Crescentic glomerulonephritis due to linear IgA anti-glomerular basement membrane disease: report of a rare case.

Anti-glomerular basement membrane (GBM) disease is a rare and severe vasculitis that affects the glomerular and pulmonary capillaries and has an incidence of less than 2 cases per million individuals per year. Anti-GBM disease is mediated by autoantibodies against the α3 chain of type IV collagen. In the majority of cases, the autoantibodies are of the immunoglobulin G (IgG) class, with rare cases being mediated by immunoglobulin M (IgM) or immunoglobulin A (IgA); there are less than 15 IgA-mediated cases reported in the literature worldwide. The classic form of this disease manifests with rapidly progressive glomerulonephritis (RPGN), with or without pulmonary hemorrhage, and the diagnosis consists of identifying high titers of autoantibodies in the serum and/or deposited in the tissues. IgA antibodies are not identified in routine immunoassay tests, and renal biopsy with immunofluorescence is essential for diagnosis. We present a case of RPGN due to anti-GBM disease with linear IgA deposition, whose diagnosis was made exclusively by renal biopsy and with an unfavorable prognosis.

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.

Anti-GBM disease in pregnancy.

We present the case of a pregnant woman in her 20s who presented in her second trimester with severe pulmonary haemorrhage and dialysis-dependent acute kidney failure due to antiglomerular basement membrane (GBM) disease. Responding to therapy, she recovered kidney function and delivered a baby. During her pregnancy, she developed cytomegalovirus viraemia, gestational diabetes and pre-eclampsia. Here, we report the first combined use of cyclophosphamide, rituximab and intensified plasma exchange in anti-GBM disease in pregnancy, allowing minimal exposure to cytotoxic medication, resulting in live birth and dialysis independence.

Epidemiology, clinical features, risk factors, and outcomes in anti-glomerular basement membrane disease: A systematic review and meta-analysis.

Anti-glomerular basement membrane (GBM) disease is a small-vessel vasculitis that represents the most aggressive form of autoimmune glomerulonephritis. The study aimed to investigate the prevalence, clinical characteristics, risk factors, and outcomes of anti-GBM disease through a systematic review and meta-analysis involving 47 studies with 2830 patients. The overall incidence of anti-GBM disease ranged from 0.60 to 1.79 per million population per annum. In rapidly progressive glomerulonephritis and crescentic glomerulonephritis, the pooled incidence rates were 8.0% and 12.8%, respectively. The pooled prevalence rates of anti-GBM antibodies, antineutrophil cytoplasmic antibodies (ANCA), and lung hemorrhage were 88.8%, 27.4%, and 32.6%, respectively. Patients with combined ANCA positivity demonstrated a prognosis comparable to those patients with only anti-GBM antibodies, though with differing clinical features. The pooled one-year patient and kidney survival rates were 76.2% and 30.2%, respectively. Kidney function on diagnosis and normal glomeruli percentage were identified as strong prognostic factors. This study represents the first comprehensive meta-analysis on anti-GBM disease, providing insights into its management. However, caution is warranted in interpreting some results due to the observational nature of the included studies and high heterogeneity.

Coexistence of anti-glomerular basement membrane disease and IgA nephropathy: an illustrative case and comprehensive literature review.

Anti-glomerular basement membrane (GBM) disease is a rare autoimmune condition characterized by the presence of positive anti-GBM autoantibodies, linear deposition of immunoglobulin G (IgG) along the GBM and severe kidney injury. In a limited number of cases, the association of anti-GBM disease with other glomerulonephritis has been reported. Herein, we present the case of a 66-year-old female patient with progressive worsen kidney function and decreased urine output. A renal biopsy revealed crescent glomerulonephritis with lineal IgG deposition along the GBM and mesangial IgA deposition, which supported the diagnosis of concurrent anti-GBM disease and IgA nephropathy (IgAN). In an extensive literature review, we identified a total of thirty-nine patients were reported anti-GBM disease combined with IgAN. The clinical characteristics of these patients demonstrate that the anti-GBM disease combined with IgAN tends to be milder with a more indolent course and a better prognosis than the classic anti-GBM disease, and its potential pathogenesis deserves to be further explored.

