Pauci-immune Glomerulonephritis Research Articles

Deciphering the association between biopsy-confirmed systemic small vessel vasculitis and Epstein-Barr virus-positive polymorphic B-cell lymphoproliferation.

The Epstein-Barr virus (EBV) is associated with various lymphoproliferative disorders (LPD). Additionally, EBV infection has correlated with diverse autoimmune diseases. However, the association between EBV and systemic small vessel vasculitis (SVV) remains controversial. Here, we report a case of SVV with pauci-immune glomerulonephritis accompanied by an EBV-positive polymorphic B-cell LPD, not otherwise specified. The intricate distinction between EBV-positive B-cell LPD and SVV was difficult, as both diseases demonstrated similar clinical presentations. Lymph node and kidney biopsies facilitated the accurate diagnosis of these two conditions. The administration of high-dose prednisolone, combined with rituximab, proved efficacious, with no instances of relapse over the subsequent 2-year period. This case indicates an association between EBV-positive B-cell LPD and SVV. The diligent execution of biopsies is a crucial diagnostic and interpretive strategy, generating precise comprehension of this condition and guiding its appropriate therapeutic management.

#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.

Kidney Failure in Pauci-immune Crescentic Glomerulonephritis: Rationale for Immunosuppression to Improve Kidney Outcome.

Pauci-immune crescentic glomerulonephritis is the hallmark finding in ANCA-associated vasculitis (AAV) when the kidneys are affected. The rationale for immunosuppression in AAV is based on the underlying autoimmune nature of the disease. Overall remission rates, kidney outcomes, and the burden of disease have greatly improved since the discovery of various immunosuppressive therapies, but relapses remain common, and a significant proportion of patients continue to progress to end-stage kidney disease. Here, we review the role of immunosuppressive therapies for the treatment of pauci-immune crescentic glomerulonephritis. Besides the recognized role of B and T cells in the pathogenies of AAV, the focus on the contribution of inflammatory cytokines, neutrophil extracellular traps (NETs), and the complement system allowed the discovery of new therapies. Specifically, the C5a receptor blocker (avacopan) has been approved as a glucocorticoid-sparing agent. Additionally, based on observational data, more clinicians are now using combination therapies during the induction phase. There is also an evolving understanding of the role of plasma exchange in removing ANCA antibodies. Furthermore, the recent development of risk score systems provides physicians with valuable prognostic information that can influence decisions on immunosuppression, although future validation from larger cohorts is needed. The over-activation of various immune pathways plays a significant role in the pathogenesis of pauci-immune crescentic glomerulonephritis in AAV. Immunosuppression is, therefore, an important strategy to halt disease progression and improve overall outcomes. Relapse prevention while minimizing adverse events of immunosuppression is a major long-term goal in AAV management.

Myeloperoxidase-Associated Membranous Nephropathy in Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis

IntroductionAnti-neutrophil cytoplasmic antibody (ANCA)–associated glomerulonephritis (GN) is characterized by pauci-immune crescentic GN. Although myeloperoxidase ANCA-associated GN (MPO-ANCA GN) with membranous nephropathy (MN), where bright granular capillary myeloperoxidase (MPO) and immunoglobulin G (IgG) staining along the glomerular basement membrane (GBM) is present, has been reported; however, its clinicopathological features remain unclear. MethodsWe investigated 7 MPO-ANCA GN with MN and 11 control cases (6 MPO-ANCA GN and 5 primary MN cases). Proteomics of laser microdissected glomeruli followed by immunohistochemical analysis was performed to identify causal antigens in MPO-ANCA GN with MN. We described the clinicopathological features of MPO-associated MN compared with those of MPO-ANCA GN and primary MN. ResultsWe detected proteomic MPO and granular capillary MPO deposits in all MPO-ANCA GN with MN cases. Confocal microscopy revealed MPO and IgG co-localization along the GBM. MPO-associated MN clinicopathological features include greater proteinuria, a higher fibrous crescent rate, and a lower MPO-ANCA titer than MPO-ANCA GN. The estimated glomerular filtration rate and urinary protein excretion were lower in MPO-associated MN than in primary MN. ConclusionMPO-associated MN, a unique type of secondary MN where MPO serves as the causal antigen, is a subset of MPO-ANCA GN with MN. Prolonged periods of MPO-ANCA GN and a low MPO-ANCA titer might be related to MPO-associated MN development.

