Limited Vasculitis Research Articles

Clinical characteristics and prognostic factors for MPO-ANCA positive interstitial lung disease: A comparative study of ANCA associated vasculitis (AAV)-ILD and pulmonary limited vasculitis.

Microscopic polyangiitis (MPA) with interstitial lung disease (ILD) has a significant impact on morbidity and mortality. This study evaluated the clinical characteristics, treatment responses, and prognostic factors of patients with ANCA-associated vasculitis with ILD (AAV-ILD) and pulmonary limited vasculitis (PLV). A retrospective chart review of ILD patients positive for MPO-ANCA was conducted from 2008 to 2021. Patients were classified into AAV-ILD or PLV groups. Data included laboratory test results, pulmonary function tests, and high-resolution computed tomography (HRCT) images. Statistical analyses were used to assess group differences and survival outcomes. Of 114 patients, 80 were diagnosed with PLV and 34 with AAV-ILD. The AAV-ILD group had higher corticosteroid treatment rates, higher serum creatinine levels, and better survival than the PLV group. The PLV group had higher KL-6 levels, lower %VC and % FVC in pulmonary function tests. Survival in the PLV group was significantly worse than that in the AAV-ILD group, and survival of patients with an alternative diagnosis on HRCT was better than that of patients with a UIP pattern. Cox regression analysis identified a diagnosis of MPA and HRCT classification as significant prognostic factors. Patients with AAV-ILD had a better prognosis than those with PLV. HRCT patterns, particularly an alternative diagnosis on HRCT, were associated significantly with a favourable prognosis. The efficacy of corticosteroid treatment in PLV patients was limited. These findings highlight the importance of early and accurate diagnosis, as well as careful consideration of treatment strategies, for patients with in MPO-ANCA-positive ILD.

Muscle vasculitis in patients with polymyalgia rheumatica; three case series.

Polymyalgia rheumatica (PMR) is a common inflammatory disorder characterized by myalgia/stiffness in proximal hip and shoulder girdle, elevated C reactive protein (CRP) and erythrocyte sedimentation rate (ESR), but its pathogenesis is not fully elucidated. We report three cases of PMR who do not respond adequately to standard treatment. Those patients had typical symptoms of myalgia and muscle weakness, with elevated CRP in absence of creatine kinase elevation. Muscle specimen showed the findings of vasculitis in all cases, therefore muscular limited vasculitis (MLV) may be an underlying pathology in PMR in those refractory cases.

Myeloperoxidase-ANCA IgG induces different forms of small vessel vasculitis based on type of synergistic immune stimuli

Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis has diverse patterns of injury including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Necrotizing and crescentic glomerulonephritis (NCGN) occurs in all syndromes and as renal limited vasculitis (RLV). Single dose intravenous ANCA IgG-specific for mouse myeloperoxidase (MPO) causes RLV in mice. Although multiple mouse models have elucidated ANCA-IgG induced necrotizing and crescentic glomerulonephritis (NCGN), pathogenesis of ANCA-induced granulomatosis and vasculitis outside the kidney has not been clarified. To investigate this, we used intravenous MPO-ANCA IgG in the same strain of mice to induce different patterns of lung disease mirroring patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Repeated intravenous MPO-ANCA IgG induced GPA with NCGN, lung capillaritis, arteritis and granulomatosis. Lung leukocyte phenotypes were evaluated by immunohistochemical image analysis and by flow cytometry. ANCA lung capillaritis and microabscesses began within one day and evolved into granulomas in under seven days. Influenza plus single dose MPO-ANCA IgG induced MPA with NCGN, lung capillaritis and arteritis, but no granulomatosis. Allergic airway disease caused by house dust mites or ovalbumin plus single dose intravenous MPO-ANCA IgG induced EGPA with eosinophilic bronchiolitis, NCGN, capillaritis, arteritis, and granulomatosis. Thus, our study shows that the occurrence and pattern of lung lesions are determined by the same ANCA IgG accompanied by different synergistic immune factors.

A case of renal limited myeloperoxidase anti-neutrophil cytoplasmic antibody-positive vasculitis treated with maintenance avacopan monotherapy.

A 76-year-old woman was admitted with progressive renal function decline. A kidney biopsy was performed because of myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA; 333IU/mL), proteinuria (1.21g/d), and urinary erythrocyte sediment (10-19/high-power field). Renal-limited ANCA-positive vasculitis with pauci-immune necrotizing crescentic glomerulonephritis (ANCA-associated vasculitis, AAV) was diagnosed. Glucocorticoid therapy was started, and the patient responded well. About 1year later, avacopan treatment was started and glucocorticoid therapy was discontinued. Avacopan did not normalize ANCA levels and did not make urinary findings negative. However, further progression of renal function decline is prevented. Factors attributed to the development of AAV in this case were investigated; AAV developed after the second dose of the COVID-19 vaccine and ANCA levels re-elevated after the fifth dose. This suggests that the COVID-19 vaccine may have contributed to the development of AAV in this elderly patient. Avacopan monotherapy has been shown to be effective as maintenance therapy to control the progression of renal failure although not sufficient for complete remission of AAV.

