Study On The Effectiveness And Safety Of Cyclosporine A In The Treatment Of Primary Membranous Nephropathy

BackgroundIdiopathic membranous nephropathy(IMN) is an important glomerulonephropathy leading to nephrotic syndrome(NS). The incidence of IMN has had a rapid growth in recent years. Cyclosporine A(CSA) is an established option for treatment in IMN patients, which has achieved cumulative remission in up to 60%-90% of patients. The major concern with CSA remains its propensity to induce renal function impairment. The samples of researches before studying IMN patients treated with CSA were usually small. Few studies had investigated the prognostic factors of the treatment results of CSA in IMN patients.Aims1. Assess the prognostic factors of treatment effect in IMN patients.2. Assess the influence of CSA on remission, relapse and renal function through comparison with other immunosuppressants.3. Study the prognostic factors which can predict remission, relapse and decreased renal function in IMN patients using CSA.4. Study the factors using to distinguish IMN and DN in diabetic mellitus(DM), and to assess the effect of CSA in diabetic patients with IMN.MethodWe retrospectively collected the clinical information of 875 adult patients who were diagnosed as IMN through renal biopsy. The multivariate regression models were used to 1) assess the relationship between CSA and remission, relapse and renal function impairment in IMN patients compared with other immunosuppresants; 2) find out the prognostic factors of remission, relapse and renal function impairment in patients treating with CSA. We also studied the clinical manifestations and treatment effects of IMN against a diabetic background.Result1. There were intotal 875 patients in our study with an average age of 48.2±14.8 years old, of whom 485 were males (55.4%). Over half of these patients were suffered from nephrotic syndrome at baseline. Immunosuppressants were used in 743 patients, including 251 patients who did not reach the diagnostic criteria of NS. Cyclophosphamide(CTX) and CSA were two major immunosuppressive options for IMN patients.789 patients were followed up, with a culmulative remission rate of 81.0%, of them 447 and 192 achieving complete remission(CR) and patial remission(PR), respectively.129 patients relapsed after entering remission, and the estimated glomerular filtration rate(eGFR) of 188 patients had decreased by at least 30% during the follow-up period.2. The relationship between CSA treatment and remission of IMN patients.1) 24-hour urine total protein (24h-UP)>8g was an independent risk factor for failure in achieving CR in IMN patients(OR=0.55, p=0.018) and those treated with CSA(HR=0.33, p=0.003).2) Corticosteroids(OR=3.71, p=0.001) and RASi(OR=2.35, p=0.002) can predict the initial CR in IMN patients.3) Compared with CTX, CSA was not significantly inferior in achieving CR(HR=1.32, p=0.12);4) Reaching PR in the first month is a predictor of further CR in patients treated with CSA(HR=2.76, p=0.004).3. The relationship between CSA treatment and relapse in IMN patients.1) The relapse rates did not differ significantly between pateints treated with CTX and those with CSA(OR=1.50, p=0.21).2) 24-UP>8g was an independent predictor for relapse(OR=2.71, p=0.014).4. The relationship between CSA treatment and descending renal function in IMN patients.1) CSA treatment was an independent risk factor of eGFR decline(OR=4.40, p<0.001).2) Age over 49 years old(HR=4.16, p=0.006) and the duration of CSA treatment exceeding 12 months(HR=3.25, p=0.041) was independently associated with risks of eGFR decrease over 30% at the 24th month.5. The clinical characteristics and treatment of IMN in diabetic mellitus patients.1) eGFR>60.3ml/min/1.73m2 may be an indicator of IMN in diabetic patients suffered from NS.2) No significant difference was found between CSA and CTX treatment in achieving CR in IMN patients with diabetes.3) Compared with those using CTX, IMN patients treated with CSA may be easier to see a 30% decrease in eGFR against the background of diabetic millitus(p=0.009).Conclusion1. We suggest to begin immunosuppressive treatment before 24h-UP reaching 8g because it means poor reaction to treatment and high probability of relapse.2. Corticosteroids and RASi could predict the remission of proteinuria.3. We found that achieving PR in the first month may be a predictor of further CR in patients treated with CSA. Therefore, the declining magnitude of 24h-UP in the first month might be an indicator of treatment effect and adjustment.4. The remission rates and relapse rates did not differ significantly between patients treated with CTX and CSA.5. Using CSA was an independent factor indicating eGFR decreasing by at least 30%. Age over 49 years old and the treatment duration of CSA exceeding 12 months were two prognostic factors of eGFR declining over 30%.