Goodpasture syndrome: a rare case presenting with recurrent haemoptysis.

Goodpasture syndrome is a rare autoimmune disease which affects young adults with a male preponderance and can be triggered at any point in life with a classical clinical triad of rapidly progressive glomerulonephritis, diffuse pulmonary haemorrhage and circulating anti-glomerular basement membrane antibody (anti-GBM antibody). Here we are presenting a case of a young man with hypertension in his early 20s who presented with fatigue, recurrent haemoptysis, breathlessness and decreased urine output without features of infection. He was diagnosed at an early stage of the disease with the help of clinical, serological and radiological findings. An early diagnosis with effective treatment using plasma exchange, intravenous high-dose methylprednisolone, and cyclophosphamide showed a rapid improvement in the patient's condition with an immediate decrease in anti-GBM titres and proteinuria.

Atypical Anti-Glomerular Basement Membrane Nephritis: A Case Series From the French Nephropathology Group.

RATIONALE & OBJECTIVE: Atypical anti-glomerular basement membrane (GBM) nephritis is characterized by a bright linear immunoglobulin staining along the GBM by immunofluorescence without a diffuse crescentic glomerulonephritis nor serum anti-GBM antibodies by conventional enzyme-linked immunosorbent assay (ELISA). We characterized a series of patients with atypical anti-GBM disease. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Patients identified by the French Nephropathology Group as having atypical anti-GBM nephritis between 2003 and 2022. FINDINGS: Among 38 potential cases, 25 were included, of whom 14 (56%) were female and 23 (92%) had hematuria. The median serum creatinine at diagnosis was 150 (IQR, 102-203) µmol/L and median urine protein-creatinine ratio (UPCR) was 2.4 (IQR, 1.3-5.2) g/g. Nine patients (36%) had endocapillary proliferative glomerulonephritis (GN), 4 (16%) had mesangial proliferative GN, 4 (16%) had membranoproliferative GN, 2 (8%) had pure and focal crescentic GN, 1 (4%) had focal segmental glomerulosclerosis, and 5 had glomeruli that were unremarkable on histopathology. Nine patients (36%) had crescents, involving a median of 9% of glomeruli. Bright linear staining for IgG was seen in 22 cases (88%) and for IgA in 3 cases (12%). The 9 patients (38%) who had a monotypic staining pattern tended to be older with less proteinuria and rarely had crescents. Kidney survival rate at 1 year was 83% and did not appear to be associated with the light chain restriction. LIMITATIONS: Retrospective case series with a limited number of biopsies including electron microscopy. CONCLUSIONS: Compared with typical anti-GBM disease, atypical anti-GBM nephritis frequently presents with an endocapillary or mesangial proliferative glomerulonephritis pattern and appears to have a slower disease progression. Further studies are needed to fully characterize its pathophysiology and associated clinical outcomes. PLAIN-LANGUAGE SUMMARY: Atypical anti-glomerular basement membrane (GBM) nephritis is characterized histologically by bright linear immunoglobulin staining along the GBM without diffuse crescentic glomerulonephritis or circulating anti-GBM antibodies. We report a case series of 25 atypical cases of anti-GBM nephritis in collaboration with the French Nephropathology Group. Compared with typical anti-GBM disease, we observed a slower disease progression. Patients frequently presented with heavy proteinuria and commonly had evidence of endocapillary or mesangial proliferative glomerulonephritis. About half of the patients displayed a monotypic immune staining pattern; they tended to be older, with less proteinuria, and commonly without glomerular crescents in biopsy specimens. No concomitant circulating monoclonal gammopathy was detected. Further studies are needed to fully characterize its pathophysiology and associated clinical outcomes.