#1782 Clinicopathological study of renal limited pauci-immune vasculitis and its short-term outcome: a single centre observational study

Abstract Background and Aims Pauci immune crescentic glomerulonephritis, is a leading cause of RPGN. The majority of patients with PICGN have glomerular diseases as a part of a systemic small vessel vasculitis, a minority may present as renal-limited vasculitis. In north-east India, there are still no major studies in this group of patients. Therefore, our study involving north-east Indian population constitutes an effort to prospectively study the clinico-pathological feature of patients with PICGN and assess the short-term outcome. Method This single-centre, prospective, observational, study was conducted over 12 months at the Department of Nephrology, Gauhati Medical College. All renal biopsy-proven patients with pauci-immune renal vasculitis were included, excluding those with secondary vasculitis. Baseline characteristics and laboratory data were recorded, and disease activity was assessed using the Birmingham Vasculitis Activity Score. The ANCA tests were performed using a standardised essay for both indirect immunofluorescence assay and antigen-specific ELISA. The renal biopsy specimen obtained was evaluated by light microscopy and direct immunofluorescence. The sample size was calculated based on the prevalence of pauci-immune glomerulonephritis, and data were analysed using SPSS. Results The study involved 24 patients, predominantly females (70.83%), aged 14-65 years, presenting predominantly with pedal oedema and oliguria. Laboratory findings showed varying levels of haemoglobin, total count, platelet count, creatinine, and 24-hour urine protein. 50% of the patients were (MPO) positive, 33.3% were (PR3) positive while 16% were ANCA negative. Renal biopsy analysis showed a majority with mixed class according to the Berden classification. Treatment involved induction with Methylprednisolone and Cyclophosphamide, with dialysis administered to 58.3% of patients. At six months, 36.3% had a stable GFR, and 50% were on maintenance hemodialysis. Factors predicting renal loss included oliguria, dialysis at presentation, and fibrous/fibrocellular crescents. The best predictor of renal outcome was serum creatinine at presentation. Conclusion Pauci-immune CrGN is a severe disease affecting a wide age range. Early diagnosis and treatment initiation are crucial for better outcomes, including lower ESRD risk and relapse rates. Prognostic factors include baseline serum creatinine levels and fibrous crescents. Optimising treatment regimens may improves outcomes.

#2291 ANCA negative vasculitis—the unmet need within small vessel vasculitis

Abstract Background and Aims ANCA negative small vessel vasculitis with renal involvement has been described in a number of cohorts. Though comprehensive studies comparing these individuals to ANCA positive patients are lacking and they are routinely excluded from clinical trials. Whilst the numbers are smaller than those with ANCA positivity, they still make up a large proportion of small vessel vasculitidies (Fig. 1). The absence of detectable circulating ANCA is thought to indicate a distinct spectrum of the disease. There remains unanswered questions regarding the pathophysiology, diagnosis and management of patients with seronegative AAGN. We present data from Croatian referral center. Method Study included 106 AAV patients with biopsy proven renal involvement in the period from 2007-2017. Category variables were analysed with Fisher Exact test and continuous with Kruskal-Wallis test. Statistical difference was then analysed post hoc with Chi-square test. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between clinical phenotypes and finding significant predictors regarding outcomes which were defined as combined outcome end-stage renal disease and death (ESRDD), ESRD alone, the death outcome alone and relapse rate. Results 106 AAV patients with renal involvement were included: 66 (61.1%) MPA, 20 (18.5%) GPA, 20 (18.5%) RLV. 14 (13%) were PR3-ANCA positive, 57 (52.8%) MPO ANCA positive, 5 (4.6%) PR3-ANCA+MPO-ANCA and 32 (29.6%) ANCA negative patients. ANCA negative patients were comparatively younger (p = 0.02) and presented with more renal limited vasculitis (RLV; p < 0.001), lower BVAS (p = 0.003) and lower CRP (p = 0.001). ANCA negative patients usually presented with nephrotic syndrome compared to positive ones which presented with rapid progressive nephritic syndrome or acute nephritic syndrome (p = 0.027). 24-hour proteinuria levels were higher in ANCA negative group (p = 0.003). Though statistical difference was not reached, there was tendency for ANCA negatives to receive less plasmapheresis (p = 0.074). Histologically there were no differences between ANCA positive and ANCA-negative patients. On sub analysis ANCA negatives versus individual seropositive groups, there was tendency that ANCA negatives and MPO-ANCA patients had lower percentage of glomerular crescents (p = 0.092) but more acute tubular damage (p = 0.087). There were no differences in clinical outcomes between the groups. Conclusion ANCA negative vasculitis form a large proportion of small vessel vasculitidies and present with different clinical laboratory and histological (renal) characteristics than ANCA positive ones. More often than not disease seems to be renal limited and patients tend to be younger. Due to the rarity of the disease, there remains unanswered questions regarding the pathophysiology, diagnosis and management of these patients. This study highlights noteworthy distinctions between the two groups. Whether these differences warrant adjustments in treatment algorithms or a reconsideration of the classification of small vessel vasculitis remains to be determined. Further investigation into the pathogenetic mechanisms of seronegative AAVs is essential.

