Anti-glomerular basement membrane (GBM) disease is a rare autoimmune disease characterized by injury to small blood vessels in the kidneys and/or lungs. IgA nephropathy is the most common primary glomerular disease diagnosed in China. However, the co-occurrence of anti-GBM illness and IgA nephropathy has been infrequently documented in the literature. At present, its mechanism is unknown, the treatment approach is unclear, and the prognosis remains poor. Herein, we report a case of anti-GBM disease complicated with IgA nephropathy, in which renal function returned to normal state following treatment with a combination of prednisone and cyclophosphamide. This case suggests that in patients with anti-GBM disease and IgA nephropathy, the combination of glucocorticoids and cyclophosphamide may serve as an optimum treatment choice.

Goodpasture's syndrome (anti-glomerular basement membrane (anti-GBM) disease) is a rare, life-threatening autoimmune condition characterized by rapidly progressive glomerulonephritis and pulmonary hemorrhage. We describe a woman in her 60s with a history of breast cancer treated with lumpectomy and radiotherapy who developed hemoptysis, hematuria, acute kidney injury, and respiratory failure. She lacked traditional environmental risk factors, like cigarette smoking, hydrocarbon exposure, respiratory infections, and inhalational lung injury associated with anti-GBM disease. Diagnosis was established through positive circulating anti-GBM antibodies and a confirmatory lung biopsy demonstrating linear IgG deposition along the alveolar basement membrane. Her course was complicated by respiratory failure requiring tracheostomy, recurrent infections, anemia, and transient dialysis dependence. The patient improved following aggressive immunosuppression, plasmapheresis, and supportive care. This case highlights the diagnostic challenges of anti-GBM disease in critically ill patients, and although a causal relationship cannot be established from a single case, we evaluate how prior radiotherapy may have contributed to disease development in a susceptible individual.

Anti-glomerular basement membrane (GBM) disease is the most severe form of autoimmune glomerulonephritis following assaults on kidney and alveolar basement membranes by pathogenic anti-GBM antibodies. Typically, anti-GBM disease is characterized by rapidly progressive glomerulonephritis and an increased risk of lung hemorrhage, with kidney biopsy revealing ominous crescent formation. Although patient survival has improved with standard of care including plasma exchange and intensive immunosuppression in the recent decade, kidney survival still remains poor because of delayed recognition and tardy initiation of standard therapy. With the increasing understanding of the disease in clinical practice, several variant forms have been recognized. We here propose to group these forms into 4 categories according to their immunologic properties and clinical presentations: overlapping autoimmune syndromes (anti-GBM disease with combined antineutrophil cytoplasmic antibody, concurrent membranous nephropathy, or IgA nephropathy), immunologic distinct forms (Alport post-transplant anti-GBM disease and seronegative anti-GBM disease), clinical phenotypic variant forms (recurrent anti-GBM disease in native kidney, anti-GBM disease in elderly individuals, or with normal kidney function), and medication-associated anti-GBM disease. These patients have different features in terms of clinical manifestations, pathologic findings, or prognosis compared with patients with classical anti-GBM disease. In this review, we discuss these variant forms with emphasis on their phenotypes and underlying mechanisms. An enhanced understanding of pathophysiology of anti-GBM disease variant forms can pave the way for personalized therapies tailored to patients with different presentations of the disease.

Anti-glomerular basement membrane (anti-GBM) nephritis is a rare but highly aggressive cause of rapidly progressive glomerulonephritis (RPGN). Early recognition is essential, as delayed diagnosis leads to irreversible kidney damage and poor prognosis. We report an 8-year-old girl with anti-GBM nephritis initially misattributed to kidney involvement of IgA vasculitis (IgAV). Diagnosis was confirmed by markedly elevated anti-GBM antibodies and kidney biopsy findings. Despite plasma exchange and immunosuppressive therapy, kidney function deteriorated to kidney failure within several months. This case provides an important clinical insight for pediatric nephrologists: worsening urinary findings or kidney function during follow-up of IgAV should prompt consideration of RPGN and appropriate serological screening, as well as timely kidney biopsy, rather than being attributed solely to IgAV nephritis.

Anti-glomerular basement membrane (anti-GBM) is a rare autoimmune but life-threatening disease cause by pathogenic autoantibodies targeting a well characterized autoantigen (a-3 chain of type IV collagen) expressed in the basement membranes of the kidney and lung. Standard treatment normally includes the combination of plasma ex- change, oral cyclophosphamide and corticosteroids. Despite all therapeutic efforts, renal prognosis remains very poor in many cases. Recent studies demonstrated the pathogenic role of complement activation in renal damage of this disease. Eculizumab is a terminal complement inhibitor that binds to the human C5 complement protein, thus blocking the generation of proinflammatory C5a and C5b-9. This provides an immediate inhibition of the proinflammatory and cytotoxic sequelae of the complement system. Here, we report the successfully use of eculizumab in 2 patients with progressive anti-GBM disease.

