Wegener's Granulomatosis Research Articles

#1030 Addressing the unmet need of patient reported outcomes in ANCA associated vasculitis, in routine clinical practice

Abstract Background and Aims ANCA associated vasculitis (AAV) is associated with increased morbidity. Recent years has seen improvement in clinical outcomes yet little work has been done to better understand the patient's role within this condition. Patient reported outcome measures (PROMs) are increasingly standard in clinical research outcomes, as well as an overall indicator for good quality patient care. With the exception of Robson et al AAV-PRO [1], little research has been done to develop validated disease specific tools for patients living with AAV. We aim to develop a disease specific tool that can be used in clinical practice to aid patients and clinicians in understanding and track changes in health-related quality of life (HRQoL) over time. Method AAV patients from a single centre were invited to take part in focus groups conducted using a semi-structured topic guide. Participants were asked to discuss topics relating to four broad areas; 1) the effects of AAV on everyday life and living, 2) the effects of treatment on everyday life and living, 3) the role of patients in health management and the patient experience 4) a review of existing generic and disease specific PROM tools (SF-36 and AAV-PRO). Audio transcript of each focus group was transcribed verbatim and data was analysed using a combination of inductive and deductive framework analysis [2]. Results Twenty-eight patients with AAV were invited to participate, 19 attended one of three, 2.5 hour focus groups, 2 patients failed to attend, 4 declined and 3 were unavailable. The mean age of participants was 66.6 +9.4 years and there was a near equal male to female split (10:9). The median time from diagnosis as 7.4 years. Three participants had active or newly diagnosed AAV with BVAS scores of >10. Five participants had previously required dialysis with 1 receiving a renal transplant. All participants received glucocorticoid and immunosuppressive therapy (cyclophosphamide and or Rituximab), 15 (78.9%) were still receiving immunotherapy. Full analysis of the qualitative data is being undertaken. Preliminary findings outlined what was most important to participants when considering HRQoL. Areas acknowledged included; self-identity, social roles e.g. fulfilling caring responsibilities, fears of relapse and disease and treatment burden. Fifty-six deductive and inductive codes were identified which have been further categorised. Participants felt existing tools lacked consideration of some key issues. Scoring systems were considered to be negativity worded e.g. mild, moderate, severe, with the term ‘none’ being the only positive option. Participants reported that existing tools overlooked positive factors which impact HRQoL, such as symptom validation, close clinician monitoring and improvement with treatment. Limitations were noted when trying to address transient or inconsistent symptoms and difficulty separating vasculitis from other health conditions when answering questions. Participants expressed a preference for using a PROM as part of their clinical care and felt that completing it prior to clinic would be most helpful and facilitate discussions with healthcare professionals. The use of an electronic-PROM was widely supported and would support clinicians and patients to monitor changes over time. Conclusion The AAV-PRO represents a significant advancement over generic tools such as the SF-36, however, existing PROMs are not without limitations and are primarily used in research practices. Our study revealed that patients desire active participation in HRQoL discussions and further work to incorporate this into the clinic setting is needed. We are continuing to develop a PROM tool that can be used to assess patients HRQoL in relation to their AAV in the outpatient setting. We believe this will allow a deeper understanding of the disease burden and could support a comprehensive, patient-centred approach to decision-making, offering new insights and identifying the need for supportive care. On a broader scale, these insights can be utilized to compare treatments, shed light on inequalities and facilitate enhancements in services.

#1774 ANCA vasculitis with renal involvement: age as a prognostic factor

Abstract Background and Aims Older patients with antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) commonly experience renal impairment and poor prognosis. The European Vasculitis Study Group trials showed that approximately 16.7% and 22.5% of older patients with AAV suffered from end-stage renal disease (ESRD) in 5- and 10-year durations. The aim of this study was to analyze differences in course and outcome of patients with AAV with respect to age. Method This retrospective observational study included patients with diagnosis of AAV and biopsy proven renal involvement between 2000-2021. Patients were divided into two groups according to age: ≥65 or <65 years old. We recorded baseline characteristics and clinical data during follow-up. Response was defined as a BVAS reduction of at least 50% or BVAS of 0, while receiving prednisone dose higher than 4 mg; and remission as BVAS of 0 while receiving prednisone dose of 4 mg or less. Results We included 42 patients with AAV diagnosis, 47.6% of which were 65 years-old or older. Mean age of the older age group was 77 ± 8 years. No differences were found between older and younger patients at baseline (BVAS, FFS extra-renal symptoms, serum creatinine at diagnosis, hematuria), Patients > 65 years were significantly more likely to present p-ANCA positive MPA, as shown in Table 1. There was no difference in initial or maintenance immunosuppressive therapy between the two groups. No differences were found between older and younger patients with regard to treatment response. Although we found no statistical differences, older patients had worse renal outcomes. The older adult group had a higher mortality rate, p 0.01. The average time to death was 27 months for patients over 65 years and 34.5 in those who were younger (p 0.71). Conclusion No differences were found between older and younger patients with regard to treatment response. However, mortality was higher during follow-up in the group of older patients. Our results suggest that more attention should be paid to older patients with severe renal impairment.

#1475 Anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) in real world life

Abstract Background and Aims Anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) is a rare disease and the different treatment with plasma exchange are still controversial. We evaluate the AAV-GN outcomes of the last ten years in our centre. Method We retrospectively reviewed the clinical presentations and outcomes of AAV-GN patients in our centre between 2013-2022. We compared the presentation and prognosis according to the type of ANCA, serum creatinine (SCr) and the use of plasma exchange (PLEX). We included patients with AAV and kidney biopsy with at least 6 months of follow-up. Patients with positivity for both MPO and PR3, anti-GBM antibodies or did not meet inclusion criteria were excluded. Results Of 64 patients reviewed, 13 were excluded: 3 lack of follow-up, 3 absence of renal biopsy, 3 ANCA negative, and 4 concomitant anti-GBM antibodies. A total of 51 patients were included in the analysis (Table 1): 28 women (54.9%), age 66.75 ± 15.24 years, (64.7% over 65 years) and 44 (86.3%) with ANCA-MPO (+). Results comparing ANCA-MPO and PR3 in Table 1. The most frequent form of presentation was anaemia with haemoglobin 9.87 ± 2.04 mg/dL, acute kidney injury (AKI) AKIN III (39.2%), median SCr 2.78 (1.58-5.22) mg/dL, 41 (80.4%) with microhematuria, proteinuria 2.62 ± 2.7g/g, and 8 (15.7%) alveolar haemorrhage. 18 patients (25.3%) required hemodialysis, and 7 (13.5%) were transient (4 requiring <1 month). Rituximab was more used than cyclophosphamide (p < 0.001). Of the patients treated with plasma exchange (PLEX, n = 11), 6 (54.5%) had alveolar haemorrhage and/or 7 (63.6%) SCr>5.6 mg/dL, with no further infections or mortality at one year. Of the patients diagnosed with SCr>5.6 mg/dL, 9 (81.8%) were men (p = 0.008), 7 (63.6%) received PLEX (p < 0.001) and 6 (54.4%) died (p = 0.003). As expected, in the multivariate binary logistic regression SCr>5.6 at diagnosis was identified as independent risk factor for PLEX (p = 0.02, OR = 15.6 (95% CI 3.16-76.92). There were 13 deaths (25.5%), 6 in the first year after diagnosis. The most used maintenance treatment was MMF (52.9%), SCr and glomerular filtration rates at 2 years were 1.5 mg/dL and 45.36 mL/min/1.72 m² respectively. Conclusion The most common AAV-GN in our centre are ANCA-MPO+, and mainly affect people over 65 years of age, with rituximab being the most used treatment. ANCA-MPO+ patients have worse renal function at 18 months of follow-up. Mortality is higher in AAV-GN with serum creatinine greater than 5.6 mg/dL at diagnosis and in ANCA-MPO+. PLEX therapy is more used in cases of alveolar hemorrhage or severe renal involvement, without presenting an impact in our cohort in the incidence of infections or mortality at one year of follow-up.