403 Kidney limited ANCA-associated vasculitis in a patient with persistently positive PR3 autoantibodies 1 year prior to biopsy confirmation

403 Kidney limited ANCA-associated vasculitis in a patient with persistently positive PR3 autoantibodies 1 year prior to biopsy confirmation

Renal Limited Anti-Neutrophil Cytoplasmic Antibody Associated Vasculitis: A Case Report

Background: Renal Limited Vasculitis (RLV) is a localized autoimmune vascular inflammatory disorder that is part of the Pauci Immune Glomerulonephritis (PIGN) spectrum. Over 90% of PIGN patients have circulating Anti-Neutrophil Cytoplasmic Antibodies (ANCA Ab). Anti-Neutrophil Cytoplasmic Antibody (ANCA) associated vasculitides are a heterogeneous group of multisystemic autoimmune disorders with distinct pathological findings. They are characterized by widespread inflammation of vessels according to their size, their location, and their serotypes based on the presence or absence of ANCA antibodies, namely Myeloperoxidase (MPO-ANCA), Proteinase-3 (PR3-ANCA) or simply ANCA negative, if no antibodies are found. RLV is characterized by antibody positivity to myeloperoxidase in the majority of cases. Case Report: A 77-year-old Caucasian female was admitted with altered mental status and laboratory evidence of renal function compromise consistent with non-oliguric acute renal failure. Imaging and renal biopsy resulted in a diagnosis of pauci-immune glomerulonephritis consistent with MPO-ANCA vasculitis with a subtype that was associated with necrotizing arteritis, a severe form of the disease. She was placed on hemodialysis, intravenous cyclophosphamide, and oral prednisone, and entered remission. Conclusion: A high level of suspicion and familiarity with clinical signs and symptoms are critical in distinguishing primary RPGN subtypes from other types of ANCA-associated small vessel vasculitis. If left untreated, renal limited vasculitis can progress to widespread systemic involvement and become fatal.

#6407 RENAL LIMITED VASCULITIS: DATA FROM A CROATION REFERRAL CENTER

Abstract Background and Aims Small vessel vasculitis and in particular ANCA associated vasculitis (AAV) are diseases with variable clinical presentation. Renal limited vasculitis (RLV) can vary in presentation and characteristics compared to systemic disease. There is a tendency to categorise RLV as a part of microscopic polyangiitis (MPA) spectrum though there seem to be differences in terms of both histology and serology between RLV and MPA. We present data on patients with renal limited vasculitis from our referral center. Method This study included 106 consecutive AAV patients with biopsy proven renal involvement in the period from 2007-2017. Category variables were analysed with Fisher Exact testom and continuous with Kruskal-Wallis testom. Statistical difference was then analysed posthoc with Chi-square test. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between clinical phenotypes and finding significant predictors regarding outcomes which were defined as combined outcome end-stage renal disease and death (ESRDD), ESRD alone, the death outcome alone and relapse rate. Results Out of 106 AAV patients with renal involvement in our database: 66 (61,1%) MPA, 20 (18,5%) GPA (granulomatosis with polyangiitis), 20 (18,5%) RLV. In RLV group 14 (70%) were female and average age was 55 (IQR 47-60). Average SCr in RLV group was 234 μmol/l (IQR 168-376,5) and median proteinuria was 3,3g/24h (IQR 0,9-3,8) and most of these patients presented with either nephrotic syndrome (30%) or RPGN (30%). Serologicaly 90% of RLV patients were ANCA negative and 10% were MPO-ANCA positive. Histologicaly (Berden classification) 60% had mixed class, 25% crescentic, 10% focal and 1% sclerotic. Average BVAS score was 14 (IQR 12-17). Compared to MPA and GPA, RLV patients were younger (p=0,058), had less expressed constitutional symptoms (p= 0,013) with lower average BVAS (p=0,0001) and lower CRP levels (p=0,001). Though there was no significant difference of average SCr level RLV patients presented more often with nephrotic syndrome (p=0,014), had histological predominantly mixed class (p=0,006) and higher interstitial fibrosis and tubular atrophy (IFTA) percentage (p=0,086). Interestingly, compared to MPA and GPA majority of RLV patients were ANCA negative (p=0,001). There were no statistically significant differences in treatment used both in induction (including need for dialysis and/or PLEX) or remission maintenance treatment between RLV, MPO and GPA group. In survival analysis there was no statistical differences for all of the outcomes between RLV group, MPA and GPA group. Conclusion RLV can be challenging disease considering it's clinical presentation but also characteristics of renal involvement in terms of more often nephrotic proteinuria and higher IFTA percentage. This might suggest that these patients could have slower disease course (so called slower progressors). Also interestingly in our cohort most of these patients were ANCA negative which also makes diagnosis predominantly a combination of clinical presentation and histology thus prompting a question of how should we classify RLV within a spectrum of small vessel vasculitis. More research is needed to better understand the RLV.

