anti-GBM Research Articles

Crescentic Glomerulonephritis (GN) with Anti-glomerular Basement Membrane (GBM) Antibodies and ANCA: Double Trouble

Crescentic Glomerulonephritis (GN) with Anti-glomerular Basement Membrane (GBM) Antibodies and ANCA: Double Trouble

Atypical Anti-GBM with ANCA Vasculitis- A Rarest of the Rare Entity: Index Case from Eastern India

Anti-glomerular basement membrane (GBM) antibody glomerulonephritis is an extremely rare glomerular disease. Around 90% of the patients are positive for serum anti-GBM antibodies while up to 10% can be negative. In such patients, only a kidney biopsy can reveal the anti-GBM disease it is then labeled as an atypical anti-GBM disease. Though anti-GBM disease can be associated with Anti Neutrophil Cytoplasmic Antibodies (ANCA) positivity, it is extremely rare to find atypical anti-GBM with ANCA positivity so much so that till now there are very few such cases reported from across the world. The case presented here is one such case where the patient presented with adult-onset nephrotic syndrome features with active urinary sediments and mildly deranged renal function. Myeloperoxidase (MPO) ANCA was positive and it was considered ANCA-associated crescentic glomerulonephritis (GN) but after the renal biopsy the picture was of anti-GBM disease. She was treated with pulse methylprednisolone but her creatinine increased in the meantime and considering anti-GBM she was put on Plasma Exchange (PLEX). She received 5 sessions of PLEX after which her renal function improved. She was also planned for Rituximab which could not be given due to local infection. As there are no protocols for treating such cases because of the extremely rare nature of the presentation, this case will increase the understanding of such presentations for the clinicians. This will help to plan for building the approach for such cases.

Anti-Glomerular Basement Membrane Antibody Disease: Clinicopathologic Profile and Outcomes

Background: Anti-glomerular basement membrane antibody disease is a rare autoimmune disease caused by antibodies to α3 chain of type 4 collagen. Patients presenting with severe renal involvement requiring dialysis have poor response to treatment. Materials and Methods: We conducted a retrospective and prospective study at Institute of Nephrology, Madras Medical College, Chennai, India by analyzing the data of patients with biopsy-proven anti-GBM antibody disease treated from January 2013 to December 2019. Results: There were 2,949 kidney biopsies in the study period and 92 showed crescentic glomerulonephritis (GN). Of those, 20 patients (10 males) had anti-GBM antibody disease. Mean age was 40.75 ± 14.75 years. Rapidly progressive renal failure was the most common mode of presentation (95%); five (25%) patients had diffuse alveolar hemorrhage (DAH) and nineteen patients (95%) required dialysis at presentation. Seven patients (35%) were positive for anti-neutrophil cytoplasmic antibody (anti-myeloperoxidase in six and anti-proteinase 3 in one). Of the twelve patients (60%) who received immunosuppression (cyclophosphamide, steroids, and plasma exchange), two patients (10%) attained remission, and two patients (10%) expired due to sepsis. Crescentic GN was the predominant pathology in kidney biopsy in 19 patients (95%). Mesangial hypercellularity with deposition of IgA and C3 in mesangium was present in one patient. Conclusion: In our study, anti-GBM antibody disease accounted for 21.7% of crescentic GN. Majority of patients presented late, requiring dialysis. Patient survival was 90%, while renal survival was only 10%. One patient had co-occurrence of IgA nephropathy with anti-GBM antibody disease.

Anti-GBM antibody in a patient with diabetic nephropathy; all that glitters is not gold.

We present the case of a 58-year-old male diabetic patient admitted to our department for a slight decrease in kidney function, with nephrotic range proteinuria, hematuria (16,000/ml) and positive anti-glomerular basement membrane antibodies. Kidney biopsy revealed diabetic nephropathy with no evidence of crescent formation or linear immunoglobulin deposits along the basement membrane. We discuss the various clinical settings involving positive anti-glomerular basement membrane in the absence of crescentic glomerulonephritis.

#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.

