Epidemiology And Outcome Of ANCA Associated Vasculitis

Part I Epidemiology and clinic-pathological characteristics of patients with ANCA associated vasculitisObjective:To analyse the epidemiology and clinic-pathological characteristics of ANCA associated vasculitis (AAV) with renal involvement.Methodology:A retrospective analysis was carried out in 282 patients who were diagnosed as AAV from 1994 to 2013 in the Research Institute of Nephrology, Jinling Hospitial. All patients had renal involvement and renal biopsy. ANCA was detected by both IIF and ELISA methods. All clinical and pathological datas of these patients were collected and analyzed. The risk factors of pulmonary hemorrhage were noted.Results:The male and female ratio was 1:1.29, with the average age 48.6±16.4years. The median duration of disease was 2 months(ranged from 0.2 to 600 months).165 patients (58.5%) were diagnosed within 3 months,57 cases (20.2%) were diagnosed one year after the onset of the disease.Clinical types of AAV included MPA(n=235),GPA(n=22),EGPA(n=14),and RLV(n=11).250(88.6%) patients were MPO-ANCA positive,31(11.0%)patients were PR3-ANCA positive, one patient was double positive. In MPA,91.9% patients was MPO-ANCA positive and 7.7% patients was PR3-ANCA positive.Patients with GPA had both MPO-ANCA(50%)and PR3-ANCA positive(50%).AECA was positive in 29.1% of patients. The most common onset symptoms were renal involvement (33.3%)and general symptom (33%).The extra-renal organs involved included lung(54.0%),nasal(42.9%)joint (19.1%),skin(13.8%),gastrointestinal(7.4%),serositis(5.7%),nerve(4.6%),eye(5.3%), ear (4.3%),muscle(2.5%).90.4% patients had renal dysfunction with an average SCr 4.54±3.13mg/dl, among them,39% required immediate dialysis therapy.24.1% of the patients had gross haematuria and 18.4% had nephrotic proteinuria.Renal biopsy showed crescent formation(91.1%,average38.2±26.4%),glomerular segmental necrosis(66.3%),global sclerosis(average32.3±25.9%).The histopathologic classification was 32(11.3%)focal class,89(31.5%)crescentic class,78(27.7%)mixed class,82(29.1%)sclerotic class, and acute interstitial nephritis in one patient. Patients with pulmonary hemorrhage(n=82) had higher ANCA titres (288.0±298.0 vs 211.7±260.0,P=0.045) and AECA positive ratio (43.8% vs 22.7%,P=0.007) and more severe renal failure [SCr (5.27±3.07) vs (4.24±3.11)mg/dl,P=0.012]than those without pulmonary hemorrhage(n=200). And AECA was a major risk factor for pulmonary hemorrhage(Logistic regression analysis, P<0.05).Conclusion:In this study, the patients were younger and female ratio was higher than those reported by western countries. MPA with MPO-ANCA positive was the most common AAV type, and half of GPA was MPO-ANCA positive. Kidney and lung were the most vulnerable organs. The renal involvement of AAV was severe and the diagnosis establishment was delayed. AECA positive may be related with pulmonary hemorrhage.PartⅡ Clinic-pathological features and outcomes of ANCA associated vasculitis of different typesObjective:To analyse the clinic-pathological features and outcomes of ANCA associated vasculitis of different types.Methodology:A retrospective analysis was carried out in 282 patients [male123,female 159,mean age (48.6±16.4)y] who were diagnosed as AAV with renal involvement.ANCA antigen specificities were determined by enzyme-linked immunosorbent assay(ELISA).According to ANCA antigen specificity, patients were divided into MPO-ANCA group(n=250) and PR3-ANCA group(n=31).Clinical types of AAV included microscopic polyangiitis(MPA,n=235), granulomatosis with polyangiitis(GPA,n=22),eosinophilic granulomatosis with polyangiitis (EGPA,n=14),and renal-limited vasculitis(RLV,n=11).Comparisons were carried out of clinicopathologic manifestations and outcomes of AAV of different types. The renal and patient survival rate and risk factors were noted.Results:(1)Comparison between AAV with correlation to ANCA antigen specificity:The ratio of GPA (35.5% vs 4.4%,P<0.01)and the prevalences of joint (51.6% vs 15.2%,P<0.01)and ear involvement (19.4% vs 2.4%,P<0.01) were significantly higher in PR3-ANCA group than those in MPO-ANCA group. PR3-ANCA group had higher mean value of serum creatinine at the time of diagnosis and the ratio of patients who required immediate dialysis treatment than MPO-ANCA group. (2)Comparison among different clinical types of AAV:14 of 282 patients who were clinically expressed renal limited vasculitis at the time of diagnose, had systemic vasculitis during the follow-up and eventually diagnosed as MPA.Comparison between MPA and RLV showed 91.9% patients of MPA and 100% patients of RLV were MPO-ANCA positive.The age of MPA was slightly older than that of RLV. We found no significant difference in the clinic-pathological features and outcomes of renal vasculitis between MPA and RLV. The mean duration of AAV disease was significantly longer in patients with EGPA than that in MPA、GPA and RLV(P<0.01). The mean duration of renal disease was significantly longer in patients with GPA than that in MPA(15.6±41.0 vs 5.1±13.9,P< 0.01)and RLV(15.6±41.0 vs 2.7±3.5,P<0.05).The prevalences of pulmonary nodules and cavities(27.3% vs 6.8%,P< 0.01)、nasal(72.7% vs 41.7%,P< 0.01) and ear involvement(18.2% vs 3.0%,P<0.01) were higher in patients with GPA than those in patients with MPA. All patients of EGPA had increased peripheral eosinophil ratio and the nerve system involvement in EGPA was significantly higher than that in MPA and GPA.