Anti‑glomerular basement membrane (anti‑GBM) disease is a rare autoimmune cause of rapidly progressive glomerulonephritis (RPGN). It is characterized by autoantibodies directed against the non‑collagenous domain of the α3 chain of type IV collagen. While pulmonary hemorrhage is a classical feature, renal‑limited forms are increasingly recognized and pose diagnostic challenges. We report a 73‑year‑old woman with previously normal renal function who presented with anorexia, nausea, exertional breathlessness, pedal edema, and anuria. Laboratory evaluation revealed severe azotemia and markedly elevated anti‑GBM antibody titres. Renal biopsy demonstrated diffuse crescentic glomerulonephritis with linear IgG deposition along the GBM. She required hemodialysis and was initiated on immunosuppression with glucocorticoids, cyclophosphamide, and plasma exchange. This case underscores the importance of early recognition of renal‑limited anti‑GBM disease, even in the absence of pulmonary involvement, and highlights the prognostic implications of histological findings.
Anti‑GBM disease is an uncommon autoimmune small‑vessel vasculitis, with an incidence of approximately 0.5–1 case per million population annually. It is mediated by autoantibodies targeting the α3 chain of type IV collagen, leading to complement activation, neutrophil recruitment, and glomerular injury. Clinically, patients often present with a combination of renal and pulmonary involvement, termed Goodpasture’s syndrome. However, renal‑limited phenotypes are increasingly recognized, particularly in elderly patients, and may be overlooked in the absence of pulmonary hemorrhage. The disease course is fulminant, with rapid progression to end‑stage renal disease if untreated. Early diagnosis and prompt initiation of therapy are essential to improve outcomes.¹,²
A 73‑year‑old woman, known to have type 2 diabetes mellitus and hypertension for fifteen years, presented with a one‑month history of anorexia and nausea. This was followed by exertional breathlessness for seven days, bilateral pedal edema for three days, and anuria for one day. She had been apparently well until one month prior to admission, when she developed progressive anorexia and nausea. Her baseline serum creatinine was 0.9 mg/dL in April 2026, with no previously documented renal dysfunction. On examination, she was pale, with bilateral pitting pedal edema. Her blood pressure was 100/68 mmHg, pulse rate 80/min, and oxygen saturation 99% on room air. Cardiovascular, respiratory, abdominal, and neurological examinations were otherwise unremarkable. Importantly, there was no history of hemoptysis, cough, fever, rash, arthralgia, oral ulcers, gross hematuria, dysuria, or exposure to non‑steroidal anti‑inflammatory drugs or native medications.
Initial laboratory evaluation revealed severe azotemia, with a blood urea nitrogen of 110 mg/dL and serum creatinine of 6.98 mg/dL compared with her baseline of 0.9 mg/dL. Serum sodium was 123 mmol/L and potassium 4.5 mmol/L. Hemoglobin was 8.3 g/dL, with leukocytosis (19,160/µL) and thrombocytosis (6.69 lakh/µL). In view of the rapid deterioration in renal function, oliguria progressing to anuria, and clinical evidence of volume overload, RPGN was considered the principal clinical syndrome.
Serological evaluation revealed preserved complement levels (C3 106 mg/dL, C4 23 mg/dL). Antinuclear antibody and ANCA were negative. Anti‑GBM antibody was markedly elevated at 151 U/mL. Blood cultures showed no growth. The combination of rapidly progressive renal failure, negative ANA and ANCA, preserved complement levels, and strongly positive anti‑GBM serology raised suspicion of anti‑GBM disease. The absence of pulmonary symptoms or clinical evidence of alveolar hemorrhage suggested a renal‑limited presentation.
A native renal biopsy performed on the fifth day of admission demonstrated diffuse crescentic glomerulonephritis. Of 39 glomeruli sampled, six were globally sclerosed. Crescents were present in 29 glomeruli, including 15 cellular, two fibrocellular, and 12 fibrous crescents. Fibrinoid necrosis of glomerular tufts was observed, with rupture of Bowman’s capsule, dense lymphohistiocytic inflammation, and focal giant‑cell reaction. The four relatively uninvolved glomeruli showed mesangial expansion and proliferation without definite basement membrane thickening or endocapillary hypercellularity. The tubulointerstitium demonstrated diffuse dense mixed inflammation comprising lymphocytes, plasma cells, histiocytes, numerous neutrophils, and occasional eosinophils. Proximal tubules showed neutrophilic casts, intraluminal red blood cells, coarse cytoplasmic vacuolation, and moderate acute tubular injury. Interstitial fibrosis and tubular atrophy involved approximately 10–15% of the cortex. Moderate arteriolar hyalinosis and mild fibrointimal thickening of arteries were also noted.