An Unusual Case of Anti-Glomerular Basement Membrane Disease and Phospholipase A2 Receptor-Associated Membranous Nephropathy After Exposure to Hydrocarbons.

We present a rare case of a patient with toluene exposure manifesting as anti-glomerular basement membrane (GBM) disease on a background of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy. A 23-year-old man presented to the emergency department with hypertension, headache, hemoptysis, anemia, acute kidney injury, glomerular hematuria, and proteinuria. He endorsed repeated exposure to toluene-containing products while repairing dirt bikes. Serologies were positive for anti-GBM antibodies. Kidney biopsy showed crescentic glomerulonephritis with linear immunoglobulin G and granular PLA2R staining by immunofluorescence. He was initially treated with high-dose steroids, plasmapheresis, and hemodialysis for pulmonary-renal syndrome followed by oral cyclophosphamide and prednisone, which were discontinued after 3 months when follow-up biopsies confirmed little chance for renal recovery. He remained on dialysis 1 year later. This case exhibits a unique presentation of anti-GBM syndrome and underlying membranous nephropathy following repeated hydrocarbon exposure. Inhaled toxins promote recurrent localized inflammation, unmasking previously hidden epitopes. Early diagnosis and appropriate use of immunosuppressive and extracorporeal therapies are necessary to prevent morbidity and to improve survival in this rare condition.

Antiglomerular basement membrane antibody type rapidly progressive glomerulonephritis with seizures: Two cases and literature review.

BACKGROUND: Rapidly progressive glomerulonephritis (RPGN) is clinically manifestations as a rapidly progressive renal failure and pathologically as crescentic and necrotizing lesions with infiltration of inflammatory cells in the glomeruli. Uremic encephalopathy (UE) usually develops in patients who are suffering from acute or chronic renal failure. OBJECTIVE: The purpose of this article is to provide reference for clinical diagnosis and treatment of renal disease complicated with seizures. Patients Two cases of anti-glomerular basement membrane type rapidly progressive glomerulonephritis complicated with seizures were reported. MATERIALS & METHODS: In case 1, a 40-year-old woman was hospitalized for the treatment of nausea, anorexia, and fever. On admission, she presented with elevated serum inflammatory indicators, moderate anemia, and advanced acute kidney injury requiring hemodialysis. Her anti-glomerular basement membrane (GBM) antibody in serum and renal tissues was found to be extremely high. She was finally diagnosed with anti-GBM disease. She was treated with a combination of corticosteroid pulse therapy, oral cyclophosphamide and prednisolone, and plasma exchange, while continued to require maintenance hemodialysis for end-stage kidney disease. During treatment, she suddenly suffered blindness, seizure, and consciousness disturbance. She was diagnosed as posterior reversible leukoencephalopathy syndrome by magnetic resonance imaging (MRI). The posterior reversible leukoencephalopathy syndrome subsided quickly after control of her hypertension and reinforcement of immunosuppressive treatment. In case 2, the patient also developed epileptic symptoms on the basis of GBM disease, and was given treatment similar to that of Case 1, so that the epileptic symptoms were controlled. RESULT: Reversible posterior leukoencephalopathy syndrome, especially when accompanied by cerebral hemorrhage, may lead to irreversible and lethal neurological abnormalities, and nephrologists should, therefore, be aware of the potential risk of reversible posterior leukoencephalopathy syndrome in patients with anti-GBM disease. We can discuss the current two cases in the light of the previous literature.

Atypical form of Goodpasture's disease.

