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.

Anti-glomerular basement membrane (anti-GBM) disease is a rare, life-threatening small vessel vasculitis affecting the kidneys and lungs, caused by autoantibodies against type IV collagen. Immune checkpoint inhibitors (ICIs) are an oncology treatment that block suppressive molecules on antitumour T lymphocytes, encouraging the immune system to attack cancerous cells. We report the case of a man in his 60s receiving the ICI pembrolizumab for lung adenocarcinoma, who presented with acute renal failure requiring renal replacement therapy and was diagnosed with anti-GBM disease. This case highlights potentially important mechanistic links between lung cancer, immunotherapy and anti-GBM disease development. In line with previous research, there is evidence that breakdown of self-tolerance in response to ICIs may predispose patients to the development of autoimmune disease. In patients on ICIs presenting with acute renal failure, it is important to consider anti-GBM disease as an aetiology alongside more common acute tubulointerstitial nephritis seen in immune-related adverse events of the kidney.

Seronegative anti-glomerular basement membrane (GBM) disease with pulmonary involvement is exceedingly rare. Most published cases involve patients with extensive smoking histories, and the prognosis is more favorable than classic, seropositive, anti-GBM disease. Herein, we describe the case of a 62-year-old man with a solitary kidney after right nephrectomy who presented with dyspnea, hemoptysis, and severe acute kidney injury. Kidney biopsy was delayed due to negative serologic evaluation, anchoring to a diagnosis of acute tubular necrosis (ATN), and presence of a solitary kidney; however, progressive kidney injury with microhematuria and proteinuria eventually prompted a biopsy that showed crescentic glomerulonephritis with linear GBM staining. The patient started immunosuppressive treatment and responded very well; he remains stable and off dialysis one year after the diagnosis.

The acute onset of malignant hypertension and acute kidney injury in patients with features suggestive of systemic sclerosis often raises concern for scleroderma renal crisis, a life-threatening complication requiring prompt recognition and angiotensin-converting enzyme inhibitor therapy. However, other autoimmune vasculitides, including antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and antiglomerular basement membrane (anti-GBM) disease, can present similarly but require immunosuppressive therapy. We reported a diagnostically challenging case of a 72-year-old woman with interstitial lung disease, Raynaud's phenomenon, and serologic findings of antitopoisomerase I antibody and antimyeloperoxidase (p-ANCA) antibodies. Given this clinical picture, scleroderma renal crisis was initially suspected. However, a kidney biopsy revealed pauci-immune necrotizing and crescentic glomerulonephritis with uniform crescents and without linear IgG deposition along the GBM. Given the uniformity of crescents, additional serologic testing revealed elevated anti-GBM antibody levels, posing a therapeutic dilemma regarding the presence of clinically significant anti-GBM disease in the absence of immunofluorescence confirmation. This case highlighted the critical role of early kidney biopsy in ambiguous presentations and the need for heightened awareness of overlapping autoimmune syndromes to guide timely and appropriate treatment. Systematic reporting of such overlap syndromes is essential for improving diagnostic accuracy and optimizing outcomes.