#1155 Outcomes after kidney transplantation in anti-glomerular basement membrane disease

Abstract Background and Aims Anti-glomerular basement membrane antibody disease-associated glomerulonephritis (anti-GBM-GN) can lead to end-stage kidney disease (ESKD), requiring replacement therapy with dialysis or kidney transplant (KT). Few studies evaluated the outcome of these patients after KT. Our aim was to describe, in comparison with a control group, the occurrence of the following events: delayed graft function recovery, graft survival, relapse, acute rejection, overall survival; and to study the risk factors associated with these events. Method This was a retrospective, multicenter (6 French centers), observational study including patients who received a KT between 2005 and 2023 for ESKD secondary to anti-GBM-GN. Each vasculitis case receiving a KT was matched with 2 controls, matched on gender, center, recipient age (±5 years) and transplant period (±1 year). Event-free survival and the associated risk factors were analyzed. Results 126 patients were included, including 42 with anti-GBM-GN and 84 control patients. The median post-KT follow-up for vasculitis patients was 95 months. There was no difference in the occurrence of DGF between the groups (24 vs 18%, p = 0.5). There was no difference in graft survival when comparing both groups (78% vs 82% at 10 years, p = 0.48) (Fig. 1A). Only one patient experienced a relapse after KT (being anti-GBM negative at the time of transplantation). There was no difference in the incidence of acute rejection between the groups (p = 0.82). There was no difference in overall survival when comparing both groups (83% vs 89% at 10 years, p = 0.76) (Fig. 1B). Conclusion Kidney transplantation is an interesting option for patients with anti-GBM-GN: outcomes are similar to those of a matched population with similar occurrence of acute rejection, graft loss or death. Moreover, relapse rate is low. Comparison with a matched anti-GBM-GN population remaining on dialysis would be of interest to go further.

Atypical anti-glomerular basement membrane disease with membranous hyperplasia: diagnostic challenges and treatment variability

This case report presents a detailed analysis of a 31-year-old male patient who presented with a complex array of clinical symptoms, including proteinuria, hematuria, edema, and kidney insufficiency. Despite undergoing multiple tests, the results for anti-glomerular basement membrane antibodies yielded negative findings. Subsequently, kidney biopsy pathology revealed a distinct diagnosis of atypical anti-glomerular basement membrane (anti-GBM) disease with membrane hyperplasia. Treatment was initiated with a comprehensive approach involving high doses of corticosteroids therapy and cyclophosphamide (CTX). However, contrary to expectations, the patient’s kidney function exhibited rapid deterioration following this therapeutic regimen. The culmination of these complications necessitated a pivotal transition to maintenance hemodialysis. This case underscores the intricate challenges associated with diagnosing and managing rare and atypical presentations of kidney disorders. The negative anti-GBM antibody results and subsequent identification of atypical anti-GBM nephropathy highlight the need for tailored diagnostic strategies to discern subtle nuances within complex clinical scenarios. Additionally, the unexpected response to the treatment regimen emphasizes the potential variability in individual patient responses, underlining the necessity for vigilant monitoring and adaptable treatment strategies. This case report contributes to the evolving understanding of atypical kidney pathologies and the complexities involved in their management.

Laboratory diagnostics for vasculitis beyond antineutrophil cytoplasmatic autoantibodies

The diagnosis of systemic vasculitis (SV) is amajor clinical challenge due to the very different forms of presentation and requires an interdisciplinary approach. Targeted laboratory diagnostics support making the diagnosis, differential diagnosis and classification and are also akey component in the detection of active organ manifestations and treatment complications. The basic laboratory tests include the erythrocyte sedimentation rate (ESR), C‑reactive protein (CRP), blood count, serum creatinine, urinalysis, specific autoantibodies, complement, immunoglobulins, cryoglobulins and hepatitisB and C serology. Antineutrophil cytoplasmic autoantibodies (ANCA), antiglomerular basement membrane antibodies (anti-GBM antibodies) and anti-C1q antibodies are valuable laboratory markers for the diagnosis of the various forms of small vessel vasculitis. There are no specific laboratory tests for the diagnosis of medium and large vessel vasculitis. Despite advances in our understanding of the pathogenesis of vasculitis, no biomarkers have yet been identified that can be reliably used to guide treatment or that are useful in distinguishing vasculitis from other inflammatory diseases such as infections or treatment complications.