Goodpasture's disease and anti-glomerular basement membrane nephritis (anti-GBM nephritis) are rare autoimmune small vessel vasculitis predominantly affecting young men. Goodpasture's disease plays an important part in differential diagnosis of pulmonary - renal syndrome. The evidence of circulating autoantibodies, a typical histological appearance of the kidney biopsy with finding of the crescent glomerulonephritis and clinical presentation of nephritic syndrome play an important role in diagnosis. Our case report describes a case of a young male with anti-GBM nephritis that presents as rapidly progressive glomerulonephritis (RPGN) with progression to dialysis-dependent renal failure. The atypical sign of the case was development of nephrotic syndrome with volume-dependent hypertension. The case was complicated by heparin-induced thrombocytopenia. During combined immunosuppressive therapy with plasmapheresis, the condition of the patient has stabilized. However, renal function did not recover. This previously fatal disease has nowadays a very good survival rate because of immunosuppresion therapy, plasmapheresis and hemodialysis.

Anti-Glomerular Basement Membrane Disease in a 10-year-old Child: A Case Report.

Anti-glomerular basement membrane disease is an extremely uncommon entity in children. It has an incidence of 0.5 to 1 per million per year in adults and is even more uncommon in children. It occurs due to autoantibody against glomerular basement membrane collagen and is characterized by rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. As the literature on anti-glomerular basement membrane disease is limited from our part of the world, it is important to consider it as the rare cause of rapidly progressive glomerulonephritis as early intervention improves prognosis. We report a case of a 10-year-old male who initially presented with glomerulonephritis and later was diagnosed with anti-glomerular basement membrane disease. Keywords: basement membrane; case reports; glomerulonephritis; kidney.

[Anti-MBG crescentic glomerulonephritis with negative immunofluorescence: case report and literature review].

Anti-glomerular basement membrane (anti-GBM) antibody disease is a rapidly progressive glomerulonephritis characterized by (i) positivity to anti-GBM in serum reacting with a specific antigen present in type IV collagen at both the glomerular and alveolar levels (ii) presence of crescent on light microscopy and positivity to linear deposits of IgG and C3 on immunofluorescence. In the classic variant, the clinic is that of a nephro-pneumological syndrome but there are variants. Rarely, the glomerular damage is pauci-immune. We describe a case of a variant in which there is anti-MBG positivity in serum but negative immunofluorescence and offer a review of the literature and potential treatments.

[Anti-glomerular basement membrane disease]. / Maladie des anticorps anti-membrane basale glomérulaire.

Anti-glomerular basement membrane disease is a rare disease. In its classical presentation it associates rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage, linked to the presence of antibodies targeting type IV collagen in the glomerular and alveolar basal membrane. Anti-GBM disease warrants prompt medical management to limit permanent kidney damage and mortality. Treatment includes plasma exchanges to quickly remove pathogenic antibodies and immunosuppressants to stop their production. This article reviews the pathogenesis and current treatments.

La maladie des anticorps anti-membrane basale glomérulaire (anti-MBG) est une entité rare. Dans sa présentation classique, elle associe une glomérulonéphrite rapidement progressive et une hémorragie alvéolaire diffuse liée à des anticorps dirigés contre le collagène de type IV des membranes basales glomérulaire et alvéolaire. Les pronostics rénal et vital sont engagés. Le traitement doit être prompt et comprend des plasmaphérèses visant à éliminer les anticorps pathogéniques ainsi qu'une immunosuppression destinée à supprimer leur production. Cet article passe en revue la pathogénie et les traitements actuels.

Goodpasture syndrome and anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (anti-GBM) disease is a rare life-threatening small vessel vasculitis that typically affects the capillaries of kidneys and lungs, with most of patients developing rapidly progressive crescentic glomerulonephritis, and 40%-60% concomitant alveolar haemorrhage. It is caused by the deposition in alveolar and glomerular basement membrane of circulating autoantibodies directed against antigens intrinsic to the basement membrane. The exact mechanism that induces the formation of autoantibodies is unknown, but probably environmental factors, infections or direct damage to kidneys and lungs may trigger the autoimmune response in genetically susceptible individuals. Initial therapy includes corticosteroids and cyclophosphamide to prevent autoantibodies production, and plasmapheresis to remove the circulating autoantibodies. Good renal outcomes may be achieved by a prompt treatment initiation. However, when patients present with severe renal failure requiring dialysis or with a high proportion of glomerular crescents at biopsy, renal outcomes are bad. Relapses are rare and when renal involvement is present, the suspect of concomitant diseases, such as ANCA-associated vasculitis and membranous nephropathy, should be raised. Imlifidase is showing promising results, which if confirmed will cause a paradigm shift in the treatment of this disease.