Anti-glomerular basement membrane (GBM) nephritis is an autoimmune disease which typically presents rapid progressive glomerulonephritis. A subacute course and relapse are rare. We report the case of a 23-year-old woman with no prior medical history, who was referred for proteinuria and elevated serum creatinine (Cr) level of 3.3 mg/dL. Two weeks later, upon her visit to our hospital, her creatinine level was 3.2 mg/dL. Five months prior, her Cr was 1.2 mg/dL. Urinalysis showed 2.3 g/gCre of proteinuria and microscopic hematuria. The anti-GBM antibody titer was high at 135 U/mL. Anti-neutrophil cytoplasmic antibody and anti-nuclear antibody were negative. Kidney biopsy revealed crescentic glomerulonephritis with advanced glomerular sclerosis and diffuse linear staining of IgG along the GBM. She received corticosteroids, intravenous cyclophosphamide and 7 sessions of plasma-exchanges. After three months, her Cr improved to 1.9 mg/dL and the antibody became undetectable. However, she self-discontinued prednisolone 2 months later. Three weeks after discontinuation, she presented with nausea, oliguria. Her Cr level had risen to 9.6 mg/dL and the anti-GBM antibody titer was 4.0 U/mL. A second kidney biopsy showed progression of glomerulosclerosis, endothelial injury in the arterioles characterized by fibrin deposition, and extensive tubulointerstitial damage. Despite resuming treatment, her kidney function did not recover, and she required maintenance hemodialysis. This case highlights two atypical features of anti-GBM nephritis: subacute progression over 5 months, and relapse after antibody negativity triggered by steroid discontinuation. This emphasizes the importance of adherence to immunosuppressive therapy, even after serological remission.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multisystem involvement and fluctuating activity. Among its many complications, cardiovascular disease (CVD) is a leading cause of morbidity and mortality, with up to 25% of patients affected. Cardiac manifestations, such as pericarditis, myocarditis, and accelerated atherosclerosis, are often underdiagnosed due to their subclinical presentation and lack of standardized screening protocols. This systematic review aims to synthesize current evidence on the incidence, detection, and prognostic challenges of cardiac complications in SLE patients and to identify gaps in current risk stratification and diagnostic methods. A comprehensive literature search was conducted across Ovid, CINAHL, EMBASE, and Web of Science using predefined search terms related to SLE, cardiovascular complications, disease flares, and diagnostic tools (e.g., biomarkers, cardiac MRI). English-language studies published between 2015 and 2025 involving adults (≥18 years) were included. Eligible studies focused on cardiac complications in SLE patients and reported outcomes such as incidence, diagnostic markers, or evidence of underdiagnosis. Exclusion criteria included pediatric populations, non-SLE autoimmune diseases, lack of cardiac outcome data, animal/in vitro studies, non-English papers, reviews, and editorials. Across 31 studies encompassing over 7,000 patients with SLE, cardiac symptoms were frequent, ranging from subclinical abnormalities to life-threatening complications. Case reports highlighted severe manifestations, including cardiac tamponade, myocarditis, cardiogenic shock, and myocardial infarction, often mimicking acute coronary syndromes. Observational and retrospective cohorts demonstrated high rates of pericardial effusion (up to 25%), pulmonary hypertension (15-42%), valvular disease (15-32%), and subclinical myocardial dysfunction detected by advanced echocardiographic or PET modalities. Large-scale cohorts identified lupus myocarditis in 1.7%-9% of patients, strongly associated with higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, hypocomplementemia, and anti-nucleosome antibody positivity. Biomarker studies reported elevated troponin, IL-18, IL-1Ra, and interferon-α as predictors of myocardial injury and adverse outcomes. Mortality data linked poor prognosis to myocarditis, pulmonary hypertension, renal disease, and higher comorbidity indices. Outcomes varied, and patients were treated with diverse therapies, including glucocorticoids, immunosuppressants, biologics, and cardiovascular medications. Collectively, findings underscore that cardiac manifestations in SLE are common, multifactorial, and frequently underdiagnosed, with biomarkers and advanced imaging emerging as valuable tools for early detection. Cardiac complications in SLE are prevalent, diverse, and often underrecognized. This review highlights the critical need for improved diagnostic strategies, including the use of emerging biomarkers and advanced imaging techniques, to enable earlier detection and more accurate risk stratification. Standardizing screening protocols and incorporating cardiovascular assessment into routine SLE management may reduce delays in diagnosis and improve patient outcomes. Further research is essential to develop consensus guidelines for early identification and prognostication of cardiac involvement in SLE.

FGF23 excess is associated with morbidity and mortality, but the role of excessive circulating FGF23 concentrations as a causative factor of pathology is controversial. Here, we investigated the consequences of FGF23 excess in kidney disease. This study used three disease models: anti-glomerular basement membrane (anti-GBM) disease, Adriamycin nephropathy, and adenine-containing diets. Anti-GBM and Adriamycin mice and matched control mice received recombinant FGF23 (1 µg) or vehicle for six days (anti-GBM) or once (Adriamycin model), with dissection 24 h after the last injection. We established precision-cut kidney slices (PCKS) in adenine nephropathy for 24 h of treatment with recombinant FGF23 or vehicle. We assessed serum cytokines, biochemistry, and renal transcriptomes and histology of mice and patients with IgA nephropathy. RNA-Seq data and published transcriptomes underwent gene set enrichment, bulk ligand-receptor interaction analysis, and cell-type decomposition. Experimental anti-GBM disease caused decreased glomerular filtration rate, albuminuria, and renal tubular casts. FGF23 treatment increased phosphaturia and circulating soluble tumor necrosis factor receptor 1. The anti-GBM model showed FGF23-driven proinflammatory transcriptional signatures and Vcam1, Pdgfrb, and chemokine signaling, which were absent in FGF23-treated healthy mice. FGF23 increased renal macrophage content by transcriptome deconvolution and by immunofluorescence. In Adriamycin-induced nephropathy and in PCKS from adenine nephropathy, short-term FGF23 excess increased proinflammatory transcripts. Human data revealed associations between circulating FGF23 and renal immune cell infiltration. We found FGF23-driven renal patterns of proinflammatory gene and protein expression or leukocyte overabundance. The present data provide evidence that excess FGF23 directly drives inflammation in kidney disease and may serve as a therapeutic target.