Infective Endocarditis Caused by Streptococcus sanguinis Resulting in Stroke, Ruptured Infected Pseudoaneurysm of Superior Mesenteric Artery, and Rapidly Progressive Glomerulonephritis.

A 71-year-old-man was admitted to our hospital with a cerebral embolism and diagnosed with infective endocarditis (IE) caused by Streptococcus sanguinis. Mitral valve replacement was performed. About one month later, he experienced sudden abdominal pain and shock due to a ruptured infected mesenteric artery pseudoaneurysm. Forty-four days after abdominal surgery, he presented with rapidly progressive glomerulonephritis with anti-glomerular basement membrane antibodies. He was treated with plasma exchange and prednisolone, and his renal function gradually improved. Since postoperative complications often occur within a few years after surgery for IE, careful follow-up is important, even after antimicrobial therapy and valve surgery.

A Rare Case of Double-antibody-positive Renal Vasculitis: Are we in a Hurry to Start Tuberculosis Medicines?

Double antibody positive renal vasculitis (anti GBM antibody and pANCA) is a rare form of small vessel vasculitis associated with poor outcome. It is difficult to decide which antibody is the precursor in these cases. We report here such a rare case of double antibody positive renal vasculitis which was started on anti tubercular medicine for a positive mantoux test and interferon gamma release assay. The possible reasons for these antibodies in this may be a complication of COVID-19 infection or vaccine, adverse drug effect of antitubercular medicines or a paradoxical reaction during the tuberculosis treatment. The patient could not survive beyond two months of diagnosis because of rapidly declining renal functions. This case highlights the importance of a meticulous clinical approach, supports two week tuberculosis medicines trial and an early and careful dealing of non responders during tuberculosis treatment especially in patients whose diagnosis is not microbiologically confirmed.

Three Diseases Mediated by Different Immunopathologic Mechanisms-ANCA-Associated Vasculitis, Anti-Glomerular Basement Membrane Disease, and Immune Complex-Mediated Glomerulonephritis-A Common Clinical and Histopathologic Picture: Rapidly Progressive Crescentic Glomerulonephritis.

Immune mechanisms play an important role in the pathogenesis of glomerulonephritis (GN), with autoimmunity being the main underlying pathogenetic process of both primary and secondary GN. We present three autoimmune diseases mediated by different autoimmune mechanisms: glomerulonephritis in vasculitis mediated by anti-neutrophil cytoplasmic antibodies (ANCAs), glomerulonephritis mediated by anti-glomerular basement membrane antibodies (anti-GBM antibodies), and immune complex-mediated glomerulonephritis. Some of these diseases represent a common clinical and histopathologic scenario, namely rapidly progressive crescentic glomerulonephritis. This is a severe illness requiring complex therapy, with the main role being played by therapy aimed at targeting immune mechanisms. In the absence of immune therapy, the crescents, the characteristic histopathologic lesions of this common presentation, progress toward fibrosis, which is accompanied by end-stage renal disease (ESRD). The fact that three diseases mediated by different immunopathologic mechanisms have a common clinical and histopathologic picture reveals the complexity of the relationship between immunopathologic mechanisms and their clinical expression. Whereas most glomerular diseases progress by a slow process of sclerosis and fibrosis, the glomerular diseases accompanied by glomerular crescent formation can progress, if untreated, in a couple of months into whole-nephron glomerulosclerosis and fibrosis. The outcome of different immune processes in a common clinical and histopathologic phenotype reveals the complexity of the relationship of the kidney with the immune system. The aim of this review is to present different immune processes that lead to a common clinical and histopathologic phenotype, such as rapidly progressive crescentic glomerulonephritis.

A Case Report Study at the Miangul Abdul Haq Jahanzeb Kidney Hospital in Swat Found Glomerular Basement Membrane Antibody Disease with Normal Renal Function.