Monitoring disease activity in antineutrophil antibody-associated vasculitis.

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises a group of multisystem disorders with alternating periods of relapse and remission. Beyond that, a smouldering progress during apparently clinically silent phases often develops. AAVs are subgrouped in microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and renal limited vasculitis (RLV). ANCA are hallmark of this disease entity, although they are not always present. Despite the simplification of treatment, fundamental aspects concerning assessment of its efficacy and its adaptation to encountered complications or to the relapsing/remitting/subclinical disease course remain still unknown. Through the advances in pathogenesis and pathophysiology of AAV a reliable biomarker-based monitoring and treatment algorithm has not been established and disease management follows not infrequently a "trial and error" approach. Here, we overviewed the most interesting biomarkers reported so far.

Renal Limited PR3-ANCA Vasculitis due to Abiotrophia defectiva Infective Endocarditis

Renal Limited PR3-ANCA Vasculitis due to Abiotrophia defectiva Infective Endocarditis

Dialysis Dependency at Discharge in De Novo ANCA Associated Renal Limited Vasculitis: Should We Avoid Further Immunosuppression?

Introduction: ANCA associated vasculitis commonly affects the kidneys. The intense inflammatory damage disrupts the glomerular architecture. Induction immunosuppressive therapy is responsible for a large part of the morbidity and mortality of these patients, due to infectious complications. This highlights the importance of defining risk factors associated with a worse renal prognosis in order to select the patients who would benefit the most from immunosuppressive therapy when it comes to renal limited vasculitis. Methods: Retrospective collection of data from patients admitted to the Coimbra’s University Hospital Nephrology Department with the diagnosis of de novo ANCA vasculitis, between 01-06-2009 and 01-06-2019. Data were analysed with SPSS v26® using parametric and nonparametric tests, Kaplan Meyer survival and ROC curve analysis. Results: There were 81 cases of de novo vasculitis, mainly due to anti-MPO antibody associated vasculitis (N=69; 85.2%). Mean age at diagnosis was 67.4 ± 15.7 years and most patients were male (N=47; 58%). At admission, patients had a mean serum creatinine (sCr) of 6.8 ± 4.0 mg/dL. Dialysis was required in 23 (28.4%) patients at admission and 44.4% were dependent on renal replacement therapy at discharge. Among dialysis-dependent patients at discharge treated with immunosuppression for at least 3 months (N=15) we observed partial kidney recovery in 2 (13.3%). Deaths were mostly (N=8/11; 72.7%) caused by infections. Discussion: Our results call into question the need for aggressive induction treatment in dialysis-dependent patients without extrarenal manifestations.