Glomerulonephritis following COVID-19 infection or vaccination: a multicenter study in South Korea.

Despite the widespread impact of the severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) and vaccination in South Korea, our understanding of kidney diseases following these events remains limited. We aimed to address this gap by investigating the characteristics of glomerular diseases following the COVID-19 infection and vaccination in South Korea. Data from multiple centers were used to identify de novo glomerulonephritis (GN) cases with suspected onset following COVID-19 infection or vaccination. Retrospective surveys were used to determine the COVID-19-related histories of patients who were initially not implicated. Bayesian structural time series and autoregressive integrated moving average models were used to determine causality. Glomerular diseases occurred shortly after the infection or vaccination. The most prevalent postinfection GN was podocytopathy (42.9%), comprising primary focal segmental glomerulosclerosis and minimal change disease, whereas postvaccination GN mainly included immunoglobulin A nephropathy (IgAN; 57.9%) and Henoch-Schönlein purpura nephritis (HSP; 15.8%). No patient progressed to end-stage kidney disease. Among the patients who were initially not implicated, nine patients with IgAN/HSP were recently vaccinated against COVID-19. The proportion of glomerular diseases changed during the pandemic in South Korea, with an increase in acute interstitial nephritis and a decrease in pauci-immune crescentic GN. This study showed the characteristics of GNs following COVID-19 infection or vaccination in South Korea. Understanding these associations is crucial for developing effective patient management and vaccination strategies. Further investigation is required to fully comprehend COVID-19's impact on GN.

Identification of inflammatory biomarkers in IgA nephropathy using the NanoString technology: a validation study in Caucasians

Objective and designImmunoglobulin A nephropathy (IgAN) is a kidney disease characterized by the accumulation of IgA deposits in the glomeruli of the kidney, leading to inflammation and damage to the kidney. The inflammatory markers involved in IgAN remain to be defined. Gene expression analysis platforms, such as the NanoString nCounter system, are promising screening and diagnostic tools, especially in oncology. Still, their role as a diagnostic and prognostic tool in IgAN remains scarce. In this study, we aimed to validate the use of NanoString technology to identify potential inflammatory biomarkers involved in the progression of IgAN.SubjectsA total of 30 patients with biopsy-proven IgAN and 7 cases of antineutrophil cytoplasmic antibody (ANCA)-associated pauci-immune glomerulonephritis were included for gene expression measurement. For the immunofluorescence validation experiments, a total of 6 IgAN patients and 3 controls were included.MethodsTotal RNA was extracted from formalin-fixed paraffin-embedded kidney biopsy specimens, and a customized 48-plex human gene CodeSet was used to study 29 genes implicated in different biological pathways. Comparisons in gene expression were made between IgAN and ANCA-associated pauci-immune glomerulonephritis patients to delineate an expression profile specific to IgAN. Gene expression was compared between patients with low and moderate risk of progression. Genes for which RNA expression was associated with disease progression were analyzed for protein expression by immunofluorescence and compared with controls.ResultsIgAN patients had a distinct gene expression profile with decreased expression in genes IL-6, INFG, and C1QB compared to ANCA patients. C3 and TNFRSF1B were identified as potential biomarkers for IgAN progression in patients early in their disease course. Protein expression for those 2 candidate genes was upregulated in IgAN patients compared to controls. Expression of genes implicated in fibrosis (PTEN, CASPASE 3, TGM2, TGFB1, IL2, and TNFRSF1B) was more pronounced in IgAN patients with severe fibrosis compared to those with none.ConclusionsOur findings validate our NanoString mRNA profiling by examining protein expression levels of two candidate genes, C3 and TNFRSF1B, in IgAN patients and controls. We also identified several upregulated mRNA transcripts implicated in the development of fibrosis that may be considered fibrotic markers within IgAN patients.