#2889 Multiple renal tumors as an atypical clinical manifestation of granulomatosis with polyangiitis

Abstract Background and Aims Granulomatosis with polyangiitis (GPA) is a systemic small- vessel vasculitis associated with antineutrophilic cytoplasmic antibody (ANCA), in which kidney involvement often occurs. In some cases the course of vasculitis with kidney involvement is atypical, what complicates the diagnostic process and makes appropriate treatment difficult. Finding nodular masses in the kidneys always causes an oncological concern, while in the differential diagnosis a systemic vasculitis is rarely taken into account, what may lead to an unnecessary nephrectomy. Method We present a case of granulomatosis with polyangiitis (GPA) who presented with multiple tumors in the kidneys and adrenal gland. Results 29-year-old man experienced a sudden disease onset, at the age of 18 years, when due to peripheral oedema, nephrotic grade proteinuria (13.7 g/24 h), hematuria and presence of renal failure markers (serum creatinine 3.4 mg/dL), he was admitted to hospital. A suggestion of a rapidly progressive glomerulonephritis (RPGN) was put forward and a renal biopsy was performed (in the histopathological examination of the kidney, pauci-immune crescentic necrotizing glomerulonephritis was revealed). A treatment with plasmaphereses, high glucocorticosteroid doses and cyclophosphamide pulses was instituted. Haemodialysis therapy was also applied temporarily. ANCA and anti-glomerular basement membrane (GBM) antibodies were determined to give negative results. As a result of the remission-inducing treatment, an improvement of the renal function was obtained (serum creatinine 1.6-1.9 mg/dL). In spite of the remission-maintaining treatment with mycophenolate mofetil (MMF) and oral prednisone, after 10 years again a dramatic renal function impairment occurred, with a necessity of institution of a long-term haemodialysis therapy. Furthermore, on abdominal ultrasound examination multiple focal lesions were found in both kidneys, which rendered a kidney transplantation procedure in the patient impossible. In order to extend the diagnostic procedures, a magnetic resonance imaging (MRI) of the abdominal cavity without contrast agent administration was carried out (in both kidneys disseminated focal lesions were described: non-homogeneous, with moderately enhanced signal on T2-weighted images in the central part, without signs of water diffusion restriction; in the left kidney, of 23 x 22 mm and 19 x 15 mm dimensions; in the right kidney, of 30 x 32 mm, 26 x 22 mm and 22 x 18 mm dimensions. The picture of the lesions was unspecific and atypical. In the differential diagnosis granulomas could not have been ruled out, while disseminated proliferative lesions were less likely. Besides that, in both kidneys cysts of up to 7 mm diameters were present. In the lateral limb of the left adrenal gland a focal lesion was visible, of 23 x 14 mm dimensions, of a structure identical to that of the foci in both kidneys). On high-resolution computed tomography (HRCT) of the chest at the same time, small ground glass areas were found in the lungs. On positron emission tomography/computed tomography (PET/CT) no changes were visualised, suggesting presence of a metabolically active proliferative process. Tests for ANCA, antinuclear antibodies (ANA), anti- double-stranded DNA (dsDNA) antibodies, anti- GBM antibodies were again performed and gave negative results. He was diagnosed with granulomatosis with polyangiitis without ANCA and treated with corticosteroid and intravenous rituximab (4x 787 mg). Three months later, follow-up showed reduced mass lesions in the kidney and adrenal gland by MRI. Conclusion The case highlights the atypical clinical presentation of vasculitis and the significance of considering this possibility in differential diagnosis when confronting mass lesions present in the kidney.

#2276 Blood stream infections in patients with ANCA-associated vasculitis—a Danish nationwide study

Abstract Background and Aims Infection due to the immunosuppressive treatment, is among the most frequent causes of hospitalization and death in patients with ANCA-associated vasculitis (AAV). Information on prevailing causal microbial aetiologies is crucial for improving treatment and prevention of such events. Here we examined causal bacteriology, incidence, and risk of blood stream infections (BSIs) in incident and prevalent AAV patients, as compared to the general population. Method All data were retrieved from the Danish nationwide registries and the Danish Microbiology Database. Prevalent patients between 1998-2010 were all included at the same index date 1.1.2010; Incident patients diagnosed after 2010 were included with index being the day of diagnosis. Both groups were followed until first time BSI, death, or a maximum of 12 months. Background controls were matched 1:4 on age and sex. Cumulative incidence was assessed by the Aalen-Johansen estimator, and cox analyses adjusted for age, sex, kidney involvement, hypertension, diabetes, dialysis, and plasma exchange (PLEX), were used to model survival time. Results A total 19 (2.3%) BSIs were identified in 818 prevalent patients, and 55 (5.9%) BSIs in 939 incident patients (P < 0.001). As in the background control group, primary causal microbial agents among prevalent patients were E. coli (26.3%) and S. aureus (21.1%), with an overall Gram-negative predominance (58.8%). E. coli (17.5%) remained the most frequent microbial cause of BSIs in incident patients, however with a relatively higher frequency of gram-positive bacteria (50.9%) dominated by Coagulase-negative Staphylococci (12.3%), Enterococci (14%), and Streptococci (14%). Difference in bacteriology between prevalent and incident patients disappeared when patients on dialysis were excluded, whereas the difference in BSI frequency remained significant (p < 0.001). One-year HR of first-time BSI was significantly higher in patients with AAV as compared to controls (prevalent AAV: HR 3.17 [95% CI 1.63-6.18], p < 0.0001; Incident AAV; HR 8.64 [95% CI 4.88-15.31], p < 0.0001), with significant difference between incident and prevalent patients (HR 2.73 [95% CI 1.39-5.35], p = 0.003). Dialysis (HR 3.15 [95% CI 1.86-5.31], p < 0.0001) and PLEX (HR 1.87 [95% CI 1.05-3.33], p < 0.033) were solitary risk factors of BSI as well as higher age, hypertension, diabetes, and kidney disease (Figure). Risk of BSI remained significantly increased for both prevalent and incident patients as compared to matched background controls when patients on dialysis were excluded. Conclusion E. coli and S. aureus were predominant causal isolates in prevalent AAV patients and controls, and the gram-positive predominance seen with incident AAV was primarily caused by patients on dialysis. Risk of BSI was higher in incident AAV as compared to prevalent AAV, and the AAV diagnosis was associated with increased risk of BSI at all times, with highest risk initially after first diagnosis. Interventions requiring a central venous catheter were solitary risk factors of BSI.

