Anti-glomerular basement membrane disease—treatment standard

We review the current standards of treatment and discuss novel developments in the pathophysiology, diagnosis, outcome prediction and management of anti-glomerular basement membrane (anti-GBM) disease. Anti-GBM disease is a unique form of small vessel vasculitis affecting the glomerular and pulmonary capillaries. It is caused by autoantibodies directed against the α3 chain of type IV collagen, leading to rapidly progressive glomerulonephritis with pulmonary haemorrhage in ∼50% of cases. Diagnosis relies on clinical features, kidney biopsy showing linear IgG deposition along the GBM, and/or detection of circulating anti-GBM antibodies. Historically, untreated disease was rapidly fatal, but the introduction of plasma exchange combined with cyclophosphamide and glucocorticoids has significantly improved outcomes, particularly in patients who are not dialysis-dependent at presentation. Dialysis-dependent patients have a lower likelihood of renal recovery, and treatment decisions must consider biopsy findings, clinical severity and potential contraindications to standard immunosuppression. Unlike anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis, relapses are rare in classic anti-GBM disease, and long-term maintenance immunosuppression is not routinely required. However, 'double positive' patients (anti-GBM and ANCA) have a higher relapse risk and require maintenance immunosuppressive treatment. Atypical anti-GBM presentations, including seronegative cases, are now better recognized but their optimal management remains unclear. Future research should define the use of oral versus intravenous cyclophosphamide in anti-GBM disease, clarify the role of rituximab and determine the place of emerging therapies such as imlifidase. Advances in risk stratification and ongoing trials are expected to inform treatment individualization and to improve treatment approaches for this aggressive autoimmune disease.