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.

Assessment of some cytokines levels in a pauci-immune crescentic glomerulonephritis patients

Background: Glomerulonephritis is the common cause of end-stage of renal failure. Rapidly progressive glomerulonephritis (RPGN) is characterized by glomerular injuries and formation of crescents. Moreover, anti-neutrophil cytoplasmic antibodies (ANCA), and pro-inflammatory cytokines play a damaging role in a crescent glomerulonephritis. Objectives: The main goal of the current study was aimed to determine the ANCA autoantibodies, and the serum levels of pro-inflammatory cytokines (IL-6, IL-17, IL-18, INF-γ), as well as the relationship between these cytokines and ANCA test in a pauci-immune crescentic glomerulonephritis patients. Methodology: The study was carried out in AL-Yarmouk teaching hospital and AL-Sader teaching hospital during the period from April 2022 to April 2023. This study was involved 90 patients with a crescentic glomerulonephritis disease, the diagnosis was made by the consultant medical staff. In addition to a 60 samples of healthy individuals as control group was involved to comparison the results. ANCA test was made by Indirect immunofluorescence method for the detection of ANCA autoantibodies in serum, in addition to measure the serum level of cytokines including IL6, IL-17, IL-18, and IFN-γ by using Enzyme Linked Immune Sorbent Assay methods. Results: This study has shown that the majority of patients were male (66.7%). Moreover, the most effected age groups within the age ≥ 61 years in percentage (65.5%) followed by the age group 51-60 years old (28.8%). There were 59 (65.5%) positive cases for ANCA from total patients and all of these cases were MPO-ANCA. The total RPGN patients were showed a highly significant increased mean serum levels of IL-18, IL-17, IL-6, and INF-γ as compared to healthy controls, as well as, the same cytokines were showed significant increased levels in myeloperoxidase (MPO)-ANCA positive serum in crescent glomerulonephritis patients as compared to ANCA –negative serum of patients. These results indicate a functional role of IL-6, IL-17, IL-18, and INF-γ in ANCA-mediated neutrophil activation by the interdependence of IL-6, IL-17, IL-18, and INF-γ priming for ANCA responses. Conclusion: It can be drawn from the present study that, the pro-inflammatory cytokines play an integral role in determining the course of disease and it can be used as major drug targets for therapy, as well as these cytokines have the ability to priming neutrophils thus contribute in the progression of a pauci-immune crescentic glomerulonephritis disease.

Pneumorenal Syndrome Complicating ANCA-Negative Pauci-Immune Vasculitis Associated with Atypical Mycobacteriosis: Case Report

Among the forms of pneumorenal syndrome (PRS), one of the most urgent is characterized by the combination of diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis (RPGN). In 90% of cases, it is the manifestation of an autoimmune disease, such as pauci-immune vasculitis with anti-neutrophil cytoplasmic antibodies (ANCA) or Goodpasture's disease with the presence of antibodies directed against the basement membrane of the glomerular and alveolar capillaries (anti-GBM). These antibodies are absent in approximately 10% of cases with histological confirmation in the context of rare clinical situations. We report a case of a 66-year-old patient, with a history of alcoholism and active smoking, who was admitted to the hospital for respiratory distress with hemoptysis. The admission assessment showed severe renal failure requiring hemodialysis upon admission. ANCA and anti-GBM, as well as all other autoantibodies were negative. A renal biopsy revealed pauci-immune extra-capillary glomerulonephritis with the majority of chronic lesions. The orientation of the diagnostic approach in search of other causes of pauci-immune vasculitis with negative antibodies has been initiated. He was treated with glucocorticoids in combination with cyclophosphamide. The initial evolution was marked by the improvement of respiratory symptoms and a less considerable recovery of renal function. PRS can develop without the presence of ANCA or other autoantibodies. The diagnosis is then made by histology. Renal damage, such as extra-capillary glomerulonephritis (GN), is more severe and has a very poor prognosis with a high risk of mortality. The absence of ANCA should never delay diagnosis and treatment.