#2837 Novel therapeutic for crescentic glomerulonephritis through targeting CLDN1 in parietal epithelial cells

Abstract Background and Aims Crescentic glomerulonephritis (CrGN) is the final mode of kidney injury common to several immune-mediated kidney diseases. CrGN is characterized by extensive glomerular parietal epithelial cells (PECs) proliferation forming crescents. The destructive crescent is then progressively replaced by fibrosis. Currents therapies for CrGN do not directly target the deleterious response of resident kidney cells. In a pathological context, claudin-1 (CLDN1), a transmembrane protein involved in epithelial tight junctions, can be exposed outside the tight junctions and mediate pro-fibrotic pathways and extracellular matrix (ECM) remodelling. Lixudebart (formerly ALE.F02) is a first-in-class monoclonal antibody that specifically targets and blocks exposed CLDN1 in injured epithelial cells. A phase II clinical trial is under way for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with rapidly progressive glomerulonephritis which induces kidney fibrosis (RENAL-F02, NCT06047171). CLDN1 is highly expressed by glomerular PECs. This study investigated the functional role of CLDN1 in CrGN and the potential benefit to target CLDN1 in CrGN. Method CLDN1 expression in renal tissues of CrGN patients was analyzed using kidney multicolor immunofluorescence staining and spatial transcriptomics. Correlation between CLDN1 expression and clinical endpoints (eGFR, proteinuria), disease biomarkers and crescent evolution were studied. A spatially resolved molecular roadmap from CLDN1+ crescentic glomeruli was conducted. Proof-of-concept studies using anti-CLDN1 mAb were performed in preclinical models of CrGN. Results In tissues (n = 150) of patients with AAV and IgAN, multicolor immunofluorescence revealed up-regulated CLDN1 expression by cellular and fibrocellular crescents. At the time of diagnostic kidney biopsy, glomerular CLDN-1 expression was correlated with podocyte loss (as measured with P57 staining) and fibronectin area. The extent of dual expression of CLDN1 and CD44 at the surface of active PECs was associated with poor renal outcome (eGFR < 30 ml/min) in AAV and IgAN patients with a median follow-up of 2.5 and 3.7 years respectively. Spatial transcriptomics analysis highlighted the association between CLDN1+ crescentic glomeruli and ECM genes. Treatment with anti-CLDN1 mAb reduced albuminuria, improved kidney function and decreased fibrosis biomarkers in nephrotoxic serum-induced CrGN in mice. Conclusion Our results suggest a functional role of CLDN1 in the pathogenesis of CrGN, providing preclinical proof-of-concept for anti-CLDN1 antibodies as a novel therapeutic approach in patients with CrGN.

#2256 Safety and effectiveness of avacopan beyond 52 weeks: experience to date in the Early Access Program (EAP)

Abstract Background and Aims ANCA-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), is characterized by a high burden of organ damage, as well as increased mortality [1]. Both the disease itself and the immunosuppression required for its management contribute significantly to poor prognosis [2]. Avacopan is a first-in-class C5aR1 antagonist that demonstrated efficacy and safety over 52 weeks in patients with GPA or MPA, and was associated with a significantly lower requirement of glucocorticoids for disease management [3]. Significant data on long-term avacopan use in the context of real-life settings are sparse. Here, we describe experience with avacopan in 59 patients with GPA or MPA treated beyond 52 weeks within an ongoing Early Access Program (EAP). Method Patients with newly diagnosed or relapsing severe, active GPA or MPA were treated in the EAP. Safety data, including lack of effect and other events (i.e., relapse or worsening of disease) in these patients were recorded in a CSL Vifor safety database from Feb 2019 – Dec 2023. We performed analysis of these data for patients treated beyond 52 weeks. Results 237 patients received ≥ 1 dose of avacopan with a median overall treatment duration of 7 months (range 1-45) at the time of this analysis. 43 of 237 patients had at least one adverse event (AE) reported (18.1%) with a median of 2 (range 1-11) AEs per patient; 19/237 (8.0%) patients experienced a serious AE (SAE). Most of the reported AEs belonged to the System Organ Classes (SOC) of infections and infestations, and gastrointestinal disorders, with COVID-19 being the most frequently-reported event. At the time of this analysis, 59 patients continued treatment beyond 52 weeks, with a median overall duration of treatment of 16 months (range 13-45). Within this group, 12 of 59 patients experienced at least one AE (20.3%) with a total of 46 AEs. 9/ 12 patients reported AEs during the first 52 weeks treatment, while in 3 patients the date of AE occurrence was not available (Table 1). The results in these 59 patients are summarized below. 6 patients experienced at least one SAE (7 SAEs in total). As in the overall EAP population, most of the reported AEs belonged to the SOC of gastrointestinal disorders, followed by infections and infestations, with COVID-19 being the most common AE occurring in 3 patients. 18 AEs were assessed as related to avacopan, with 3 events in 2 patients being classified as serious (deep vein thrombosis [DVT] in one patient, lower urinary tract symptoms and JC polyomavirus test positive in the second). The patient experiencing DVT temporary discontinued avacopan. In the patient who developed lower urinary tract symptoms with active replication of JC virus (1.728.405 copies/mL), avacopan was permanently withdrawn. According to the reporter, the concomitant use of prednisone, rituximab and denosumab could have contributed to these events. Three patients experienced events implying worsening of underlying disease. These events occurred within the first 52 weeks of treatment. The first patient experienced a vasculitis flare 6 months following avacopan initiation that coincided with an unintended dose reduction to 20 mg BID due to a product supply issue. The second patient experienced a worsening of known GPA related mononeuritis multiplex, possibly induced by concomitant treatment with isoniazid and a likely result of pharmacological interaction between rifampicin and avacopan. The third patient experienced an increase of creatinine, proteinuria and microhematuria in the context of avacopan withdrawal due to other events. Conclusion These results confirm that avacopan has a manageable safety profile with the potential to be effective beyond 52 weeks in sustaining disease control. Limitations of this analysis include potential underreporting, incomplete data and no control group.

