Anti-glomerular basement membrane disease: A contemporary case series from a large university hospital center

Anti-glomerular basement membrane disease (anti-GBM) is a rare autoimmune disorder characterized by autoantibodies targeting antigens in the glomerular and alveolar basement membranes, often leading to rapidly progressive glomerulonephritis and pulmonary hemorrhage. Contemporary real-world data on clinical presentation and long-term renal outcomes remain scarce. This study aims to examine the clinical and pathological features, as well as renal survival and long-term outcomes, in patients with anti-GBM disease.

Retrospective single-center case series.

All patients diagnosed with anti-GBM disease at a major Portuguese university hospital between 2003 and 2023 were included. Anti-GBM disease was defined as a compatible clinical presentation plus positive anti-GBM antibodies in circulation and/or biopsy-proven anti-GBM disease. Demographic, clinical, laboratory and therapeutic data were reviewed.

Twenty-seven patients were included (mean age 58.7±22.0 years; 59.3% female). Renal involvement was universal and severe (mean serum creatinine 11.95±10.18mg/dL), with 92.6% requiring renal replacement therapy (RRT) at presentation. Alveolar hemorrhage occurred in 33.3% patients. Anti-GBM antibodies were detected in 92.6%; 29.6% were also ANCA-positive. Kidney biopsy (n=15) showed crescentic glomerulonephritis in 80% with a mean crescent burden of 60.9% and a median of 0% normal glomeruli (IQR 0-1). Most patients (92%) received immunosuppressive therapy, and 68% were treated with the standard combination of corticosteroids, cyclophosphamide, and plasma exchange. Renal recovery was limited: only 5 patients (18.5%) who required RRT at presentation recovered renal function, and 66.7% progressed to end-stage kidney disease (ESKD). Higher baseline serum creatinine, a lower proportion of normal glomeruli, and crescentic involvement >40% were significantly associated with ESKD. One- and five-year patient survival were 85.2% and 74.1%, respectively. No relapses occurred.

Anti-GBM disease in this Portuguese cohort presented predominantly with severe acute kidney injury requiring RRT and was associated with poor renal recovery despite guideline-directed therapy. Histologic preservation of normal glomeruli and baseline kidney function were strongly associated with renal outcomes. These findings underscore the need for earlier recognition and timely referral, as well as the development of more effective targeted therapies for this severe glomerular disease.