MO134: Follow-Up of Patients with Vasculitis: A 10-year retrospective study

Abstract BACKGROUND AND AIMS Vasculitis constitutes a systemic disease with renal involvement at almost 100% in microscopic polyangiitis, 70–80% in granulomatosis with polyangitiis, 25% in eosinophilic granulomatosis with polyangitiis and 40–50% appears as renal limited vasculitis. In order to describe our experience, we conducted a retrospective study of patients with vasculitis which we have been monitoring for the last 10 years. METHOD We studied the time of the remission, the use of plasma exchange (PLEX), the biopsy results as well as the time between the first symptoms and the initiation of the therapy. RESULTS The total number of patients was 59, 28 (47.5%) females, with a mean age of 66.08 ± 13.95 years. The median follow-up time was 70 weeks with IQR [64, 76]. The patients with positive pANCA/MPO were 38 (64.4%), while those with positive cANCA/PR3 were 10 (16.9%). The remaining nine patients (15.3%) suffered from ANCA negative vasculitis. The mean value of the initial creatinine was 4.53 ± 2.3 mg/dL and the median value of the eGFR CKD-EPI was 11 mL/min/1.73 m2, IQR [7, 17]. The PLEX was implemented auxiliary in 16 patients (27.1%) and in 32 patients (54.2%) pulse cortisone along with intravenous cyclophosphamide was preferred. The remission was accomplished in 32 patients (54.2%) with median time of 8 weeks, IQR [0, 17]. At least one relapse episode was noted in 8 patients (13.6%), 19 patients (32.2%) ended up in ESRD and 15 patients (25.4%) deceased during the follow-up time. The major cause of death was sepsis with 10 demises (66.7%), while 5 patients (8.4%) suffered from malignancies in general. The remission time was found to be dependent on the initial value of creatinine (P-value.023). There was no statistical significance regarding the findings of the biopsy and the outcome, the relapse rate or the remission time. There was also no correlation marked between the first symptoms and the initiation of the therapy. The plasma exchange failed to reduce the time until the remission, unless the patient was cANCA positive (P-value.036). Although the sample was limited, the patients with positive cANCA/PR3 submitted to PLEX were able to achieve the remission in 5.25 weeks contrary to those who received solely methylprednisolone and cyclophosmamide. The latter achieved remission in 21 (mean) weeks (LogRank test, P-vaue .001. The vasculitis type has no effect over the renal outcome or the relapse rate. No statistical significance was found between the PLEX and the relapse rate or the outcome. Patients do not benefit from auxiliary treatment with the PLEX, unless they have positive cANCA/PR3. However, the initial serum creatinine seems to affect the time of the remission. CONCLUSION There is indisputable need for a larger patient sample in order to safely conduct further results.

CNS limited ANCA-associated vasculitis presenting as an isolated intraparenchymal mass

The authors report a 34-year-old male with antineutrophil cytoplasmic autoantibody (ANCA) associated vasculitis (AAV) which only involved the central nervous system and presented with an isolated mass in the left parietal lobe. Constitutional symptoms were lacking and the only symptom was progressive right-sided hemiparesis. Pathology suggested necrotizing vasculitis without eosinophils and granulomas. Cytoplasmic ANCA was elevated to 103.9 IU/ml (>5 times the upper limit) in serum. He obtained a regression following treatment of cyclophosphamide and steroids. Prompt diagnosis of AAV is essential since early and aggressive initiation of immunosuppressive therapy can avoid further neurological sequelae.

Prevalence of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Spatial Association With Quarries in a Region of Northeastern France: A Capture-Recapture and Geospatial Analysis.

Silica is an environmental substance strongly linked with autoimmunity. The aim of this study was to assess the prevalence of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and renal limited vasculitis, in a northeastern region of France and to evaluate whether there was a geospatial association between the localization of quarries in the region and the prevalence of these AAVs. Potential AAV patients were identified using 3 sources: hospital records, immunology laboratories, and the French National Health Insurance System. Patients who resided in the Alsace region of France as of January 1, 2016 and who fulfilled the American College of Rheumatology criteria for GPA or the 2012 Chapel Hill Consensus Conference definitions for GPA or MPA were included. Incomplete case ascertainment was corrected using a capture-recapture analysis. The spatial association between the number of cases and the presence of quarries in each administrative entity was assessed using regression analyses weighted for geographic region. Among 910 potential AAV patients, we identified 185 patients fulfilling inclusion criteria: 120 patients with GPA, 35 patients with MPA, and 30 patients with renal limited vasculitis. The number of cases missed by any source as estimated by capture-recapture analysis was 6.4 (95% confidence interval [95% CI] 3.6-11.5). Accordingly, the estimated prevalence in Alsace in 2016 was 65.5 GPA cases per million inhabitants (95% CI 47.3-93.0), 19.1 MPA cases per million inhabitants (95% CI 11.3-34.3), and 16.8 renal limited vasculitis cases per million inhabitants (95% CI 8.7-35.2). The risk of AAV was significantly increased in communities with quarries (odds ratio 2.51 [95% CI 1.66-3.80]), and geographic-weighted regression analyses revealed a significant spatial association between the proximity to quarries and the number of GPA cases (P = 0.039). In analyses stratifying the AAV patients by ANCA serotype, a significant association between the presence of quarries and positivity for both proteinase 3 ANCAs (P = 0.04) and myeloperoxidase ANCAs (P = 0.03) was observed. In a region with a high density of quarries, the spatial association between the presence of and proximity to quarries and the prevalence of AAVs supports the idea that silica may have a role as a specific environmental factor in this disease.