#933 Serum and kidney complement and severity of ANCA associated vasculitis in the kidney

Abstract Background and Aims Kidney involvement in ANCA associated vasculitis (AAV) is commonly described as pauci-immune based on histological characteristics. However, we now know that the complement system is activated and contributes to the pathogenesis of AAV – with Avacopan (C5a inhibitor) demonstrating superior efficacy in maintenance of remission over Prednisolone in the ADVOCATE trial. Our aim was to evaluate if there is an association between kidney disease severity and the presence of serum and histological complement activation markers. Method Retrospective cohort study of 59 patients with AAV diagnosed between November 2015 and May 2019. Complement activation markers were serum complements (C3 and C4) levels and presence of complement (C3, C1q and C4) in glomerular capillary walls in immunofluorescence with intensity of 2+ and 3+. Kidney disease severity markers were peak serum creatinine value at presentation, anti-MPO or anti-PR3 levels, and number and proportion of glomeruli with crescents on kidney biopsy. Associations were evaluated using Spearman correlation or Mann Whitney U test as appropriate Results Among 59 patients with biopsy-proven AAV in the kidney, the median (25th percentile, 75th percentile) age was 68.8 (60.7, 73.4) years, serum creatinine was 263 (156, 560) µmol/L, and anti-MPO and anti-PR3 levels were 100.0 (81.5, 199.2) and 128.8 (22.9, 200) in 41 and 7 patients, respectively. respectively. The number and proportion of glomeruli with crescents were 6 (3, 12) and 33.3% (12.0%, 42.6%), respectively. Serum C3 and C4 were performed in 41 patients and the median levels were 1.00 (0.83, 1.14) and 0.24 (0.18, 0.31), respectively. Serum C3 level did not correlate with serum creatinine, anti-MPO or anti-PR3 titers, and number and proportion of glomeruli with crescents. Serum C4 level was negatively correlated with anti-MPO titer (34 patients; r = −0.393, p = 0.02) but did not correlate with serum creatinine or number or proportion of crescents. Complement in the glomerular capillary wall was present in 8 patients (13.6%): C3, C1q and C4 were present in 8, 3 and 1 patients, respectively. Serum creatinine [median 299 (IQR 133, 998) µmol/L versus 261 (156, 359) µmol/L, p = 0.39], anti-MPO titer [100 (88.3, 200) IU/ml versus 100 (79.4, 198) IU/ml, p = 0.74], number of crescents [14 (4, 21) versus 5 (3, 12), p = 0.90] and proportion of crescents [38.9% (12.5%, 42.3%) versus 31.3% (11.1%, 44.3%), p = 0.59] were not different in those with and without complement in the kidney biopsy. Conclusion The presence of complement activation markers was not associated with kidney disease severity in AAV. However, the detection of clinically significant associations may have been limited by our cohort size.

#1770 Clinical characteristics and outcomes in patients with ANCA-associated vasculitis (AAV) and kidney involvement—a Swedish single-center cohort

Abstract Background and Aims Poor patient outcomes in ANCA-associated vasculitis (AAV) with kidney involvement is attributed to multiple factors such as delay in diagnosis, inadequate efficacy of treatments and long-term complications due to the disease as well as the toxic effects of immunosuppressive therapy. The aim of the present study was to evaluate the clinical characteristics of a Swedish cohort of patients with AAV (granulomatosis with polyangiitis; GPA and microscopic polyangiitis; MPA) and kidney involvement to study causes of death and predictors of all-cause mortality. Method This retrospective single-centre cohort study included 93 patients from the Uppsala region in mid-Sweden, diagnosed with AAV and kidney involvement between 1993 and 2023. Clinical and laboratory variables were obtained from review of electronic medical records as well as patient follow-up visits. Differences between groups were assessed using independent t-test and Chi-square test. Multivariable logistic regression analyses were performed to evaluate the influence of risk factors of interest on all-cause mortality. Results 93 patients, 71 (76%) were clinically diagnosed with MPA, and 22 (24%) with GPA. The median age at diagnosis was 66.5 ± 13 years. eGFR at diagnosis was 29 ± 23.5 ml/min/1.73 m2 and 15% of patients were dialysis-dependent AAV at diagnosis. Patients with MPA and GPA received comparable induction therapy except for PLEX which was significantly more frequent in patients with GPA (52% vs 26% respectively, p = 0.041). 56 (60%) of patients died during follow up and survival time was 7.1 ± 6.9 years. Baseline clinical and biochemical characteristics are shown in Table 1. A multivariate logistic regression showed that older age at diagnosis (OR 95% CI 1.012-1.110; p = 0.013) and being dialysis-dependent at diagnosis (OR 95% CI 1.343-16.079; p = 0.015) significantly predicted all-cause mortality (Table 2). Causes of death are presented in Fig. 1. Infections was the most common cause of death (30%). Conclusion Long-term prognosis and patient survival were significantly associated with age and dialysis-dependency at diagnosis in this cohort of patients diagnosed with AAV and kidney involvement. Infections was the most common cause of death.

#1700 Clinical presentation and prognosis in ANCA-associated vasculitis with occupational exposure to silica: a monocentric retrospective study

Abstract Background and Aims Exposure to silica is associated with an increased risk of autoimmune diseases, including ANCA-associated vasculitis (AAV) [1–3]. It remains unclear whether silica exposure modifies clinical presentation of AAV, and it is not known whether it affects prognosis. The aim of this work is to address these questions. Method This is a retrospective, monocentric observational study comparing clinical and prognostic features between two groups of patients with ANCA-positive AAV: cases with a well-documented history of occupational exposure to silica (confirmed by industrial hygienists) and controls with no exposure. Each case was matched to 2 controls based on time of diagnosis (± 1 year relative to the case). Clinical features were compared across the two groups using Student's t test or chi-squared test, as appropriate. Clinical outcomes were compared across groups with the log-rank test and Cox proportional hazards regression. Results We identified 25 patients with AAV and a clear-cut history of occupational exposure to silica and 50 controls with no exposure, diagnosed between 2000 and 2023. Compared to controls, patients exposed to silica were more frequently males and smokers (Table). Average age at presentation was 66 ± 14 years and most patients had microscopic polyangiitis and MPO-ANCAs, with no significant differences according to silica exposure (Table). Patterns of organ involvement were also comparable across the two groups (Table). Renal vasculitis was present in almost all patients, probably reflecting a referral bias. Severity of renal impairment at diagnosis (Table) and evolution to end stage renal disease (Figure) were similar between exposed and unexposed individuals. There was a trend for lower survival in patients with exposure to silica (median survival from AAV diagnosis: 172 months in cases and 111 months in controls, log-rank test p = 0.065, Figure). In multivariate Cox regression, the risk of death was independently associated with age at diagnosis (HR 1.09 per year, 95% CI 1.04-1.14, p < 0.001) and not with silica exposure (HR 0.96, 95% CI 0.39-2.41, p = 0.936) or smoking history (HR 2.06, 95% CI 0.80-5.33, p = 0.135). Conclusion Patients with AAV and exposure to silica were more frequently males and smokers, likely reflecting socio-economic factors. We did not identify otherwise distinct clinical features in exposed patients, similarly to other Authors such as Hogan et al [2]. Exposure to silica did not seem to significantly affect renal prognosis or survival either, despite a trend in univariate analysis for higher mortality in individuals with silica exposure. The limited sample size and lack of quantification of silica exposure must be acknowledged and may have reduced statistical power.