Acute interstitial nephritis caused by ANCA-associated vasculitis: a case based review.

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) typically manifests as rapidly progressive glomerulonephritis with crescent formation. In this report, we present a local case of myeloperoxidase (MPO)-AAV-associated acute interstitial nephritis (AIN), showing slight pauci-immune glomerulonephritis and positive MPO-ANCA. This case is characterized by foot process effacement of podocytes in the glomerulus, a favorable prognosis, and an absence of crescentic formation. To further understand this condition, we conducted a comprehensive literature search on Google Scholar and PubMed, employing both free text words and MeSH terms related to "AAV and AIN." This search yielded 24 cases, which we analyzed for their clinical features, laboratory findings, renal pathological characteristics, and therapeutic outcomes. AAV-associated interstitial nephritis predominantly affects elderly patients and is often associated with anemia, proteinuria, hematuria, and nonspecific manifestations, including fever, anorexia, fatigue, edema, and weight loss. Most of the cases in our review were MPO-ANCA-positive and exhibited isolated interstitial inflammation. These patients typically presented with relatively lower levels of serum creatinine, 24-h urine protein levels, and MPO-ANCA titers. All patients in our study received immunosuppressive therapy, including glucocorticoids, immunosuppressants, and rituximab, with the majority achieving clinical remission. Isolated AIN in the context of AAV is a rare occurrence, but it displays distinct clinical, laboratory, and pathological features. Patients with this presentation show a positive response to immunosuppressive treatment. Nevertheless, the establishment of definitive therapy guidelines for AAV-associated AIN remains uncertain and necessitates further investigation to develop comprehensive treatment guidelines. AIN, particularly when lacking typical glomerulus lesions, may represent a novel subgroup within MPO-AAV warranting additional research and clinical attention. Key Points • This study contributes valuable scientific insights by highlighting that MPO-AAV-associated interstitial nephritis, even without crescentic formation, can exhibit podocyte foot process effacement and respond well to treatment. • The presence of AIN, independent of crescentic glomerulonephritis, suggests the potential emergence of a new subclass within MPA-AAV. • Notably, some cases of MPO-AAV-associated AIN may present with normal levels of Scr (Table 5, cases 5, 6, and 17). • This observation highlights the importance of considering renal biopsy, diagnosis, and therapy in a timely manner to prevent the development of chronic kidney disease (CKD).

Anti-Glomerular Basement Membrane Disease Overlap with Pauci-Immune Glomerulonephritis: Temporal Concurrence at a Single Center

Anti-Glomerular Basement Membrane Disease Overlap with Pauci-Immune Glomerulonephritis: Temporal Concurrence at a Single Center

A Case of Possible Malignancy-Related Polyangiitis Overlap Syndrome with Henoch-Schönlein Purpura and ANCA-Negative Pauci-Immune Glomerulonephritis as a Manifestation of Neuroendocrine Cancer

A Case of Possible Malignancy-Related Polyangiitis Overlap Syndrome with Henoch-Schönlein Purpura and ANCA-Negative Pauci-Immune Glomerulonephritis as a Manifestation of Neuroendocrine Cancer

Rapidly Progressive Renal Failure in Type 2 Diabetic versus Non-diabetic Patients: Changing Trends, Natural History, and Outcome in an Indian Tertiary Care Center.