(3) Renal survival:Clinical follow-up was available in 258 patients(1～151 months) and 133 patients were followed more than 1 year(median 40 months). At the end of follow-up,96(34.0%) patients progressed to end stage renal disease and received renal replacement treatment. 1y、3y and 5y renal survival rate was 69.8%、 60.1%、54.3%,respectively. Multivariable Cox regression analysis showed dialysis dependent at diagnosis(HR3.4,P<0.01)、lower serum albumin level(HR 1.1,P<0.01)and pathologic classification(P<0.01)were the risk factors for renal survival,and the patients who presented with focal ANCA-associated glomerulonephritis are at decreased risk for developing ESRD compared with patients who presented with crescentic (HR 8.1,P<0.05) and sclerotic ANCA-associated glomerulonephritis (HR 18.0,P<0.01).The PR3-ANCA group had less favorable renal survival than the MPO-ANCA group(P=0.042).Renal survival rate at 1y、3y and 5y was 72%、61.6%、56.4%in the MPO-ANCA group and 53.7%、47.7%、35.8% in the PR3-ANCA group.There was no difference among MPA、GPA、EGPA and RLV for renal survival. (4)Patient survival:26 patients(9.2%) died during the follow-up,and 21 patients died within ly after the diagnosis.The main cause for death was pulmonary infections(n=14,53.8%).Patient survival rate at 1y、3y and 5y was 89.8%、 85%、 85%,respectively. Multivariable Cox regression analysis showed pulmonary hemorrhage(HR2.56,P<0.05)、higher MPO-ANCA titres (HR1.0,P<0.01)and higher serum creatinine (HR 1.2,P<0.01) were the risk factors for patient survival.Patient survival rate did not differ significantly among different types of AAV(P>0.05).Conclusion:There were significant differences in the clinical and pathological features of AAV of different ANCA types. The low renal and patient survival rate within 1y was the main negative prognostic factor for the long-term survival. The most common cause of death was pulmonary infection. ANCA types had a influence of renal survival,but no influence of patient survival of AAV. Patient and renal survival rate did not differ significantly among different clinical types of AAV.PartⅢ Clinic-pathological features and outcomes of patients with eosinophilic granulomatosis with polyangiitis and renal involvementObjective:To investigate the clinic-pathological features and outcomes of patients with eosinophilic granulomatosis with polyangiitis and renal involvement.Methodology:Fourteen patients diagnosed as eosinophilic granulomatosis with polyangiitis (EGPA)were investigated in this retrospective study. All patients had renal involvement and were performed renal biopsy. Their clinic-pathological features and outcomes were analyzed.Results:They were 8 female and 6 male with age from 20 to 70 years old,and the vasculitis duration from 1～600 months. They accounted for 4.96% of all ANCA associated vasculitis in the same period in our hospital. All patients had positive serum ANCA, among them,12(85.7%)were p-/MPO-ANCA. The most common onset symptom was asthma (57.1%,n=8), the others were hemoptysis (21.4%,n=3)、 gross hematuria(14.3%,n=2)and arthritis (7.14%,n=1). All patients had increased peripheral eosinophil ratio from 10% to 45% with the average 18.1±9.8% accompanied with elevated serum IgE levels of IgE 541±462 g/1. Except one, the other 13 patients had both hematuria and proteinuria. The mean urine protein was 2.90±3.53g/24h,5(35%) had nephrotic syndrome,and 2 had gross haematuria.All patients presented with renal dysfunction with a high level of Scr498.6±288.6umol/l, and 7 patients required initial renal replacement therapy.Renal biopsy showed paci-immune segmental necrotizing glomerulonephritis with crescent formation in 13 patients (6 mixed class,4 crescentic class,2 focal class, and 1 sclerotic class), and acute interstitial nephritis in one.12 patients (85.7%) had eosinophil infiltration in renal interstitium, and 3 showed eosinophil granuloma. All patients received corticosteroid with immunosuppressant therapy.5 patients of those who required initial renal replacement therapy got rid of dialysis, one entered maintenance hemodialysis and one died.12 patients were followed up for 6 to 83 months (median 43.5),2 patients were in completely remission (normal renal function and urine analysis),9 patients progressed to chronic renal failure,one developed to ESRD and one had extra-renal relapse.Conclusion:The renal involvement of eosinophilic granulomatosis with polyangiitis was severe and the renal histological lesions were diverse. Aggressive immunosuppressive therapy could effectively improve renal function, but the overall renal prognosis was poor. Early diagnosis and treatment were needed to improve the long-term renal survival.