Background: Anti-glomerular basement membrane (GBM) antibody disease is a rare autoimmune condition causing rapidly progressive glomerulonephritis, typically affecting adults. We present an unusual case of anti-GBM nephritis in a 7-year-old child, initially identified through a routine school urine screening. This young patient displayed no overt signs of renal impairment but testing revealed the atypical presence of GBM antibodies.. Objective: The purpose of this case report is to draw attention to the uncommon occurrence of anti-GBM disease in pediatric populations presenting with normal renal function. Diagnosis and management in such cases poses challenges given our understanding of anti-GBM nephritis derives mainly from adult patients. This anomaly prompts consideration of alternate screening and treatment approaches for younger patients who may manifest the disease atypically compared to older populations. Study design: A Case Report Study. Place and duration of study: department of nephrology at the MiangulAbdul Haq Jahanzeb Kidney Hospital From January 2021 to July 2021 Methods: This Case Report study was conducted in the department of nephrology at the MiangulAbdul Haq Jahanzeb Kidney Hospital From January 2021 to July 2021 after ethical clearance for hospital administration of this study. Results: (anti-GBM) illness in infants with intact renal function is uncommon. For this reason, professionals must carefully pick an appropriate therapy for youngsters since the prognosis is grim. Conclusion: Figures 1 to 3 show that things are true of (anti-GBM) illness. (anti-GBM) infection was suspected eventhough her kidneys were in good shape. A VUR might have caused this with a bladder issue as a secondary conditionsource. As an (anti-GBM) medication, DFPP works well for those with normal renal function. Keywords: Anti-GBM, Pediatrics, Normal renal function, School urine screening programmed, case report

Significance of autoantibodies in diagnostics of systemic vasculitis

Systemic vasculitis is a heterogeneous group of disorders characterized by inflammation and necrosis in the vessel wall. Patients usually present a quite broad spectrum of manifestations which vary in terms of vessels’ size affected, organs involvement, and the extent of inflammatory process as well as an immunological diversity, including autoantibodies profile. Though, the diagnosis is based on clinical features, tissue biopsy, imaging investigations, and serologic tests. The main autoantibodies, important not only in the diagnosis but also in monitoring and prognosis of systemic vasculitides, are anti-neutrophil cytoplasmic antibodies (ANCA), anti-glomerular basement membrane antibodies (anti-GBM), anti-complement component C1q antibodies (anti-C1q), and cryoglobulins. Although other autoantibodies have been analyzed, their clinical utility still needs further investigation. The current work aimed to review the clinical associations of main autoantibodies in systemic vasculitis.

An unusual blend; IgA nephropathy and anti GBM disease

Anti-glomerular basement membrane (anti-GBM) disease is a rare illness with a wide spectrum of clinical manifestations. The typical presentation (90% of cases) of anti-GBM is with a rapidly progressive glomerulonephritis (RPGN) in conjunction with pulmonary disease in 25-60% of cases. In its atypical form – seen in 10% of cases, anti GBM disease takes on a chronic form, presenting with long standing renal dysfunction, proteinuria and better renal prognosis when compared to the typical form of the disease. The known associations of anti-GBM disease are with anti-neutrophil cytoplasmic antibody (ANCA)vasculitis and membranous nephropathy. In this case report, a young lady with atypical anti-GBM disease is described with a most unusual association with IgA nephropathy. This association is rare and only described in few case reports worldwide. The possible pathogenesis, clinical features, treatment and outcome of this disease are also elucidated.