A woman in her 20s was referred to renal clinic for investigation regarding positive anti-glomerular basement membrane (anti-GBM) antibody results. Autoimmune screening was performed to investigate an episode of fever, cough and haemoptysis which presented alongside the formation of a maculopapular rash and mild proteinuria (1+) on urine reagent dipstick.Despite repeated positive anti-GBM results obtained through BioPlex 2200 multiple antibody (multiplex) immunoassay, examination four months later was unremarkable, all signs and symptoms being resolved. Urinalysis, imaging and renal function tests demonstrated no signs of disease.False positive multiplex immunoassay results were confirmed by Phadia EliA single antibody (singleplex) fluoroenzyme immunoassay, which demonstrated anti-GBM antibody levels within normal ranges. With recent positive Epstein-Barr virus serology, unspecific proteins (heterophile antibodies) made in response remain the likely false positive cause. This case highlights the risk of heterophile antibody-induced false positives in multiplex testing, heightening the risk of misdiagnosis and unnecessary intervention.

BACKGROUND Levamisole, a widely used adulterant in illicit cocaine, has emerged as an important cause of cocaine-levamisole-associated vasculopathy (CLAV), a syndrome that can mimic primary ANCA-associated vasculitis. Typical features include neutropenia, atypical ANCA patterns, thrombotic manifestations, diffuse alveolar hemorrhage (DAH), and crescentic glomerulonephritis (GN). Dual MPO-PR3 ANCA positivity is strongly suggestive of drug-induced vasculopathy. CASE REPORT We report the case of a 30-year-old woman presenting with hemoptysis, anemia, and diffuse pulmonary infiltrates. Laboratory evaluation demonstrated hematuria, proteinuria, and dual MPO/PR3 ANCA positivity. Renal biopsy showed necrotizing crescentic GN, and urine toxicology confirmed cocaine exposure. She received pulse corticosteroids and rituximab. Three days after early discharge, she returned with massive hemoptysis and respiratory failure. Bronchoscopy confirmed DAH, and arterial blood gases demonstrated refractory hypoxemia with a PaO2/FiO2 ratio below 80 despite maximal ventilatory support. Plasmapheresis was initiated, followed by veno-venous extracorporeal membrane oxygenation (VV-ECMO) for worsening respiratory acidosis and persistent hypoxemia. Cyclophosphamide was added when her condition stabilized. Her respiratory status gradually improved, she was decannulated from ECMO, and renal function normalized. At 18 months, she remained in remission with minimal residual pulmonary abnormalities despite persistent MPO-ANCA positivity. CONCLUSIONS This case highlights CLAV as a severe vasculopathic mimic of ANCA-associated vasculitis. Early recognition, cessation of cocaine use, appropriate immunosuppression, and timely escalation to VV-ECMO when indicated are critical for survival in fulminant DAH.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV)-granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA)-as well as anti-glomerular basement membrane disease (anti-GBM disease) are systemic small-vessel vasculitides with high mortality. Diagnosis relies on serology/laboratory testing, organ screening, and exclusion of differential diagnoses. Biopsy must not delay therapy initiation in fulminant cases. In GPA and MPA, loss of T‑ and B‑cell tolerance and ANCA-mediated activation of neutrophils are pivotal. Diagnostic hallmarks include myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA. Kidney biopsy reveals pauci-immune necrotizing and extracapillary proliferative glomerulonephritis. Remission induction consists of glucocorticoids (GC) combined with rituximab (RTX) or cyclophosphamide (CYC). Maintenance therapy is preferably performed with RTX. EGPA is defined by eosinophilic tissue infiltration, often accompanied by asthma and nasal polyposis; ANCAs are present in 30-40%. Diagnostic evaluation includes blood count, inflammatory markers, immunoglobuline E (IgE), ANCA, and ENT, pulmonary, and cardiac evaluation. Nonorgan-threatening disease is treated with GC, whereas relapsing disease is managed with interleukin (IL)-5 pathway inhibitors. Organ- or life-threatening manifestations require GC plus CYC or RTX, followed by IL‑5 pathway inhibitors for maintenance therapy. Anti-GBM is driven by autoantibodies against type IV collagen and presents with a nephritic syndrome and/or alveolar hemorrhage. Within 24 h, diagnostic evaluation should include testing for anti-GBM antibodies and ANCA, thoracic imaging, exclusion of infection, and a kidney biopsy demonstrating linear IgG deposits. Treatment consists of plasmapheresis combined with GC and CYC, with RTX as an alternative. Maintenance therapy is not required unless concomitant ANCA positivity is present.