#1646 Impact of sex in clinical presentation and outcomes of patients with ANCA-associated vasculitis with severe kidney disease

Abstract Background and Aims Biological sex has been associated to a more rapid rate of chronic kidney disease progression (ie, speed of kidney function loss) in male than female [1]. Testosterone can increase oxidative stress, activate the renin angiotensin system, and aggravate renal fibrosis, whereas estrogens inhibit these pathological processes in the diseased kidney [2]. Several factors such as lower disease awareness and surveillance rates as well as disparities in health-care access result in late initiation or lack of kidney replacement therapy among females [3-5]. The impact of sex in the clinical presentation and outcomes of patients with anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) has not been studied, particularly in patients with severe kidney involvement at presentation (eGFR<15 mL/min/1.73 m2). Method A retrospective cohort study on MPO- or PR3-ANCA positive patients with AAV (MPA or GPA) and eGFR<15 ml/min/1.73 m2 or ESKD at presentation. Clinical presentation and outcomes (renal recovery, dialysis at presentation, and ESKD) were analyzed according with sex. Results We analyzed 166 patients with biopsy proven active AAV-GN and eGFR <15 mL/min/1.73 m2 at the time of diagnosis (Fig. 1): 78 (47%) were females and 88 (53%) were males. Arterial hypertension was more frequently present in males (85.2% vs. 70.5%, p = 0.022). Median serum creatinine (SCr) was higher in males when compared with females (5.2 [IQR 4.2-7.4] vs. 3.6 [IQR 2.8-5.1] mg/dL, p < 0.001) but there were no differences in eGFR at presentation. When analyzing only the 71 (24 females and 47 males) patients that started dialysis within 4 weeks, infections at 12 months were more common in females (75.0% vs. 36.2%, p = 0.017). The rate of dialysis initiation or progression to ESKD was not different between males (15, 62.5%) versus females (29, 61.7%) being on dialysis at 12 months. By multivariable logistic regression, factors related with dialysis initiation within 4 weeks in our cohort were SCr (OR1.478, [95% CI 1.231-1.776], p < 0.001), alveolar hemorrhage (OR 2.726, [95% CI 1.099-6.763], p = 0.031) and PR3-ANCA (OR3.155, [95% CI 1.485-6.702], p = 0.003) adjusted to sex). Patients who remained on dialysis at 12 months more often had higher SCr at diagnosis (IRR 1.098 [95% CI, 1.026–1.175], p = 0.007), severe chronicity changes on kidney biopsies (IRR 2.469 [95% CI,1.205–5.061], p = 0.014), higher chronicity score (IRR 1.178 [95%CI, 1.062-1.308], p = 0.002) and lower hemoglobin (IRR 0.824 [95%CI, 0.683-0.994], p = 0.043). Minimal chronicity changes were protective for the achievement of this endpoint (IRR 0.228 [95% CI, 0.070-0.741], p = 0.014). Multivariable Cox regression showed that patients with higher SCr at diagnosis and moderate/severe chronicity changes on biopsy were at higher risk to evolve to ESKD at 12 months compared to patients with lower chronicity grades, even when adjusted to sex. Conclusion In our cohort, male patients presented with higher SCr, and dialysis was started within 4 weeks more frequently. However, this did not result in different outcomes in terms of kidney recovery, overall dialysis rates, and progression to ESKD in patients with AAV-GN and eGFR<15 mL/min/1.73 m2 between groups.

#2201 Assessment of long-term cardiovascular comorbidities in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Abstract Background and Aims ANCA associated vasculitis (AAV) is closely correlated to elevated cardiovascular disease (CVD) rates, positioning it a one of the leading causes of death among these patients. The impact of AAV on the risk of CVD has not been described in large prospective cohorts with a long-term follow up. The aim of our study was to evaluate the occurrence of cardiovascular events, encompassing major adverse cardiovascular events (MACE), to delineate associated risk factors, and to draw comparisons with other cohorts of patients diagnosed with CKD. Method We included 848 patients with a diagnosis of AAV who participated in 7 EUVAS RCTs (NORAM, CYCAZAREM, CYCLOPS, MEPEX, IMPROVE, RITUXVAS, and MYCYC), recruited from 74 centers in 17 European countries. The three-point MACE outcome was defined as acute myocardial infarction (AMI), stroke, or death from cardiovascular event. We used multivariate logistic regression analysis to assess the risk factors of MACE. Patients from our cohort were compared to the patients from the Chronic Renal Insufficiency Cohort (CRIC), which is a multicenter, prospective observational cohort study of participants with CKD. Results During the median follow up of 8 years (range 0-24.5, IQR: 2.9-13.6), 100 (11.8%) patients developed diabetes, 98 (13.4%) coronary heart disease (CHD), 90 (12.1%) hypertension, 70 (9.6%) deep vein thrombosis (DVT), 43 patients (5.9%) had a stroke and 28 (3.8%) an AMI. The number of MACE during FU was 144 (17%). MACE was more frequent among patients older than 65 years (n = 62 (43.1%); p-value: 0.013). CVD was the primary cause of death in 43 patients (14%). During the first 5 years after randomization, there was a significant increase in the number of cardiovascular events compared to the period 6 years- end of follow up (CHD: n = 55 vs n = 23, p ≤ 0.001; DVT: n = 55 vs n = 29; p < 0.001; stroke: n = 35 vs n = 24, p-value < 0.001). The prognostic factors for MACE in our cohort were hemodialysis dependency during RCT, age, male sex, previous history of CHD and stroke, and occurrence of diabetes during follow up. Within the subset of patients who underwent kidney biopsy, those in the crescentic class (n = 16) followed by the mixed class (n = 15) exhibited a significant higher incidence of MACE (p = 0.02). When compared to the cohort of patients with CKD from the CRIC study, the risk for CHD was higher (13.4% (95% CI: 11.16-16.11) vs 5.4% (95% CI 4.5-6.5); respectively; RR: 2.49 (95% CI 1.91-3.24); p-value<0.01). Additionally, there was a higher risk for stroke (5.6% (95% CI 4.2-7.4) vs 2.8% (95% CI 2.2- 3.7); RR 1.97 (95% CI: 1.33- 2.91) p-value: 0.0006). Conclusion Patients with AAV had an increased risk of stroke and CHD compared to patients with CKD from other etiologies. During the first years after diagnosis, there is an increased risk for CVD occurrence. The prognostic factors for MACE in our cohort were hemodialysis dependency, age, male sex, previous story of CHD and stroke, and diabetes during follow up. Patients with AAV should be considered at high cardiovascular risk; therefore, the therapeutic approach should include the management of traditional cardiovascular risk factors and lifestyle modification. Efforts should be made to meet strict therapeutic targets and to implement early CVD detection programs.

#1154 Type I interferon pathway is upregulated in microscopic polyangiitis (vs granulomatosis with polyangiitis)

Abstract Background and Aims The two main types of ANCA-associated vasculitis (AAV), microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), share common characteristics but also differ on many aspects (epidemiological, genetic, clinical, outcomes). These differences did not justify, to date, different patient management. To identify more specific targetable pathways, we characterized the kidney transcriptome of MPA vs. GPA patients with AAV-glomerulonephritis (AAV-GN). Method This retrospective study included adult patients with AAV-GN from the French Maine-Anjou Registry. Immune gene transcript analysis was performed on RNA extracted from 97 kidney biopsies using NanoString technology. Significant transcripts were examined to identify immune pathways of interest. We then used a publicly available dataset to explore these identified pathways (qPCR / ELISA). Results We compared kidney biopsies from GPA (n = 33) and MPA (n = 64) patients. There was no difference in eGFR between both groups at diagnosis. Of the 750 evaluated immune transcripts, 8 genes were found differentially expressed between MPA and GPA patients, all being upregulated in MPA (log2FC > 1, q-value < 0.05) (Fig. 1A). Seven (out of 8) genes belonged to the type I interferon (IFN-I) signaling pathway. A personal analysis of unpublished, publicly available, data1 identified a significantly more pronounced IFN-I signature in the peripheral blood mononuclear cells of patients with MPO-AAV when compared to those with PR3-AAV (Fig. 1B). Serum levels or CXCL10, a cytokine that mediates immune responses through the recruitment and activation of numerous immune cells under the regulation of IFN-I, were found higher in MPO-AAV patients (Fig. 1C). Conclusion We identified a type I interferon signature, both in kidneys and in blood, in patients with MPA (or MPO-AAV) in comparison to GPA (or PR3-AAV). This is in line with previous lines of evidence brough by Kessenbrock et al. and Kessler et al. suggesting a role for IFN-I in AAV and especially in MPO-AAV. This signature may help gain a deeper understanding of the AAV-GN pathogenesis and provide insights for developing new therapeutic options.