Rapidly progressive renal failure (RPRF) is not typical of diabetic nephropathy and suggests non-diabetic kidney disease (NDKD). We conducted an analysis of the data of RPRF patients (28 diabetic and 88 non-diabetic patients) with doubled creatinine over 2 weeks to 3 months and/or presented with >4 mg serum creatinine without prior renal disease to ascertain the types of lesions and compare the patients' histopathology. The primary outcome was dependence on dialysis at 1 year. Anti-neutrophilic cytoplasmic antibody-associated pauci-immune glomerulonephritis was the most common cause of RPRF in both groups. No particular lesion was more frequent in either group. Dependence on dialysis at 1 year was similar in both groups and was associated with dependence on dialysis at presentation but not diabetes. Crescentic glomerulonephritis was the most common in non-diabetic patients (57.9 vs. 25%, P = 0.002), and acute tubular necrosis (ATN) was seen in diabetic patients (21.4 vs. 11.4%, P = 0.179). Both factors were associated with adverse renal outcomes. Diffuse global glomerulosclerosis at presentation suggested a poor outcome in both groups. Diabetic nephropathy was seen in 14.29%, and its presence did not affect the outcome. The etiology of RPRF in diabetic patients has changed and is similar to that in non-diabetic patients, with no specific lesions predominating. Diabetic nephropathy does not alter the outcome for those with RPRF. Diffuse global glomerulosclerosis, being on dialysis at presentation, and ATN in a diabetic patient indicate a poor outcome and need close follow-up. Diabetic retinopathy should not prevent us from investigating for NDKD.

Rapidly progressive glomerulonephritis and ANCA-negative pauci-immune vasculitis: an unusual presentation. A case report

Rapidly progressive glomerulonephritis corresponds to a clinical scenario of glomerular damage involving rapid deterioration of renal function with multiple etiologies. Within these, 85 % of cases are associated with pauci-immune vasculitis with antineutrophil cytoplasmic antibodies (ANCA). However, a remaining subgroup may present ANCA-negative results. The clinical presentation often involves a decline in the glomerular filtration rate, sometimes requiring renal replacement therapy, as well as extrarenal manifestations such as diffuse alveolar hemorrhage. Confirmatory diagnosis is achieved through renal biopsy, negative serology for ANCA, and exclusion of other etiologies. According to international clinical practice guidelines, the recommended treatment for both entities is the same, with the addition of renal replacement therapy if necessary. However, the prognosis tends to be unfavorable with little to no recovery of renal function. This case presents a female patient in the early decades of life with ANCA-negative, rapidly progressive, pauci-immune glomerulonephritis.

Renal involvement in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing vasculitis, which typically affects small-to medium-sized blood vessels. It is characterized by the presence of tissue infiltrates rich in eosinophils, along with the formation of granulomatous lesions. About 40% of cases have positive anti-neutrophil cytoplasm antibodies (ANCA), with predominant perinuclear staining, and anti-myeloperoxidase (anti-MPO) specificity in about 65% of cases. Typical manifestations of EGPA include the late onset of asthma, nasal and sinus-related symptoms, peripheral neuropathy, and significant eosinophilia observed in the peripheral blood. In contrast to granulomatosis with polyangiitis and microscopic polyangiitis, renal involvement in EGPA is less frequent (about 25%) and poorly studied. Necrotizing pauci-immune crescentic glomerulonephritis is the most common renal presentation in patients with ANCA-positive EGPA. Although rarely, other forms of renal involvement may also be observed, such as eosinophilic interstitial nephritis, mesangial glomerulonephritis, membranous nephropathy, or focal sclerosis. A standardized treatment for EGPA with renal involvement has not been defined, however the survival and the renal outcomes are usually better than in the other ANCA-associated vasculitides. Nonetheless, kidney disease is an adverse prognostic factor for EGPA patients. Larger studies are required to better describe the renal involvement, in particular for patterns different from crescentic glomerulonephritis, and to favor the development of a consensual therapeutic approach. In this article, in addition to personal data, we will review recent findings on patient clinical phenotypes based on ANCA, genetics and the impact of biological drugs on disease management.

Comparison of Clinico-pathologic features and outcomes of ANCA negative and ANCA positive pauci immune crescentic glomerulonephritis: A single centre study.