#6541 GLOMERULONEPHRITIS DIAGNOSIS BY MACHINE LEARNING ON PERIODIC ACID-SCHIFF (PAS) WHOLE SLIDE IMAGES

Abstract Background and Aims Machine learning (ML) holds great promise for improving diagnostics, prognostication and theranostics in nephropathology. So far, applications have not gone much further than segmentation of tissue compartments on whole slide images (WSIs) of paraffin sections. As a proof-of-concept study, we describe the development of a diagnostic classifier for glomerulephritis based on expert-annotated or automatically segmented glomerular transections from periodic-acid Schiff (PAS) paraffin sections only. Method A total of n = 350 biopsies from 5 institutions with 12 classes of glomerulonephritis IgA nephropathy (IgAN), membranous nephropathy (Membranous), anti-glomerular basement membrane antibody GN (ABMGN), infection-associated GN (IAGN), ANCA-associated GN (ANCA-GN), idiopathic membranoproliferative GN (MPGN), SLE GN class IV (SLE-GN-IV), cryglobulinemic GN (CryoGN), C3 GN (C3-GN), dense deposit disease (DDD), fibrillary GN (FibrillaryGN) and proliferative GN with monoclonal immunoglobulin deposits (PGNMID) were included in the study with their respective PAS sections. Glomerular transections were expert-annotated by a nephropathologist and automatically segmented with our own transformer-based segmentation model trained on 100 biopsies with thrombotic microangiopathies and a range of vascular, vasculitic and glomerular diseases closely resembling/mimicking thrombotic microangiopathies. For classification, we divided the cohort into 5 folds for internal cross-validation, performed sample size augmentation with various methods (including shifts in resolution/scale, AutoAugment and others) and trained our proprietary self-attention-based MILx architecture on an EfficientNet backbone with selection of glomerular crop batches by soft Markov chain Monte Carlo sampling in a semi-supervised fashion, with diagnostic class labels for each biopsy. We compared the performance of our proprietary architecture on both expert-annotated and automatically segmented glomerular crops with a recently published benchmark architecture (CLAM) for multiple-instance learning in histopathology. Results Automatic glomerular segmentation performance was excellent with mean AUC and sensitivity (mean average recall) over all classes at 0.904, with near perfect mean average specificity (0.994), as expected best for Membranous, worst for ABMGN. Classification performance of MILx with expert-annotated glomerular crops as inputs had a mean balanced accuracy of 0.84, with AUC metrics in descending order of 0.97 for Membranous, 0.89 for ABMGN, 0.88 for IgAN, 0.86 for Fibrillary, 0.83 for MPGN, 0.80 for ANCA-GN, 0.79 for DDD, 0.78 for PGNMID, 0.75 for IAGN, 0.73 for SLE-GN-IV and CryoGN, 0.67 for C3-GN. Performance with MILx was similar for automatically segmented glomerular crops as input. On this dataset, MILx outperformed CLAM with both entire WSIs as well as expert-annotated glomerular crops as inputs (mean balanced accuracy of 0.72) by a significant margin. Conclusion This proof-of-concept-study indicates that nephropathology-specific architectures like our MILx can be trained for complex tasks on relatively small biopsy cohorts. We should be able to deliver an end-to-end-pipeline for this diagnostic and other tasks based on training sets with case-labels provided by trusted institutions with only minimal expert labeling or annotation required. PAC and HQ contributed equally to this work.

#2968 PROGNOSIS OF CRESCENTIC GLOMERULONEPHRITIS IN ADULTS

Abstract Background and Aims Crescentic glomerulonephritis (C-GN) is characterized by severe glomerular inflammation and injury that leads to crescent formation, rapid loss of kidney function and severe prognosis in absence of prompt immunosuppressive therapy. Depending on the histological findings, there are three main types of C-GN: anti-glomerular basement membrane antibody GN (anti-GBM GN), immune complex GN, and pauci-immune GN. This study aims to assess whether the kidney and vital outcome are different among the three histologic types of crescentic GN. Method This unicentric, retrospective study included seventy-six subjects [50% males, 55 (95%CI 52 to 60) years; eGFR 9.6 (95%CI 7.8-13.7) mL/min and proteinuria 1.9 (95%CI 1.5 to 2.6) g/g] that had undergone a kidney biopsy between 1st January 2008 and 31st December 2017 and had a histologic diagnosis of crescentic glomerulonephritis (crescent formation in more than 50% of the glomeruli). The subjects were followed for a mean of 47.6 (95%CI 33.5 to 61.6) months. Primary endpoints were the need of renal replacement therapy initiation (RRT) and all cause death. Kaplan-Meier method was used to evaluate kidney and patients’ survival and variables related to kidney and vital outcome were evaluated by multivariate Cox proportional hazard modelling. Patients were stratified in three groups according to the type of C-GN: pauci-immune GN (n=58 pts.), anti-GBM GN (n=9 pts.) and immune-complex GN (n=9 pts.). Results No demographic differences were found among the three groups. Except for a higher frequency of solid neoplasia in immune-complex GN group (2.7% vs 1.3% in pauci-immune GN vs. 0% in anti-GBM GN; P = .001), no other differences regarding the clinical or laboratory data were identified. Immunosuppressive treatment was very frequent, in more than 80% of subjects, regardless of the group, corticotherapy and cyclophosphamide being the most common immunosuppressive agents. During the follow-up period, 54% of subjects needed RRT and 19.2% died. The frequency of RRT initiation or death was not different among the three groups (P = .9 and P = .4). The univariate time-dependent analysis showed similar survival times among the analysed groups (log rank =0.9) (Figure 1). In the multivariate analysis, the only independent predictor of RRT was lower baseline eGFR (OR 0.49 (95%CI 0.31 to 0.78), P = .03). Time to death did not differ among groups (log rank P = .4) (Figure 2). The only independent predictor of death was higher Charlson comorbidity score (OR 56.8 (95%CI 6.3 to 512), p<0.001) in the Cox analysis. Conclusion In this cohort of subjects with crescentic glomerulonephritis, although limited by the low number of subjects, the kidney and vital prognosis seem to be similar indifferent of the histologic type of crescentic glomerulonephritis.