“Triple-positive” renal limited vasculitis presenting with rapidly progressive glomerulonephritis

Rationale: Coexistence of anti-glomerular basement membrane (anti-GBM) disease with anti-neutrophil cytoplasmic antibody (ANCA) in a case of glomerulonephritis is often identified as a “double-positive” disease. Interestingly, the majority of “double positive” ANCA is myeloperoxidase (MPO)-ANCA and some of the MPO-ANCA positive cases showed intrarenal arteritis, suggesting an ANCA-associated kidney lesion. Proteinase 3-ANCA positive diseases are also rarely reported. Patients positive for all three antibodies, i.e., triple-positive patients, are extremely rare. Patient's Concern: A 53 year-old female presented with anasarca and oliguria of 2 months’ duration. Diagnosis: Pauci-immune type renal limited crescentic glomerulonephritis positive for MPO-ANCA, proteinase 3-ANCA, and anti-GBM antibody (triple-positive). Interventions: Intravenous high dose cyclophosphamide, oral azathioprine, intravenous methylprednisolone, and plasma exchange as per British Health Professionals in Rheumatology Guidelines. Outcomes: After one-month follow-up, anasarca and proteinuria were lessened, serum creatinine was normalized, titers of MPO-ANCA levels were decreased, and anti-GBM antibody levels were normalized. Lessons: Triple-positive renal limited vasculitis is rare and response to combined immunosuppressive therapy and plasma exchange can contribute to successful remission.

MO004THE SAFETY PROFILE OF REPEAT RITUXIMAB TREATMENT IN ANCA-ASSOCIATED VASCULITIS - A 10 YEAR SINGLE CENTRE STUDY

Abstract Background and Aims Rituximab is a proven effective induction and remission-maintenance treatment in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Studies have identified hypogammaglobulinemia, infection, and late-onset neutropenia as potential adverse events. There is limited data on long-term outcomes following extended periods of B-cell depletion therapy with rituximab in AAV cohorts. We conducted a retrospective study to examine the safety profile of repeated rituximab treatment in AAV. Method All patients with AAV treated with rituximab between 1st January 2008 and 31st December 2018 were identified through local dispensary database. Patients were stratified into low (≤4g), medium (>4g to ≤8g) and high (>8g) dose groups according to the cumulative rituximab dose received until 1st October 2019. Baseline characteristics and events including death, opportunistic and severe infections (defined as infections required hospitalization and/or intravenous antibiotic administration), neutropenia (neutrophil count ≤1.5x109/L), hypogammaglobulinemia (IgG level≤5.0), infusion reactions and malignancy diagnosed post-rituximab treatment were examined and compared between the groups. Results 364 patients (49% male, 52 year old mean age) received rituximab for treatment of active disease or remission maintenance. 49%(n=175) had repeat rituximab treatments (267/513 treatment courses for relapsing disease and 247/513 for remission maintenance). There were 262 (72%), 70(19%) and 32(9%) patients in low-, medium- and high-dose groups respectively. The median cumulative rituximab dose for each group was 2g, 6g and 12g (p<0.001). Low-dose group patients were older (59 and 40 years, p<0.001) and more likely to have renal-limited disease compared to high-dose groups (19%vs4%; p<0.05). Conversely, there were more ear-nose-throat (ENT) /ocular limited (41% and 13%; p<0.05) and antiproteinase 3 (PR3)-ANCA positive disease (56% vs 38%, p<0.05) in high-dose compared to low-dose group. The overall median duration of follow up was 72 months (QR: 28-135months)(Table1). Outcomes (Table2): Infections: no difference in serious or opportunistic infection rate between groups (1.2 vs 0.1 vs 0.1infections/patient/year; p=0.18). 77% of opportunistic infections across all groups were related to herpesvirus (e.g. Cytomegalovirus/Herpes Zoster/Herpes Simplex) reactivation. Hypogammaglobulinemia: incidence was comparable between groups (9.7% vs 10% vs 9%, p=0.91). Overall median time to event was 5 months from first rituximab. Neutropenia: 101 patients had recorded neutropenia after rituximab (Low-dose: 32%; medium-dose 16% and High-dose: 22%, p<0.05). All were related to concurrent immunosuppressants (e.g. Azathioprine, cyclophosphamide or mycophenolate) or infection. Events resolved after withdrawal or reduction of concurrent immunosuppressant or treatment of underlying infection. Cancer: No difference in malignancy rate between groups (6% vs 14% vs 3%, p=0.22). 39 malignancies reported in 32 patients post rituximab treatment. The two commonest reported cancers were skin (36%) and breast cancer (21%) Deaths: 58 patients died during the study period. Mortality rate in the low and medium-dose groups were comparable (82% survival at 30 month after last rituximab). Conversely, there were no deaths in the high-dose group. Conclusion In this large, single-centre cohort of patients with AAV, we did not observe an increased incidence of adverse events with increasing cumulative rituximab exposure. This likely reflects physician bias in patient selection for repeat treatment and suggests that in selected patients, extended periods of rituximab treatment might be safe. The superior survival seen in high-dose group was likely related to higher proportion of ENT/ocular limited vasculitis.