Pauci-immune crescentic glomerulonephritis (PICN) is an important cause of rapidly progressive renal failure. 10-40% of PICN cases have ANCA (antineutrophil cytoplasmic antibody) negative serology. The present study compared clinico-pathologic features, Brix's renal risk score, Berden's histopathological classes and differences in outcome between ANCAnegative vs ANCA positive PICN patients. Sixty-one patients of biopsy-proven PICN were studied. Biochemical findings and ANCA serology were recorded. Renal biopsy slides were reviewed along with direct immunofluorescence. Clinical and histological features were compared between ANCA negative and positive PICN using the Man Whitney U test and Chi-square test. Patients were compared for distribution in Berden's histological classes and Brix's renal risk categories. Patient and renal survival were compared using Kaplan-Meier survival analysis. ANCA negative PICN patients were younger (44.9 ± 16.5 years vs 53.6 ± 15.1 years, P = 0.049). Nasal (0 vs 18%, P = 0.035) and pulmonary involvement (9% vs 38%, P = 0.014) were lower in ANCA negative group. Both ANCA groups had similar renal biochemical profiles, percentage normal glomeruli, 16.3 ± 18.2 vs 21.7 ± 20.4 and percentage glomeruli with crescents, 64.5 ± 28.1 vs 64.3 ± 27.1. Twenty-seven per cent of ANCA negative cases fell in the sclerotic class in Berden's classification vs just 2.5% in ANCA positive group (p = 0.037) without significant difference in Brix's renal risk categories (p = 0.329). Thirteen per cent of ANCA negative patients achieved complete remission on treatment compared to 33% in ANCA positive patients. Patient survival and overall probability of progressing to ESRD were similar in the two groups. ANCA negative PICN cases present at younger ages. Nasal and pulmonary involvement is uncommon in these patients. Patient survival and progression to ESRD are similar in both ANCA groups.

#5598 MULTICENTER STUDY TO ASSESS THE FREQUENCY OF ADVERSE EVENTS FROM VACCINATION AGAINST SARS-COV2 IN PATIENTS WITH PAUCI-IMMUNE GLOMERULONEPHRITIS

Abstract Background and Aims The present study aims to investigate the frequency of adverse events of SARS-CoV2 vaccination in patients with pauci-immune glomerulonephritis. Method Patients with pauci-immune glomerulonephritis who were vaccinated with the SARS-CoV2 vaccine were retrospectively studied. Patients who had reached end-stage kidney disease before the vaccine were excluded. The histopathological diagnosis of pauci-immune glomerulonephritis, immunosuppressive regimens, resulting outcome, timing, doses, adverse effects of the vaccine and its potential effect on the clinical course of pauci-immune glomerulonephritis were recorded. Results To date, 67 patients with pauci-immune glomerulonephritis with a mean age of 59.6 (±17.5) years have been included in the study, of whom 36 (53.7%) were females. 34 (50.7%) of the patients had a medical history of arterial hypertension and 16 (23.9%) of diabetes mellitus with an average duration of 9 and 10 years respectively. 66 (98.5%) received induction therapy and 87.7% achieved remission. 50 (74.6%) received maintenance therapy and 50 (94.3%) were vaccinated against SARS-CoV2 at a mean time of 79.5 (±70.8) months from diagnostic biopsy with 3.2 (± 1.0) doses. 90% of patients were in remission and 44% were receiving immunosuppressive therapy at the time of vaccination. 26% of patients reported systemic adverse events related to vaccination and 62% local reactions at the administration site. 2 (4.3%) patients experienced pauci-immune glomerulonephritis relapse with a mean time to relapse of 5.7 (±3.4) months from the 1st dose. Conclusion Based on the results from this cohort of patients with pauci-immune glomerulonephritis, the SARS-CoV2 vaccine appears safe, with no significant impact on the likelihood of pauci-immune glomerulonephritis relapse for patients in remission.