#1800 Cascade filtration in severe pulmonary-kidney syndrome: an one-center experience

Abstract Background and Aims In some forms of rapidly progressive glomerulonephritis (RPGN), the effect of plasma exchange (PE) is not well understood. Cascade filtration (CF) differs from standard PE in that it uses a double filter system, where the first filter is used to separate plasma from whole blood and the second filter is used to filter high-molecular weight substances. In this study, we investigated the efficacy and safety of CF in patients with ANCA-associated vasculitis (AAV) and Goodpasture's syndrome (GPS). Method During one year we included 18 patients with RPGN whose received CF in the study. The eligibility criteria was eGFR ≤15 ml/min/1.73 m2 and/or diffuse alveolar hemorrhage (DAH), presence of antineutrophilic antibodies or anti-GBM-antibodies. CF was performed on a Plasauto Sigma using a Plasmaflo OP-05W plasma separator and a Cascadeflo EC-30W separator with a fresh frozen plasma or 25% albumin solution. All patients received immunosuppressive therapy with steroids and cyclophosphamide, one patient with AAV received rituximab due to anemia and thromobocytopenia. All data were obtained from one hospitalization with the median of 43 days. Results Eight patients with AAV and three patients with GPS met the eligibility criteria. The median age of the patients in the AAV group was 59.8 (48; 66) years, with a female to male ratio of 1:1. All patients had evidence of systemic disease: seven patients had lung damage, including DAH, two patients had arthralgia, one had purpura and one had severe sinonasal involvement. The median creatinine level was 588 µmol/l (382; 1352), dialysis was initiated in 6 patients, and the median Birmingham Vasculitis Activity Score (BVAS) was 17 (15; 20). After three procedures of CF, all patients showed positive changes on CT scan, and dialysis was stopped in three patients. The immunological response to CF was observed quite rapidly in seven patients, with decreasing ANCA titer after three exchanges and decreasing antibody levels after six exchanges in one patient. There was a significant decrease in inflammatory markers, median C-reactive protein at baseline 179 (147; 226) decreased to 23 (2.8; 30.9) mg/l (p = 0.041). The CF was well tolerated with no significant adverse events. One patient receiving rituximab died after 4 months due to a severe COVID 19 infection. Three patients with GPS, one male 23 years old and two females 56 and 60 years old, also received CF. Creatinine concentrations at baseline were 1285, 1299 and 661 µmol/l, BVAS scores were 18, 20 and 15, respectively. After three procedures of CF, there was an immunological response: decrease in antibody levels from 121 U/ml to 15 U/ml, from 88.2 to 18.4 U/ml, from > 200.0 to 85.4 U/ml, CRP from 252 to 0.7 mg/l, from 120 to 5 mg/l, from 81.9 to 12.58 mg/l. There were no deaths and all three patients remained on dialysis. Conclusion CF was an effective and well tolerated method of treating severe AAV and GPS in addition to immunosuppressive treatment. Possibly due to the different filtration principle and the absence of donor plasma, we did not observe any infection-related adverse events and a lower number of procedures of CF was required compared to standard plasma exchanges. Further larger studies are needed to evaluate the benefits and safety of CF in combination with immunosuppressive treatment in RPGN patients.

#1828 Venous thromboembolic events in ANCA associated vasculitis patients—data from Croatian referral center

Abstract Background and Aims Our aim was to investigate the prevalence of venous thromboembolic events (VTE) in a cohort of patients with ANCA-associated vasculitis (AAV) and define factors associated with the frequency of VTE considering there is data on high incidence of VTE in AAV patients. In these cohorts VTE occurred mostly early in the course of disease. Method This study included 114 consecutive AAV patients with biopsy proven renal involvement in the period from 2007-2017. Patients were classified according to clinical: granulomatosis with poliangitis (GPA), microscopic polingitis (MPA) and eosinophilic granulomatosis with poliangitis (EGPA) and serological phenotype: MPO-ANCA positive, PR3-ANCA positive, MPO- and PR3-ANCA positive and ANCA-negative. Ordinal variables were analysed using logistical regression test. Statistical analysis was done in MedCalc Statistical Software version 18.11.6 (MedCalc Software Bvba, Ostend, Belgium). Results In the cohort there were 64 (56%) females, mean age was 58 (IQR 16-84) with mean follow up time 46.9 months (IQR 1-127). Clinically there were 84 (73%) patients with MPA, 26 (22%) with GPA and 4 (5%) with EGPA. Serologically there were 20% PR3-ANCA, 54% MPO-ANCA, 8% MPO- and PR-3 ANCA positive patients and 18% ANCA-negative patients. Mean serum creatinine levels (SCr) was 380.9 μmol/l (IQR 65-1402). Mean BVAS (Brimingham vasculitis score) at the time of diagnosis of AAV was 17 (IQR 5-50) and at the time of VTE 0, 9 (0-22). Mean body weight was 71kg (IQR 48-110) and mean CRP was 84 mg/ml (IQR 0, 3-256). During the follow up 7 (6.14%) of the patients had VTE, with 4 having VTE in first month after the diagnosis and other two at month 14 and 19. Logistic regression showed the connection of weight (P = 0.0052) and CRP (0.0138) with VTE with odds ratio of 1,0829 for CRP (1.003-1.027) and 1.0150 for weight (1.0284-1.1736) respectively. There was no statistical significance for clinical or serological phenotype being associated with VTE nor for other clinical or laboratory parameters. Conclusion In our cohort patients with AAV were at risk of VTE, particularly within the first year following onset of disease. In this cohort the frequency of VTE did not depend of clinical or serological AAV phenotype, age or gender. Only CRP and body weight were associated significantly with VTE occurrence. Despite VTE rates in AAV patients, routine anticoagulation is not recommended in AAV patients, given the potential risk of bleeding complications. Prospective studies are needed to assess VTE risk stratification in AAV patients and to evaluate the both benefits and potential risks ratio of prophylactic anticoagulation in AAV patients.