Direct immunofluorescence performed on a core containing seven glomeruli demonstrated strong (3+) linear, ribbon‑like staining for IgG and C3 along the glomerular basement membranes. Kappa and lambda light chains showed 2+ linear staining, while IgA, IgM, and C1q were negative. The characteristic diffuse linear deposition of IgG along the GBM, in conjunction with extensive necrotizing crescentic glomerulonephritis and markedly elevated circulating anti‑GBM antibody level, was diagnostic of anti‑GBM glomerulonephritis. Linear IgG deposition along the GBM is the characteristic immunopathological feature of anti‑GBM disease and reflects autoantibody binding to the non‑collagenous domain of the α3 chain of type IV collagen.¹,²
Based on the clinical presentation, serological findings, and renal histopathology, a diagnosis of anti‑GBM disease presenting as severe renal‑limited crescentic RPGN was established. The absence of hemoptysis, respiratory symptoms, or other evidence of pulmonary hemorrhage indicated an isolated renal phenotype.
In view of severe renal failure with progressive oliguria/anuria and volume overload, a right internal jugular double‑lumen dialysis catheter was inserted on the second day of admission, and intermittent hemodialysis was initiated. Following confirmation of anti‑GBM disease, treatment was planned with disease‑directed immunosuppression and plasma exchange. Current guidelines recommend prompt initiation of plasma exchange in combination with glucocorticoids and cyclophosphamide in appropriate patients with active anti‑GBM disease, with the objective of removing circulating pathogenic antibodies and suppressing further autoantibody production.²
The renal biopsy demonstrated extensive glomerular involvement, with crescents in approximately 74% of sampled glomeruli. However, the predominance of cellular rather than fibrous crescents and the relatively limited degree of interstitial fibrosis and tubular atrophy suggested that a component of the renal injury remained potentially reversible. Conversely, the presence of anuria, dialysis dependence at presentation, fibrinoid necrosis, extensive crescent formation, and six globally sclerosed glomeruli represented adverse prognostic features. Renal outcome in anti‑GBM disease is strongly influenced by the severity and chronicity of renal injury at presentation, with dialysis dependence and extensive irreversible histological injury being associated with a lower likelihood of renal recovery.³
Anti‑GBM disease is distinguished histologically by necrotizing crescentic glomerulonephritis and immunopathologically by diffuse linear IgG deposition along the GBM. This pattern distinguishes anti‑GBM disease from pauci‑immune crescentic glomerulonephritis, in which immunofluorescence shows little or no immune deposition, and from immune‑complex crescentic glomerulonephritis, which demonstrates granular immune deposition.⁴ The present case is notable for the patient’s advanced age, rapid progression from previously normal renal function to dialysis‑requiring anuric renal failure, and the absence of pulmonary involvement. The markedly elevated anti‑GBM antibody titre and characteristic linear IgG staining on renal biopsy established the diagnosis despite the absence of pulmonary manifestations. The coexistence of cellular, fibrocellular, and fibrous crescents provides evidence of both active and established glomerular injury, while the relatively modest degree of tubulointerstitial fibrosis may have implications for the potential reversibility of renal dysfunction.
Renal‑limited anti‑GBM disease is an important and potentially life‑threatening cause of rapidly progressive renal failure in elderly patients. The absence of pulmonary manifestations should not delay consideration of anti‑GBM disease. Early recognition through appropriate serological testing and renal biopsy is essential, as prompt initiation of disease
McAdoo SP, Pusey CD. Anti-glomerular basement membrane disease. Clin J Am Soc Nephrol. 2017;12(7):1162-1172.
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4S):S1-S276.
Levy JB, Turner AN, Rees AJ, Pusey CD. Long-term outcome of anti-glomerular basement membrane antibody
Dr M Tamilaruvi Postgraduate in Nephrology Kauvery Hospital, Chennai.
Dr R Balasubramaniam Chief Nephrologist and Senior Consultant Kauvery Hospital, Chennai.
Dr Sangamitra Consultant Pathologist Kauvery Hospital, Chennai.