#6930 TOO ELDERLY FOR A KIDNEY BIOPSY?

Abstract Background and Aims As we age, we lose kidney function and accumulate risk factors and comorbidities that predispose to kidney damage. However, kidney disease can develop at any time. Life expectancy continues to improve worldwide. For that reason, more elderly patients are undergoing diagnostic kidney biopsies (KB). There is a general reluctance in performing KB in those patients. It is important to know if a diagnosis KB in elderly patients can have a positive therapeutic impact. Method In this retrospective cohort study, we analyzed the medical charts of all patients aged ≥ 80years who underwent a native kidney biopsy (KB) between January and December 2021, in a central hospital in Portugal. Results Between January and December 2021, 59 patients underwent a native KB, 6 of them over 80 years of age (10% of all patients). Between those elderly patients, the median age was 82 years. The indications for KB were chronic kidney disease with a nephrotic range proteinuria in 3 patients, nephrotic syndrome, acute glomerulonephritis and acute kidney injury in 1 patient each. Median serum creatinine was 2.27 mg/dL (minimum 0.8 and maximum 5.4 mg/dL) and median protein-to-creatinine ratio was 5.7g/g (minimum 3.3 and maximum 13g/g). The pathological diagnoses found were focal and segmental glomerulosclerosis (FSGS) (n=2), pauci-immune crescentic glomerulonephritis (n=1), membranous nephropathy in a patient with a follicular lymphoma (n=1), acute interstitial nephritis (AIN) (n=1), and diabetic glomerulosclerosis in a patient with a monoclonal gammopathy of undetermined significance (n=1). 3 patients have received a kidney-specific treatment – the patient with AIN started corticosteroids, one patient with FSGS was submitted to corticosteroids plus tacrolimus, and the patient with pauci-imune crescentic glomerulonephritis to corticosteroids plus rituximab. The patient with membranous nephropathy and follicular lymphoma received a specific chemotherapy regimen according with lymphoproliferative disease. An improvement in kidney function occurred only in one patient and the other three developed adverse effects (particularly corticosteroids induced diabetes and infections). One year later, one of patients who received treatment was dead, another one was on hemodialysis, and the other two patients had a glomerular filtration rate lower than 15mL/min/1.73 m2. Conclusion Elderly patients have a higher risk of adverse effects from the kidney-specific treatment. It is important to assess the therapeutic risk/benefit when considering performing a renal biopsy in these patients.

#4710 CYCLOPHOSPHAMIDE INDUCTION TREATMENT IN ANCA-ASSOCIATED VASCULITIS WITH RENAL AND PULMONARY INVOLVEMENT: OUTCOMES AND SIDE EFFECTS