#2727 Acute kidney in patients with ANCA associated vasculitis

Abstract Background and Aims Renal involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is considered an emergency situation. Early diagnosis and treatment significantly improve prognosis. The aim of this study was to investigate the characteristics of acute kidney injury (AKI) in ANCA-associated vasculitis and assess its developmental aspects. Method Our study, conducted in the Internal Medicine Department A of Charles Nicole Hospital over a four-year period (January 2018-August 2022), was retrospective and descriptive. The diagnosis of ANCA vasculitis was made based on the ACR 1990 and/or EULAR 2012 criteria. The severity of AKI was categorized according to the KDIGO AKI classification. Results Seventeen patients were included, with a mean age of 51 ± 17.42 years and a sex ratio of 0.42. The primary clinical presentation of AKI was rapidly progressive glomerulonephritis (n=11), followed by acute nephritic syndrome (n=4). Pneumo-renal syndrome was observed in 4 patients. Proteinuria and hematuria were present in all 17 patients, with 4 being oligoanuric on dipstick. The mean creatinine level was 584 μmol/L, ranging from 125 to 1151 μmol/L. Thirteen patients had KDIGO stage 3 AKI on admission. The predominant histological lesion was extracapillary crescentic glomerulonephritis, based on the Berden classification (n=6). Hemodialysis was initiated immediately in 12 cases, and plasma exchange was performed in 10 cases. The average follow-up time was 24 months, ranging from 3 months to 4 years. Evolution was marked by partial remission in 7 cases, with a mean creatinine of 173 μmol/L. Progression to end-stage renal disease (ESRD) occurred in 10 cases. Relapses, presenting as pneumo-renal syndrome, were observed in 4 patients. Seven patients succumbed, with vasculitis being the cause of death in 3 cases. In univariate analysis, age >70 years was associated with progression to ESRD (p=0.03). No factor studied emerged as a prognostic factor for overall survival. Conclusion The presence and severity of AKI in ANCA-associated vasculitis are linked to a poorer prognosis, affecting both patient and renal survival.

#211 Low albumin levels are associated with intrarenal complement C4d deposits in critically ill patients with ANCA-associated renal vasculitides

Abstract Background and Aims Despite serum albumin levels being predictive for clinical outcome in ANCA-associated renal vasculitis, implications providing a direct link between low serum albumin levels and intrarenal lesions remain elusive. Therefore, we here aimed to systematically assess the clinical relevance of low albumin levels and scrutinize clinicopathological correlations to expand our current knowledge. Method We here retrospectively enrolled biopsy-proven cases of ANCA-associated renal vasculitis between 2015 till 2020 in a single-center observational study. Survival-curve analyses on long-term renal survival and short-term clinical recovery were performed. Correlative analyses between serum albumin levels, laboratory parameters, proteinuria levels, and histopathological lesions including tubulointerstitial immune cell infiltrates, lesions analogous to the Banff score and intrarenal complement deposition of C3c and C4d were performed. Results We here show that hypoalbuminemia below the median of 2.4 g/dL impairs long-term renal survival especially in MPO-positive ANCA-associated renal vasculitis (p = 0.006, HR: 5.0, 95% CI: 1.2-21.5), while short-term clinical recovery particularly in critically ill patients is negatively affected by low serum albumin levels (p = 0.0082, HR: 3.6, 95% CI: 1.1-11.7). Low albumin levels are associated with the urinary marker of tubular damage in the total cohort (β = −0.5, p = 0.01), PR3-ANCA (β = −0.5, p = 0.04) and MPO-ANCA (p = 0.002, β = −0.8), but not in critically ill patients (β = −0.5, p = 0.07) implying hypoalbuminemia to occur by extrarenal causation in the state of critical illness. We identified plasmacytic infiltrates to correlate with low albumin levels in the total cohort (β = −0.6, p = 0.004) and in the subgroup of critically ill patients (β = −0.7, p = 0.005). Banff-scored interstitial inflammation (i) was further observed to inversely correlate with albumin levels (β = −0.7, p = 0.02). Intrarenal C4d deposition showed a significant correlation with low serum albumin levels in the glomerular tuft (β = −0.4, p = 0.04) and in interstitial arteries (β = −0.7, p = 0.01). Conclusion In conclusion, long-term renal outcome is significantly affected by low serum albumin levels especially in the setting of MPO-ANCA seropositivity. By contrast, short-term recovery was predicted by low albumin levels in critically ill patients with ANCA-associated renal vasculitis. We here provide evidence that low levels of serum albumin might directly affect tubulointerstitial inflammation as reflected by plasmacytic immune-cell infiltration, and intrarenal C4d complement deposition in ANCA-associated renal vasculitis.

#386 Avacopan versus prednisone taper in newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis in the ADVOCATE trial

Abstract Background and Aims In granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), two types of antineutrophil cytoplasmic autoantibody-associated vasculitis, relapses are common, with 14–44% of patients experiencing a relapse at 18–36 months, depending on patient characteristics, duration of follow-up, and maintenance treatment [1]. In the phase 3 ADVOCATE trial, 69% of patients were newly diagnosed and 31% had relapsing GPA/MPA [2]. This post hoc subgroup analysis of ADVOCATE evaluates the safety and efficacy of avacopan compared with a prednisone taper in patients with newly diagnosed or relapsing GPA/MPA. Method ADVOCATE, a randomised, double-blind, double-dummy, active-controlled clinical trial, assigned eligible patients 1:1 to receive avacopan or a prednisone taper on a background of either cyclophosphamide (followed by azathioprine or mycophenolate mofetil) or rituximab. Data from patients with newly diagnosed (N = 229) or relapsing (N = 101) GPA/MPA were analysed. Key outcomes were the percentage of patients achieving remission at week 26 and sustained remission at week 52. Other outcomes included relapse rate, change in estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), glucocorticoid dose (prednisone-equivalent), Glucocorticoid Toxicity Index (GTI), health-related quality of life (HRQoL), and safety. Results Baseline characteristics were comparable between the avacopan and prednisone taper arms within each disease status group (Table 1). Efficacy outcomes are reported in Table 2. At week 26, similar proportions of patients with newly diagnosed GPA/MPA achieved remission in the avacopan and prednisone taper arms (66.1% vs 66.7%; difference [95% confidence interval (CI)]: −0.6% [−12.8, 11.7]). In the relapsed group, a numerically higher proportion of patients receiving avacopan than those receiving a prednisone taper achieved remission at week 26 (86.3% vs 78.0%; difference [95% CI]: 8.3% [−6.6, 23.1]). Compared with the prednisone taper arm, the proportion of patients who achieved sustained remission at week 52 with avacopan was similar in newly diagnosed GPA/MPA (60.9% vs 57.9%; difference [95% CI]: 3.0% [−9.7, 15.7]) and higher in relapsed GPA/MPA (76.5% vs 48.0%; difference [95% CI]: 28.5% [10.4, 46.6]). The relapse rate over 52 weeks after remission at any time was lower with avacopan than with a prednisone taper in both newly diagnosed (8.2% vs 18.2%) and relapsed (14.6% vs 27.7%) GPA/MPA. There was a larger improvement in eGFR over 52 weeks (newly diagnosed: 8.1 vs 5.3; relapsed: 5.0 vs 0.7) and earlier reduction in UACR at 4 weeks (newly diagnosed: −42% vs −1%; relapsed: −32% vs 3%) in the avacopan arm than in the prednisone taper arm. The total all-source median glucocorticoid dose was 625 mg in the avacopan arm compared with 3048 mg in the prednisone taper arm for newly diagnosed GPA/MPA, and 500 mg in the avacopan arm compared with 3139 mg in the prednisone taper arm for relapsed GPA/MPA. At week 26, the GTI cumulative worsening and aggregate improvement scores were lower (more favourable) with avacopan than with a prednisone taper in both arms. The change from baseline in both analysed HRQoL scales was numerically higher with avacopan than with a prednisone taper at week 52 in both groups (Table 2). Fewer adverse events per patient were reported with avacopan vs a prednisone taper in both disease status groups (Table 1). Conclusion In this post hoc subgroup analysis of the ADVOCATE trial, efficacy and safety outcomes in patients with newly diagnosed or relapsed GPA/MPA favoured avacopan compared with a prednisone taper, supporting the use of avacopan in these patient types. The observed clinical efficacy of avacopan especially in patients with relapsing GPA/MPA provides valuable insights into the treatment of this difficult-to-treat subgroup.

