Therefore,the application of this drug in the treatment of IMN has attracted more and more attention.Clinical studies have found that the TAC regimen induced a faster clinical remission of IMN compared to the CTX regimen 3 months ago,and the short-term efficacy of the TAC combined with low-dose steroid regimen was superior to the CTX regimen.After 6 months,the TAC regimen had no advantage over the CTX regimen,and the recurrence rate of IMN was higher after discontinuation of TAC.In the long run,the response rate and prognosis of the CTX regimen are superior to the TAC regimen.The CTX regimen often uses large doses of hormones,with relatively large side effects,and has adverse reactions such as myelosuppression and increased cancer risk.And related research found that the TAC program has a certain impact on the patient's renal function and blood sugar.Many studies have compared the efficacy and safety of the CTX regimen with the TAC regimen,but the results are inconsistent and the meta-analysis failed to give clear conclusions.The CTX and TAC programs are still controversial as the initial treatment for IMN.To this end,this paper aims to explore the effectiveness and safety of CTX and TAC in the treatment of IMN.Research method:Collection of 118 patients with membranous nephropathy diagnosed by renal biopsy from June 2011 to June 2016 in Shandong University.The basic information,clinical data and data were collected to exclude the failure to complete the impact treatment.Programmer or loss of follow-up(9 cases);use of cyclosporine or other immunotherapy regimen(4 cases);conservative treatment or hormone therapy alone(10 cases);secondary membranous nephropathy(5 cases);Severe complications(2 cases).A total of 90 patients with IMN were included in the clinical study.Sixty-three patients were treated with cyclophosphamide combined with a full-dose hormone(CTX group),and 27 patients were treated with TAC combined with low-dose hormone(TAC group).The patient's basic clinical data(gender,age,weight,occupation,etc.)were counted,and serological findings(serum albumin,24h urine protein,triglyceride,cholesterol,blood glucose,etc)were included in the inpatient and outpatient review of the patients included in the study.Biochemical ions and other related indicators),some patients tested anti-phospholipase A2 receptor antibodies.The clinical data collected from the two groups were statistically analyzed to compare the differences between the two treatment regimens before and after treatment.The effectiveness,safety,and adverse effects of the two regimens were counted.The measurement data of the two treatment plans were analyzed by t test,and the count data were analyzed by chi-square test.Research result:After treatment with CTX or TAC,the urinary albumin was significantly decreased and serum albumin was significantly increased in both groups.There was significant difference before and after treatment(P<0.05).In the third month,the improvement of 24h urine protein and serum albumin in CTX group was not better than that in TAC group(P<0.05).The remission rate in CTX group was lower than that in TAC group(33.33%vs 66.67%,P=0.002),completely The remission rate was lower than that of the TAC group(9.52%vs 37.04%,P=0.003)At the 12th month,the improvement of 24h urine protein and serum albumin in CTX group was better than that in TAC group(P<0.05).The remission rate in CTX group was higher than that in TAC group(88.88%vs 70.37%%,P=0.031),complete remission.Rate(58.25%vs 40.74%P=0.015)The reduction of creatinine in CTX group was better than that in TAC group at 12 months(P=0.001)At 12 months,creatinine in CTX group was lower than that in TAC group(P=0.001).During the follow-up experiment,13 adverse reactions occurred in CTX regimen and 5 in TAC regimen.There were no serious adverse reactions in both regimens.Analysis conclusion:Both regimens were significantly better after treatment of IMN than before treatment.At the 3rd month,the CTX regimen was not superior to the TAC regimen,and the 12th month was superior to the TAC regimen.With the accumulation of CTX dose,the complete remission rate of CTX regimen gradually increased,and no serious adverse reactions occurred in either regimen.