#5034 ANCA ASSOCIATED VASCULITIS AFTER COVID-19

Abstract Background and Aims ANCA associated vasculitis (AAV) is a group of systemic autoimmune diseases characterized by inflammation of small and medium sized vessels. The three main types of AAV are granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Similar pathways are involved mechanisms of disease involving COVID-19 and ANCA-associated vasculitis. For instance, neutrophil extracellular traps (NETs) are induced in both entities. Method We describe 3 cases reports of patients with ANCA associated vasculitis after COVID19. Results Case 1: A 46-year-old female patient was hospitalized in intensive care unit for COVID19 pneumonia. She has fever, cough and dyspnea. A few days before, the SARS-CoV-2 polymerase chain reaction(PCR) was positive on nasopharyngeal swab. She received high flu nasal canula. She presented a pneumo-renal syndrome with intra-alveolar hemorrhage and acute kidney injury. Chest scanner shows lesions on bilateral lung parenchyma, and an acute kidney injury (AKI) on admission. Urinalysis revealed an active sediment with dysmorphic erythrocytes and signifcant proteinuria. Renal function gradually deteriorated. So intermittent hemodialysis treatment was initiated. Serological evaluation showed negative antinuclear antibody, and anti-dsDNA, normal serum complements, and an elevated MPO. In kidney biopsy, pauci-immune necrotizing GN with cellular crescents was detected. The patient received pulse dose corticosteroids and subsequently, she was transitioned to oral prednisone. She underwent 2 sessions of plasmapheresis, which were stopped in the absence of confirmation of pulmonary involvement. She received cyclophosphamide during the hospitalization. While hematuria and proteinuria were persistant in the most recent urinalysis, the sCr level decreased to 159 µmol/L. In addition, she developed adrenal insufficiency after stopping corticosteroid therapy, requiring her to be put on Cortef. Case 2: A 63-year-old female patient with past medical history of hypertension, was hospitalized in intensive care unit for dyspnea and hemoptysis. A few months before, the SARS-CoV-2 polymerase chain reaction(PCR) was positive on nasopharyngeal swab. She received high flu nasal canula (HFNC). At this moment, she had acute kidney injury with a sCr level of 165µmol/L that was not explored. Currently she presented a pneumo-renal syndrome with a rapidly progressive glomerulonephritis and intra-alveolar hemorrhage. Renal function gradually deteriorated and peak sCr level of 308µmol/L. Chest scanner shows ground glass lesions of bilateral lung parenchyma, and hemoglobin at 4.9 g/dL. Urinalysis revealed an active sediment with dysmorphic erythrocytes and signifcant proteinuria. So intermittent hemodialysis treatment was initiated. The patient received pulse dose corticosteroids and subsequently, she was transitioned to oral prednisone. She received cyclophosphamide during the hospitalization. Serological evaluation showed negative antinuclear antibody, and anti-dsDNA, normal serum complements, and an elevated MPO. She underwent 6 sessions of plasmapheresis, for intra-alveolar hemorrhage. There was an improvement in respiratory and renal function Case 3: 57 years old, with a history of functional colopathy, covid infection 1 month before her hospitalization in nephrology department for kidney injury. Currently she presented a pneumo-renal syndrome with a rapidly progressive glomerulonephritis and intra-alveolar hemorrhage. Urinalysis revealed an active sediment with dysmorphic erythrocytes and signifcant proteinuria. Serological evaluation showed negative antinuclear antibody, and anti-dsDNA, normal serum complements, an elevated MPO and positive anti GBM. She was treated with plasmapheresis and cyclophosphamide. Conclusion SARS-CoV-2 infection can be a 'trigger factor' for vasculitis. ANCA-associated vasculitis should be kept in mind in patients who develop acute kidney injury after COVID-19.