P0471DIALYSIS TREATMENT AT THE TIME OF DIAGNOSIS PREDICTS OUTCOMES IN ANCA ASSOCIATED VASCULITIS PATIENTS - DATA FROM CROATIAN REFERRAL CENTER

Abstract Background and Aims Dialysis dependence and ESRD are known complications of ANCA associated vasculitis (AAV) with renal involvement. What is not so often discussed is the role of dialysis treatment at the time of diagnosis and how it affects patient outcomes as well as characteristics of such patients. We present data showing the importance of dialysis treatment at the time of diagnosis as the predictor of clinical outcomes. Method This study included 106 consecutive AAV patients with renal involvement in the period from 2007-2017. We performed renal biopsy on patients using automatic 16 Gauge needle. Light, immunofluorescent and electronic microscopy were performed. Primary outcomes were combined outcome progression to end-stage renal disease, defined as persistent (more than three months) need for renal replacement therapy or permanent reduction of EGFR to <15ml/minute (according to CKD EPI formula) and/or death (ESRDD), death (D) and ESRD alone, and disease relapse. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between phenotypes and finding significant predictors regarding outcomes. Results Out of 106 patients (55,6% female, median age 61; IQR 51-70) there were 66 (61,1%) microscopic poliangitiis (MPA), 20 (18,5%) granulomatosis with angitiis and 20 (18,5%) with renal limited vasculitis (RLV). Out of those 14 (13%) were PR3-ANCA positive patients, 57 (52,8%) MPO ANCA positive, 5 (4,6%) PR3-ANCA+MPO-ANCA positive and 32 (29,6%) ANCA negative patients. Average serum creatinine (SCr) levels was 316,5 μmol/l (IQR 207,0-548,5), 24-hour proteinuria median was 1,7g/24h (IQR 0,8-2,8). According to the Berden classification 43 (39,8%) patients had crescentic, 19 (17,6%) focal, 34 (31,5%) mixed and 12 (11,1%) sclerotic class. Follow up time ranged from 1 to 127 months. Median follow up time was 21 months (IQR = 7-44). Median time to diagnosis was 3 months (IQR 2,0-6,0). Patients requiring dialysis treatment at the time of diagnosis were more often MPO – (p=0,04), had more severe anemia (p=0,001), higher CRP (p=0,003), and more pronounced hypoalbuminemia (serums albumin <30g/l; p=0,006).Such patients were older than those not requiring dialysis (p=0,055) na had shorter time to diagnosis (p=0,001). Clinically such patient s presented more often with RPGN (p<0,001) which is in a way expected thus having higher SCr levels (p=<0,001). Histologically dialysis treated patients predominantly had crescentic class, while non-dialysis group had focal class (p<0,001). Of note dialysis group had more acute tubular damage (p=0,007). Interestingly enough there was slightly more positive C3 deposition in dialysis group (p=0,09). In univariate analysis the need for acute dialysis at the time of diagnosis of AAV was significant predictor for combined ESRDD, D, ESRD and relapse rate. In multivariate analysis the need for acute dialysis at the time of diagnosis of AAV remained significant predictor for ESRD (HR = 4,674, 95% CI =1,996-10,946; p = < 0,001) and relapse rate (HR = 59,545, 95% CI =3,467-1022,665; p = 0,005). Conclusion The need for dialysis at the time of AAV diagnosis is a strong predictor for ESRD and relapse rate. It is also interesting to further study differences between patients needing dialysis at the time of diagnosis and those who don’t need it.

P0456LONG TERM PATIENT SURVIVAL AND RELAPSE RATE IN ANCA ASSOCIATED PATIENTS WITH RENAL INVOLVMENET - DATA FROM CROATIAN REFERRAL CENTER