#1356 Kidney phenotype in interstitial lung disease associated with ANCA-vasculitis: European Multicentre Study

Abstract Background and Aims Interstitial lung disease (ILD) in ANCA-associated vasculitis (AAV) has the appearance of a progressive fibrotic disease on imaging and primarily affects the interstitial lung compartment and is usually associated with MPO-ANCA. Whether patients with AAV-ILD display a similar fibrotic pattern in their kidneys is unclear. Method A European multicentre retrospective study included patients with AAV-ILD. The diagnosis of ILD was confirmed by a CT chest pattern of usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), organising pneumonia or chronic hypersensitivity pneumonia. We aimed to determine if kidney involvement in AAV-ILD exhibited a more fibrotic pattern compared to AAV-related nephritis without ILD, using data from the Cambridge AAV cohort. Results 135 patients with AAV-ILD were included; 94 (70%) had also kidney involvement, in whom the mean age was 71 ± 11 years and 87% MPO-ANCA positive. The ILD diagnosis preceded AAV in 17%, 64% presented concurrently with kidney involvement, 20% with pulmonary haemorrhage. The most common lung radiological pattern was UIP (67%). At presentation, the median glomerular filtration rate (GFR) was 27 ml/min per 1.73 m2 (interquartile range 12-50), with a median albumin-to creatinine ratio 23 mg/mmol (IQR 10-97). Among 72 patients with available kidney biopsy, the most prevalent Berden class was focal in 45%, followed by mixed in 33%, crescentic in 18% and sclerotic in 4%. Although, the prevalence of Berden classes did not significantly differ between ILD-nephritis and no ILD-nephritis groups, the former group had a higher baseline GFR (p = 0.05), lower albuminuria level (p = 0.002), higher percentage of normal glomeruli (p = 0.027), lower glomerular necrosis percentage (p = 0.002) and higher interstitial fibrosis score (p = 0.049). Within five years, the ILD-nephritis group demonstrated renal recovery, as indicated by an adjusted mean delta GFR of 13.4 ml/min per 1.73 m2, without a significant difference compared to the no ILD-nephritis group. Over a median follow-up of 4.9 years (IQR 2-9), the progression to end-stage kidney disease (ESKD) was comparable between the groups. However, notably, the ILD-nephritis group experienced significantly poorer survival rates (mean 10.9 years vs 17.9 years, log-rank p < 0.001). Conclusion In AAV-ILD, kidney involvement is often characterized by fewer inflammatory and a higher prevalence of fibrotic lesions than on non-ILD-AAV. Despite initial differences in renal pathology and kidney function between these groups, both demonstrated similar risks of progressing to ESKD. Nevertheless, it's crucial to underscore the significant influence of ILD on the overall outcomes of AAV patients with kidney involvement.

#2710 The importance of monitoring creatinine, hematuria, and proteinuria in relation to kidney outcomes in patients with ANCA-associated vasculitis

Abstract Background and Aims Patients with ANCA-associated vasculitis (AAV) often a have kidney involvement and it has been shown that a decreased glomerular filtration rate at entry is associated with a worse outcome both for patient and kidney survival. However, some patients present with a low kidney function at entry, but recover during treatment. Thus, it may be interesting to see if the kidney function after starting treatment is more accurate predicting outcome than the one at entry. The aim of our study was to determine the prognostic significance of proteinuria, hematuria and serum creatinine monitoring in patients with AAV Method The dataset included 848 patients with newly diagnosed AAV who participated in 7 RCTs (1995-2012), and median follow-up time of the entire cohort was 8 years (IQR: 2.9-13.6). Creatinine, hematuria, and proteinuria was recorded at baseline, 3, 6, 9, 12, and 18 months after randomization. Kidney outcome was defined as permanent dialysis dependency during follow-up or kidney transplantation. Receiver operating characteristic curves (ROC) were calculated and screening performance of cut-off scores was evaluated using the Youden Index. A multivariate Cox regression model was performed to examine the factors associated with the kidney outcome. Results Median baseline Creatinine was 176 µmol/L (IQR: 97-388.5), 114 µmol/L (IQR: 88-171) at 3 months, 110 µmol/L (IQR: 89-160) at 6 months, 110 µmol/L (IQR: 89-155) at 12 months, and 102 µmol/L (IQR: 84-132.6) at 18 months. Within 12 months, the AUC of Creatinine was the highest at 0.87 (95% CI: 0.79-0.95; SE: 0.05; p-value: 0.04) to predict kidney outcome. For the cut-off point of 135 µmol/L, 12-month-Creatinine achieved a sensitivity of 83% and specificity of 76% (LR+: 3.35, LR-: 0.23). The ROC curves for hematuria, showed that the highest AUC was found at 9 months (AUC: 0.71; SE: 0.04; 95% CI: 0.64-0.78; p = 0.032) (Fig. 1). Examination of the ROC curve of proteinuria > 0.5/24 h, revealed that the highest AUC corresponded to the baseline determination (AUC: 0.64; SE: 0.08; 95% CI: 0.48-0.80), but there was no statistically significant difference observed among the AUC values of proteinuria across the monitored periods. In the multivariable Cox regression model, MPA diagnosis, creatinine at 12 months, and age > 65 years old were independent prognostic factors for the kidney outcome. The model including Creatinine at 12 months was more robust than the model including baseline Creatinine (Harrell's C: 0.84 and 0.76, respectively) Conclusion The best diagnostic accuracy for ESKD in ROC curves was shown by serum creatinine at 12 months (AUC: 0.87; SE: 0.05; 95% CI 0.79-0.95; p-value: 0.04). Hematuria was a predictor of the kidney outcome of moderate quality (AUC 0.71; SE 0.04; 95% CI: 0.64-0.78), while proteinuria > 0. 5 g/24 h had a modest and non-significant AUC (AUC 0.64; SE 0.08; 95% CI 0.48-0.80). Serum creatinine at 12 months was found to be an independent prognostic factor for kidney outcome, while haematuria and albuminuria during follow up within the first 18 months did not seem to add any impact on outcome. Reevaluation of renal prognosis at 12 months might be useful to reassess treatment in patients with AAV. Taken together, these findings suggest than incorporating biomarker monitoring into clinical-analytical predictive models can provide a more nuanced and accurate method for predicting renal outcomes as the disease progresses.