| Part Ⅰ The prognostic value of anti-PLA2 R antibody in primary membranous nephropathy Research purposesTo investigate the prognostic value of serum anti-PLA2 R antibodies in primary membranous nephropathy,and to analyze its ability to predict spontaneous remission or high-risk progression of disease,so as to better guide the choice of treatment options.Method1.The patients diagnosed as PMN by renal biopsy at Shanghai Changzheng Hospital from March 2014 to May 2016 were selected.Record the clinical data and pathological reports of the patients.Serum samples from these patients were collected on the day of renal biopsy.Serum samples were quantified using Euronell’s anti-PLA2 R antibody ELISA kit,and antibodies titer levels ≥20 RU/ml were positive.Observe the positive rate of anti-PLA2 R antibody in PMN patients,then divide antibody-positive PMN patients into low antibody group and high antibody group,so that all PMN patients are divided into anti-PLA2 R antibody-negative group,antibody low-level group and antibody High-level groups,then comparing the differences in clinical indicators of the three groups of patients.2.Through the electronic medical records system,telephone,WeChat and other methods,We followed up serum creatinine,24-hour urinary protein,serum albumin,and their treatment options,disease outcomes,and disease course characteristics in patients with PMN.Follow-up time is greater than 12 months.Then,the above data were compared between the three groups to analyze the predictive value of anti-PLA2 R antibody levels in the prognosis of PMN.Result1.A total of 96 patients with PMN were included in this study.60 of them were anti-PLA2 R antibodies positive,with a positive rate of 62.5%.According to serum anti-PLA2 R antibody titer levels were divided into three groups: antibody-negative group of 36 people(<20RU/ml),antibody low-level group of 30 people(20.2-83.3RU/ml)and antibody high-level group of 30 people(86.6-1048 RU/ml);The clinical baseline of the three groups of patients was analyzed by one-way ANOVA: The 24-hour urinary protein quantification had no statistical difference among the groups,P=0.067(P>0.05),but further comparisons between groups,the 24 h urinary protein level in the high antibodygroup was higher than the antibody negative group(P=0.033)(P<0.05).Also,there was a statistically significant difference between the total groups in serum albumin(P=0.009,P<0.05),the antibody-negative group> antibody low-level group> antibody high-level group in the serum albumin.2.The follow-up time of all patients was 30.8±5.9(14-44)months.Among them,27(28.1%)patients were conservative supportive treatment regimens,and the remaining 69 patients were treated with different regimens of immunosuppressive therapy.46(47.9%)patients with complete remission and 18(18.8%)patients with spontaneous remission,who were mainly distributed in the anti-PLA2 R antibody-negative group,and the chi-square test was statistically significant(P<0.01).16(16.7%)cases of disease progression were mainly distributed in the antibody high-level group,and the chi-square test was statistically significant(P<0.01).3.During follow-up,the time of complete remission or the time when the patient began to progress was recorded.Multivariate Cox regression analysis was performed.Analysis showed that the anti-PLA2 R antibody level was an independent factor affecting complete remission(P=0.001),and the trend of complete remission was PLA2 R antibody-negative Group> antibody low-level group> antibody high-level group,HR =4.815(95% CI: 2.065-11.226);In addition,analysis showed that 24-hour urinary protein and age were also independent factors that affected patients’ complete remission(P<0.05);On the other hand,the anti-PLA2 R antibody level was an independent factor affecting the patient’s disease progression(P=0.013).The trend of disease progression was anti-PLA2 R antibody high-level group> antibody low-level group> antibody-negative group,HR=0.146(95% CI: 0.032-0.668).ConclusionThe level of anti-PLA2 R antibody in patients with PMN was related to 24-hour urinary protein levels and serum albumin levels at the time of initial diagnosis;PLA2R antibody levels were independent factors affecting complete remission and progression of patients.The complete remission and spontaneous remission tendency of the antibody high-level group was lower than the antibody-negative group and the antibody low-level group.The progression of the disease is higher than the other two groups.Therefore,it is recommended that the antibody high-level group use immunosuppressive therapy early.Part Ⅱ Analysis of the efficacy of two immunosuppressive treatment regimens Research purposesAt present,the first-line immunosuppressive treatment options for PMN are hormone combined with cyclophosphamide(CTX)and hormone combined with calcineurin inhibitor(CNIs).In this study,we compared the effects of two immunosuppressive regimens: hormone combined with cyclophosphamide and hormone combined with cyclosporine.MethodRefer to the first part of the clinical data collected by patients with PMN,Through the electronic medical records system,telephone,WeChat and other methods,We followed up the patient’s treatment plan,disease outcome and disease course characteristics,then selected patients who received hormone combined with cyclophosphamide(CTX)or hormone combined with cyclosporine(CsA)for immunosuppressive therapy,and divided them into CTX group and CsA group.During the follow-up,we record the complications such as the time of complete remission or the time when the patient began to progress,and the complications such as relapse or serious adverse events during the treatment.The follow-up time was more than 12 months,and the clinical remission or progression of the two groups was compared.Then analyze the difference in efficacy between the two treatment options.Result1.A total of 69 PMN patients in the first part were immunosuppressed.Among them,28 patients were treated with hormone combined with CTX immunosuppression and 22 patients were treated with hormone combined with CsA immunosuppressive therapy.The24-hour urinary protein quantification in the two groups was 5.33±3.33(g/d)and5.81±3.72(g/d),and the eGFR was 96±24(ml/min/1.73m2)and 96±18(ml/min /1.73m2),The t-test was used to compare the results of the above two groups,and there were no statistical difference(P>0.05),The remaining gender,age,weight,serum creatinine,serum albumin,hemoglobin,total cholesterol,triglyceride and other indicators,there were also no statistical difference between the two groups(P> 0.05).2.In the CTX group,12(42.9%)patients had complete remission after treatment,and11(50%)patients in the CsA group had complete remission after treatment.The chi-square test showed no statistical difference(P>0.05).6(21.4%)patients in the CTX groupprogressed after the treatment and 2(9.1%)patients in the CsA group progressed after the treatment.The chi-square test showed no statistical difference(P>0.05).3.Comparing the complications of the two groups,the recurrence rate of CsA group(22.7%)was higher than that of CTX group(3.6%)(P=0.036),there was a statistical difference,and the incidence of adverse reactions was higher in CTX group(39.3%)The CsA group(13.6%)(P=0.045),there was statistically different.The adverse reactions in the CTX group were mainly impaired liver function,infection,and myelosuppression.The adverse reactions in the CsA group were mainly nephrotoxicity.4.During the follow-up,the time of complete remission or the time when the patient began to progress was recorded,and multivariate Cox regression analysis was performed.Analysis showed that the immunosuppressive treatment program was an independent factor that affected the complete remission time of patients(P<0.01)(P<0.05).The complete remission time of CsA group was earlier than that of CTX group,with HR=0.276(95% CI: 0.1-0.758).There was no statistical difference between the two groups in terms of disease progression time(P>0.05).In addition,multivariate Cox regression analysis showed that anti-PLA2 R antibody level was an independent factor in the progression of the disease(P=0.02)HR=0.053(95% CI: 0.004-0.626).ConclusionThere was no significant difference in the remission rate and progression rate of PMN regimen with hormone-combined CTX and hormone-combined CsA,but the complete remission time of CsA group was earlier than that of CTX group.In terms of complications,the recurrence rate in the CsA group was higher than that in the CTX group,and the incidence of severe adverse reactions was higher in the CTX group than in the CsA group. |
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