Clinical And Pathological Features In Pauci-immune Crescentic Glomerulonephritis Patients

Objective: The incidence of ANCA negat ive PICGN was reported to be higher in Chinese patients. In this study, to compare the clinicopatholoical pictures and outcomes in patients with ANCA positive and ANCA negative pauci-immune crescentic glomerulonephritis(PICGN).Methodology: 75 Chinese PICGN patients (27 males and 48 females) proved by clinical and renal biopsy were enrolled in this study. ANCAs were detected with both standard indirect immanofluorescence (IIF) assay and ELISA for MPO-ANCA and PR3-ANCA. The patients were divided into ANCA positive (ANCA+) and ANCA negative (ANCA-) groups. Serum anti-GBM anti-body and ANA were also detected with IIF assay.Results: ANCA was positive in 45 of 75 patients (60.0 %). Anti-GBM antibody was negative in both groups. Comparing with ANCA -, the cases of ANCA + manifested with older age (51.7±13.7y vs 44.3±14.1, P =0.028), no difference in duration of disease (5.8±8.5m vs6.5±6.7 m) and gender (14M/31F vs 13M/17F). Clinically,renal disfunction, anaemia, hypertension, haematuria, proteinuria were noticeable clinical characteristics of PICGN both ANCA+ and ANCA- group. Compared with the patients in ANCA+ PICGN group, patients with positive ANCA had higher level of urinary protein (3.7 vs. 2.4g/d,p=0.045), higher prevalence of nephrotic syndrome (40.0% vs. 15. 6%,p=0.017) and gross hematuria (56.7% vs. 31.1%, p=0.028). However less ANCA- PICGN patients suffered from empsyxis or invasion pulmonary changes (20.8%vs 52.8%,p=0.013)than those with ANCA+. pathological, the characteristic changes of vasculitis, such as capillary necrosis(58.3%vs 66.7%) , interstitial vasculitis(58.3%vs 50.0%), eosinophilic granulocyte infiltration (55.6%vs 70.8%) were found similarly in ANCA+ and ANCA- PICGN patients while the degree of crescent formation (77.8 vs. 63.5%,p<0.001 ) and were markedly higher in ANCA+ than that in ANCA- PICGN patients. Among glomeruli with crescent formation, the percentage of fibrous crescent tended to be higher in patients with ANCA+. Death rate was 26.6% in ANCA+ group while none in ANCA- group. Until the end of our follow up, the patients with ANCA+ and ANCA- received a median follow up 40 (range 6-120) and 49 (range 7-144) months. The 5 years renal survival cumulative proportion of patients with ANCA+ and ANCA- was 37.5% and 61.5%, respectively.Conclusion: This study showed that patients with ANCA + and ANCA - PICGN had many markedly differences in clinical manifestations, renal histological lesions and prognosis. It may be the different characteristics that more nephrotic syndrome and gross hematuriathe, but less extrarenal involvement, milder renal insufficiency, less chronic lesions, and better outcomes were more common in paitents with ANCA- PICGN. ANCA- PICGN might represent an independent disease entity from ANCA+ PICGN. STUDY TWO Effects of mycophenolate mofetil versus pulse cyclophosphamide therapy in patients with pauci-immune crescentic gomerulonephritisObjective: To compare the effect, relapse rate and outcomes between mycophenolate mofetil (MMF) and pulse intravenous cyclophosphamide (CTX) in the induction therapy of in Chinese patients with pauci-immune crescentic gomerulonephritis (PICGN).Methodology: Forty-four patients who had PICGN [16 male, 28 female, age (46.8±13.7) y], of whom 25 patients were ANCA positive, were investigated in this study. All patients had renal involvement with≥50% crescent formation prior to the study and were received either MMF treatment (MMF group, n=22) or intermittent CTX pulse therapy (CTX group, n=22). The patients in both groups also received methylprednisolone (MP) pulse therapy followed by oral prednisone. The general conditions, clinicopathological findings, remission rate, relapse rate, and outcomes were compared in both groups. All the patients were followed up until June 2005, with an average follow up in the MMF group for range 8～60 (Med 27) months, and range 6～72 (Med 29) months in the CTX group.Results: No significant difference was found between MMF group and CTX group in general conditions, base parameters of clinical and pathological findings. The remission rate at the 12th month in MMF and CTX group were 90.9% and 72.7%. The complete remission rate in MMF group (59.1%) was significantly higher than that of the CTX group (27.3%) (p=0.003). Furthermore, 3 of the 13 ANCA positive patients (23.7%) in the MMF group and none of the 12 patients in the CTX group were ANCA negative after 12 months treatment. The relapse rate in MMF group (4.5%) was lower than that of the CTX group (23.5%). However, the side effect of infection was more significant in the MMF group (22.7%) than in the CTX group (4.5%).Conclusion: MMF was more effective than intermittent CTX pulse therapy in inducing remission, improving renal function and reducing relapse rate in patients with PICGN, although potentially associated with a higher infection rate.