Abstract Background and Aims ANCA associated vasculitis are necrotaizing vasculitis of small and medium vassels - which cause organ damage. They are relatively rare diseases with an estimated prevalence of 200–400 cases per million people [1]. Pauci-immune necrotizing and crescentic glomerulonephritis (GN) is a frequent component of ANCA-associated vasculitis that can cause rapidly progressive Acute Kidney Injury (AKI). Less frequently, it can cause low progressive Chronic Kidney Disease (CKD) [2]. Combination therapy of steroids and cyclophosphamide has improved 5-years survival up to 70-90% but it can cause serious side effects including infectious episodes [3], bone marrow suppression and myelodysplasia. We present a case highlighting treatment modalities and our decision making. Method Our retrospective study analyzes the case of a 63-year-old male presenting with progressive dyspnea and hemoptysis. A chest CT suggested diffuse alveolar hemorrhage. The blood tests showed onset of AKI with 7.68 mg/dl serum creatinine (normal values 0.72-1.25), mild proteinuria and hematuria. A kidney and pulmonary vasculitis was suspected and the c-ANCA serum value was elevated at >500 IU/ml. Three cycles of Plasma Exchange (PEX) were performed and methylprednisolone was given (500 mg for 3 days, 1 g on the 4th day) followed by cyclophosphamide boluses of 1 g/week for 4 weeks. Broad-spectrum antibiotics and antifungal therapy was administered to prevent secondary infections. Due to the further worsening of the renal function, three hemodialysis treatments and a cascade filtration were performed continuing with cyclophoshamide 1 g/day orally and methylprednisolone 60 mg/day. Cyclophosphamide therapy was discontinued due to thrombocytopenia and progressive leukopenia. Filgastrim 30MU/0.5 ml was administered for five days until the resolution of the pancytopenia when cyclophosphamide 50 mg 2cp+1cp was resumed. Results A one-month follow-up CT showed reduction in hemorrhagic opacities and the c-ANCA level was significantly reduced. Steroid dosing was progressively reduced and the patient was discharged with methylprednisolone 16mg 2cp+1/2cp tapering over 6 months and cyclophosphamide 50 mg 2cp+1cp. Serum creatinine levels improved from 2.64 mg% at discharge to 1.6 mg% at follow up. Conclusion When treating c-ANCA vasculitis with corticosteroids and cyclophosphamide, routine evaluation of complete blood count parameters is necessary to prevent bone marrow toxicity. We continued methylprednisolone and cyclophosphamide for six months, obtaining a total clinical remission despite side effects induced by the state of immunosuppression (oral cavity mycosis, bone marrow toxicity and CMV reactivation).

#6178 ANCA-ASSOCIATED VASCULITIS FOLLOWING PFIZER-BIONTECH COVID-19 VACCINE: TRUE ASSOCIATION OR CIRCUMSTANTIAL?

Abstract Background and Aims Antineutrophil cytoplasmatic antibody (ANCA)- associated vasculitis (AAV) is a small vessel vasculitis hallmarked by the presence of antibodies against antigens in cytoplasmic granules of neutrophils. Vaccines per se stimulate the immune system, including the innate and the adaptive immune response. Therefore, it is possible that an excess of autoimmunity is observed after vaccine administration. Vaccination (notably influenza) is a recognized trigger for the relapse of ANCA-associated vasculitis. ANCA associated vasculitis and autoimmune reactions have been reported with COVID-19 infection and following vaccination. Results We report the case of a Caucasian, 62 year-old-man, with a previous history of type 2 diabetes mellitus, hypertension and atrial fibrillation. Blood analysis one year before presentation showed preserved renal function and normal urinalysis. He received the first dose of Pfizer-BioNTech COVID-19 vaccine and two weeks later routine blood analysis showed acute kidney injury with serum Creatinine 1.75 mg/dL with de novo hematuria, a protein to creatinine ratio (RPC) 1.1 mg/g and candersartan (4 mg twice daily) was started. The patient received the second dose of COVID-19 vaccine 21 days after the first injection. Two weeks later he developed anorexia, nausea and de novo hematuria. He was admitted at the emergency department with deteriorating renal function with a sCr of 5.5 mg/dL, worsening hematuria with dysmorphic red blood cells and proteinuria (RPC 2.9 mg/g). Renal ultrasound was normal. Immunological studies revealed an elevated ANCA-MPO titer of 561. A kidney biopsy was performed and showed a crescentic necrotizing glomerulonephritis. Immunofluorescence confirmed pauciimmune glomerulonephritis. He was diagnosed with renal limited myeloperoxidase (MPO) ANCA AAV. He started 3 pulses of 500mg I.V methylprednisolone followed by prednisolone 1 mg/kg/day after that. He also started rituximab (4 doses of 500mg I.V once week apart). Despite the immunosuppression, the patient never recovered renal function and remained dialysis dependent. Conclusion Whether autoimmune diseases can be triggered after vaccination remains a matter of discussion among experts. ANCA associated vasculitis and autoimmune reactions have been reported with COVID-19 infection and following vaccination, which prompts the question whether this response could be a direct reaction to the RNA present in the vaccine. While an association with de novo ANCA vasculitis and COVID-19 vaccine may be possible, further investigation is necessary.