Abstract Background and Aims The aim of the research was to evaluate patient and renal as well as relapse free survival in ANCA associated vasculitis (AAV) patients in our center. Despite the advances in understanding pathogenesis of AAVs and advances in treatment, the outcomes of AAV patient differ in various centers. Method This study included 106 consecutive AAV patients with renal involvement in the period from 2007-2017. We performed renal biopsy on patients using automatic 16 Gauge needle. Light, immunofluorescent and electronic microscopy were performed. All the patients were treated with cyclophosphamide and steroids in induction treatment with adjuvant PLEX and dialysis depending on renal function and lung manifestations. Primary outcomes were combined outcome progression to end-stage renal disease, defined as persistent (more than three months) need for renal replacement therapy or permanent reduction of EGFR to <15ml/minute (according to CKD EPI formula) and/or death (ESRDD), death (D) and ESRD alone, and disease relapse. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between phenotypes and finding significant predictors regarding outcomes. Out of 106 patients (55,6% female, median age 61; IQR 51-70) there were 66 (61,1%) microscopic poliangitiis (MPA), 20 (18,5%) granulomatosis with angitiis and 20 (18,5%) with renal limited vasculitis (RLV),There were 14 (13%) PR3-ANCA positive patients, 57 (52,8%) MPO ANCA positive, 5 (4,6%) PR3-ANCA+MPO-ANCA positive and 32 (29,6%) ANCA negative patients. Histologically (Berden classification) 43 (39,8%) patients had crescentic, 19 (17,6%) focal, 34 (31,5%) mixed and 12 (11,1%) sclerotic class. Follow up time ranged from 1 to 127 months. Median follow up time was 21 months (IQR = 7-44). Median time to diagnosis was 3 months (IQR 2,0-6,0). Results During follow up 21 (19,8%) patients died, 26 (24,5%) patients reached ESRD and 10 (9,4%) patients relapsed. There was no significant difference in outcomes between clinical, serological or histological phenotypes. In multivariant analysis independent predictors for death were age (HR = 1,059, 95% CI =1,001-1,120; p = 0,046), anemia (HR = 0,952, 95% CI =0,908-0,998; p = 0,040) and BVAS (HR = 1,093, 95% CI =1,030-1,159; p = 0,003), for ESRD. the need for acute dialysis (HR = 4,674, 95% CI =1,996-10,946; p = < 0,001), and interstitial fibrosis and tubular atrophy (IFTA) percentage over 50% (HR = 2,652, 95% CI =1,157-6,081; p = 0,021). and for relapse rate younger age (HR = 0,924, 95% CI = 0,870-0,981; p =0,010), lower serum creatinine levels (HR = 0,996, 95% CI = 0,992-1,000; p = 0,033), and the need for acute dialysis (HR = 59,545, 95% CI =3,467-1022,665; p = 0,005). Event free survival after 12, 24, 36 and 60 months was for death 83,9, 81,2, 79 and 74,7%, for ESRD 80,6, 77,9, 76,1 and 71% and for relapse 95,3, 88,4, 88,4 and 85%. Conclusion Timely diagnosis and treatment can ensure better outcomes in AAV patients. Though there is an overlap in predictive factors between different cohorts, there are still distinctive differences especially between cohorts from clinical trials and those from observational studies. Our study is among few to show significance of anemia as clinical predictor and IFTA percentage as pathohistological predictor.

P0124PREDICTIVE VALUE OF RENAL RISK SCORE AND CHRONICITY SCORE IN PREDICTING RENAL OUTCOME IN ANCA ASSOCIATED GLOMERULONEPHRITIS

Abstract Background and Aims Renal Risk Score (RRS) and Chronicity Score (CS) are both newly proposed tools to predict End stage renal disease (ESRD) which could be applicable in Antineutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (AGN) patients. Their predictive value has not been fully studied and compared. Method Patients with newly biopsy-proven AGN at Department of Nephrology, Ruijin Hospital were retrospectively studied. Patients were evaluated with RRS and CS for clinical factors, pathological lesions and outcome. Their predictive value of renal survival was also compared with 2010 histological classification. Results There were 252 AGN patients enrolled in current study, including 212 MPA, 12 GPA, 4 EGPA and 24 renal limited vasculitis (RLV). In current study, the median serum creatinine of patients at diagnosis was 245.5 μmol/L (IQR 128-487.5 μmol/L) and median eGFR was 20.3 ml/min (IQR 9-45.3 ml/min). Fifty (19.8%) patients required dialysis at disease onset. The median RRS score at diagnosis was 6 (IQR 0-9) and CS score was 4 (IQR 3-7). During up to 217 months of follow-up (mean 63.9 months), 71(28.2%) patients progressed to end stage renal disease (ESRD) and required renal replacement therapy. Significant differences were found regarding dialysis dependency within RRS and CS groups (p<0.001 and p<0.01 respectively). The C statistic of the predictive models was 0.828 (95% CI, 0.775-0.880) for developing ESRD required renal replacement therapy. The addition of RRS or CS scoring scheme to the model significantly improved discrimination. Compared with the 2010 histopathological classification, RRS and CS both showed adequate and similar discrimination, but significantly greater discrimination than 2010 histopathological classification. Conclusion Among AGN patients, RRS and CS achieved similar discrimination, but the discrimination of RRS was superior.