An Atypical Case of Anti GBM Disease

Anti GBM disease is a very rare type of small vessel vasculitis. The incidence is around less than 1 per million per year .This disease is also known as “Good Pasteur Disease”. Usually it presents with rapidly progressive glomerulonephritis with or without lung haemorrhage. The pathognomonic hallmark of the disease is strong linear IgG deposition along the GBM along with positive anti GBM antibody. But when the circulating antibody is absent in the blood, with mild renal impairment it is termed as atypical anti GBM disease. Recently we have found a 26 years old gentleman who presented with leg swelling for 1.5 months along with decreased urine output. He was non diabetic, normotensive, there was no history of joint pain, rash, no offending medication intake, or coughing out of blood. His urine R/E report showed Alb+++, RBC-plenty. After admission his serum creatinine was increasing rapidly. We have done renal biopsy and started treatment with I/V methylprednisolone followed by oral steroid. He had nephrotic range proteinuria. His auto antibody profile and HBsAg, Anti HCV was negative. We have done renal biopsy and it showed crescentic GN with strong linear deposition of IgG. His anti GBM Ab was negative. Thus we labelled the case as atypical anti GBM disease. Now patient is on RRT and we started therapeutic plasma exchange. J Medicine 2023; Vol. 34, No. 2(1) Supplement: 220

Goodpasture’s Syndrome in Children: About a Case Report

Pulmonary-renal syndrome is a medical condition that encompasses a range of clinical symptoms that can appear in various diseases. It is identified by the occurrence of both pulmonary hemorrhage and glomerulonephritis. While this syndrome is rare in children, it can pose a medical emergency if it does occur. Goodpasture's syndrome (GPS) is one of the infrequent causes of pulmonary-renal syndrome in childhood. This article presents a case study detailing the diagnosis of Goodpasture's Syndrome in a 5-year-old pediatric patient with a medical history of nephrotic syndrome, glomerulonephritis at end-stage renal failure, and the presence of anti-glomerular basement membrane (anti-GBM) antibodies. The patient was admitted to the emergency department due to hemoptysis, a hallmark symptom of this syndrome.

Glomerulonefritis agudas y rápidamente progresivas, glomerulonefritis proliferativa endocapilar y glomerulonefritis proliferativa extracapilar

Acute (post-infectious) glomerulonephritis presents rapidly with hematuria (microscopic or causes), proteinuria, a decrease in glomerular filtration rate, and sodium and water retention that usually cause an increase in blood pressure and edema. In addition, various types of chronic glomerulonephritis may present as acute nephrotic syndrome and can be clinically indistinguishable from the onset of acute abnormalities. Rapidly progressive glomerulonephritis (RPGN) represents a clinical-pathological syndrome characterized by a rapid decline in renal function (weeks to months); proteinuria generally in a subnephrotic range; and the presence of fibrous, cellular crescents in the glomerular area. Its causes can be primary or secondary. Its classification depends on clinical, serological, and histological findings; they are divided into 3 types: 1, associated with anti-glomerular basement membrane antibodies; 2, associated with immune complexes; 3 pauci-immune (ANCA-associated), or 4, a combination of types 1 and 3. Diagnosis and treatment must be early. High-dose immunosuppressants and, sometimes, plasmapheresis can be used for the purpose of restoring renal function and avoiding rapid progression to advanced or end-stage chronic kidney disease. In cases with very high clinical suspicion, performing a renal biopsy must not delay starting immunosuppressive therapy.