Case Report: Bilateral Lung Transplantation for Rapidly Progressive Undifferentiated Interstitial Lung Disease-A Cautionary Tale.

Interstitial lung disease is fast becoming one of the most common indications for lung transplantation (LTx); however, LTx for Goodpasture's syndrome with pulmonary involvement has not been previously described in the literature. In this report, we outline the case of a young male with undifferentiated rapidly progressive interstitial lung disease who ultimately received a bilateral sequential LTx after deterioration requiring extracorporeal membrane oxygenation. The original disease soon recurred in the graft, and unfortunately, the patient did not survive. The diagnosis of Goodpasture's syndrome was made postmortem and was not clearly evident on examination of the native explanted tissue, nor was there an elevated titer of antiglomerular basement membrane antibodies during his initial work-up. We hypothesize that the donor and recipient's HLA profile made him more susceptible to aggressive disease. In hindsight, active Goodpasture's disease would have been a contraindication to proceed to transplantation. This case is a cautionary reminder of the high stakes of performing LTx without a certain diagnosis.

An atypical anti-GBM disease complicated by idiopathic nodular glomerulosclerosis: Case report.

Both atypical anti-glomerular basement membrane (anti-GBM) disease and idiopathic nodular glomerulosclerosis are rare diseases. We report a case of a 53-year-old non-diabetic male who presented with leg edema, nephritic range proteinuria, microscopic hematuria, and decreased renal function. The renal biopsy demonstrated membranoproliferative glomerulonephritis (MPGN) pattern of glomerular injury with focal crescent and segmental nodular glomerulosclerosis. The immunofluorescence studies showed intense linear IgG (IgG1 and IgG4) deposits along the GBM but negative serology. Electron microscopy demonstrated GBM thickening and fibrillar deposition. The presence of MPGN with crescents and the linear IgG along the GBM were consistent with a diagnosis of atypical ant-GBM disease. Superimposed nodular glomerulosclerosis was considered to be idiopathic by excluding other glomerular diseases characterized by fibrillar deposition and nodular glomerulosclerosis. Both diseases were found to have a strong causative association with patient's history of long-term heavy smoking. This unusual case with combination of atypical anti-GBM disease and idiopathic nodular glomerulosclerosis, has brought great challenge for the diagnosis and also made the clinical course highly complicated. This nodular glomerulosclerosis with anti-GBM-like glomerulonephritis may represent a distinct pattern of kidney injury observed in heavy smokers.

Anti-glomerular basement membrane disease developing 3 years after the development of Sweet syndrome and 1 year after the development of anti-neutrophil cytoplasmic antibody-associated vasculitis: a case report.

A 73-year-old Japanese woman, with a history of Sweet syndrome diagnosed 3 years earlier and anti-myeloperoxidase (MPO) antibody anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis diagnosed 1 year earlier, presented with an episode of rapidly progressive glomerulonephritis (RPGN) with anti-glomerular basement membrane (GBM) disease. At the time of diagnosis of the ANCA-associated vasculitis 1 year earlier, serological testing yielded a negative result for anti-GBM antibody. However, at the present visit, serology for anti-MPO antibody was negative, while that for anti-GBM antibody was positive. This is the first report of anti-GBM disease developing sequentially after Sweet syndrome and ANCA-associated vasculitis. This case may provide clues to the potential immunological links among these three distinct conditions.