| Idiopathic membranous nephropathy (IMN) is a common cause of nephrotic syndrome with onset peak at 40～50 year old patients induced by autoantibody target at podocytes of glomeruli. IMN take 9.89% of primary glomerulonephritis in China. The clinical course of IMN is progress slowly, and is thought to run a more benign course in Asian population. However, there was no persuasive data to show the long-term outcome and prognostic factors of IMN patients in Chinese population. Moreover, the management of IMN patients still be controversial, because of the possibility of spontaneous remission, some investigators believe that the patients should be follow up carefully without immunosuppressive therapy, and some observation showed immunosuppressant improved the prognosis of IMN patients, besides the possibility of severe side effect. In our former observation Tripterygium wilfordii (TW) showed the dramatic effect of reducing the proteinuria of IMN patients, with slight adverse reaction, and the therapeutic effects improved more when combined with steroids. Recent research showed M-type phospholipase A2 receptor (PLA2R) as the major pathogenic antigen in IMN patients, and anti-PLA2R antibody showed a higher positive ratio in patients with massive proteinuria. Thus, we observed the the anti-PLA2R antibody and proteinuria of IMN patients from the baseline to the end of immunosuppressive treatments to discuss the relationship of them. The aim of this study is to investigate the prognosis of IMN in Chinese population and develope the new biomarker and treatment of IMN patients.Part 1. The prognosis and risk factor of idiopathic membranous nephropathy in ChinaObjective:Idiopathic membranous nephropathy (IMN) is a representative form of nephrotic syndrome in China. Although IMN is thought to run a more benign course in Asian than in the Caucasian population, there was no persuasive study to show the long-term prognosis and risk factor of IMN in Chinese populationMethods:A retrospective chart review. All patients admitted to Nanjing Institution of Nephrology from January 1985 to December 2007 with biopsy proven IMN enrolled. The primary outcome was renal survival rate and risk factors at renal biopsyResults:A total of 217 patients were included in the study, the overall renal survival rate was 96.9%,93.5% and 86.6% at 5,10 and 15 years after renal biopsy, respectively. When clinical features at biopsy of were evaluated, patients with hypertension (P=0.023), decreased eGFR (P<0.001), massive proteinuria(P=0.047), elevated urinary NAG(P=0.045) and RBP (P=0.007) had worse prognosis. Cox univariate analysis of clinical and histopathological parameters showed hypertension, decreased eGFR, massive proteinuria, elevated urinary NAG and RBP were clinical risk factors, and chronic tubulointerstitial lesion (HR=3.48, P<0.001) was pathological risk factor for ESRF. Cox multivariate analysis showed decreased eGFR and chronic tubulointerstitial lesion were independent risk factors for ESRF.Conclusion:IMN is a disease with a comparatively good prognosis in Chinese population, with renal survival rate more than 90% at 10 years after renal biopsy. Decreased eGFR at biopsy, chronic tubulointerstitial lesion and persistent massive proteinuria are independent risk factors of ESRF.Part 2. Treatment of membranous nephropathy with tripterygium wilfordii and steroid compared with tarcolimus and steroidObjective:Idiopathic membranous nephropathy (IMN) is a common cause of nephrotic syndrome in adults. Its management is still controversial. A prospective randomized control trial was conducted to evaluate the efficacy of standardized extract of the medicinal plant Tripterygium wilfordii Hook F(TW) combined with steroid(P).Methods:One hundred cases of biopsy-proven IMN were enrolled in this trial, with proteinuria>3.5g/24h. They were randomized divided into two groups, TW+P group:50 patients, TW 2mg/kg, daily for 6 months, and then tapered to maintenance dose of lmg/kg/day for 12 months, and prednisone (0.5 mg/kg/day) for 2 months with taper doses of 10mg alternate-day for 12months. FK+P group:50 patients, FK 2-6mg/d to keep the plasma trough concentration at 4-8ng/ml for 6 months, and then tapered to half for 12 months, the prednisone was same as TW+P group.Results:The probability of PR or CR were 46.1%,58.9%,68.3%, and 77.4% respectively after 1,3,6, and 12 months treatment in TW+P group, While the FK+P group were 14.6%,49%,74.5%, and 77.3%. The CR rates in the TW+P group were 0,2.6%,11.7% and 40.7% after 3,6,12 months and 0,0,14.2%,30.3% in the FK+P group. One patient in TW+P group and three patients in FK+P group had serum creatinine (Scr) doubled during the treatment course. No severe adverse events were observed during the course of treatment.Conclusion:TW+P reduced proteinuria of IMN patients effectively, the partial remission of TW+P may be faster than FK+P, and the complete remission rate at month 12 were higher than FK+P, with less possibility of elevated Scr.Part 3. Relationship of anti- M-type phospholipase A2 receptor antibody and prognosis of proteinuria in patients of idiopathic membranous nephropathyObjective:Anti- M-type phospholipase A2 receptor(PLA2R) antibody is believed to be the major pathogenic antibody of idiopathic membranous nephropathy(IMN). Former researches showed that the positive ratio of anti-PLA2R antibody was significantly higher in IMN patients with nephrotic range proteinuria than remission ones, prompted that the anti-PLA2R antibody was related with the disease activity of IMN patients. Therefore, we observed the anti-PLA2R antibody and proteinuria of IMN patients continuously from the baseline to the course of immunosuppressive treatments to discuss the relationship of them.Methods:IMN patients proved by renal pathology with massive proteinuria (>3.5g/24hr) were enrolled. All patients received Tripterygium wilfordii and steroid(TW+P) or tacrolimus and steroid (FK+P). Anti-PLA2R antibody and proteinuria were recorded at baseline,6 month and 12 month.Result:There were 13 patients enrolled, Anti-PLA2R antibody of 4 patients among them turned negative during the immunosuppressive treatment, the proteinuria of them also got partial or complete remission. 6 of these patients’antibody kept positive all along the treatment course, whose proteinuria persisted. Anti-PLA2R antibody of other 3 patients were once turned negative but was positive again at month 12,after the decrement of immunosupprensants. At month 12, the patients without anti-PLA2R antibody got high remission of proteinuria than positive ones(0.51±0.19 vs 5.67±2.32 g/24hr, p<0.001).Conclusion:The anti-PLA2R antibody correlate with the autoimmune reaction of IMN patients, promote the needs of immunosuppresion therapy, and it correlated significantly with the proteinuria of IMN patients, reflect the acitivty of disease. |
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