From the Guidelines
Patients with double-positive Anti-Neutrophil Cytoplasmic Antibodies (ANCA) and Anti-Glomerular Basement Membrane (Anti-GBM) antibodies in Rapidly Progressive Glomerulonephritis (RPGN) have a poor kidney prognosis and require aggressive immunosuppression with high-dose corticosteroids, cyclophosphamide, and plasma exchange, as well as maintenance immunosuppression due to the high risk of relapse. This condition is uncommon, representing only about 5-14% of all RPGN cases, and typically carries a worse prognosis than either condition alone 1. The treatment approach should be similar to that of anti-GBM disease, with the addition of maintenance immunosuppression due to the presence of ANCA antibodies, which increases the risk of relapse 1.
Key Considerations
- The patient likely presented with symptoms such as hematuria, proteinuria, and declining kidney function, and diagnosis would have been confirmed through kidney biopsy showing crescentic glomerulonephritis along with positive serologies for both ANCA and anti-GBM antibodies.
- Early recognition and aggressive treatment are crucial as this condition can rapidly progress to end-stage kidney disease if not promptly addressed.
- Plasma exchange should be initiated daily for 14 days or until anti-GBM antibodies are undetectable, as recommended by the 2021 KDIGO clinical practice guideline for the management of glomerular diseases 1.
- Maintenance immunosuppression is necessary for patients with double-positive disease, as they are at high risk of relapse, unlike those with anti-GBM disease alone, who rarely relapse 1.
Treatment Approach
- Aggressive immunosuppression with high-dose corticosteroids, such as methylprednisolone 500-1000mg IV daily for 3 days, followed by oral prednisone 1mg/kg/day.
- Cyclophosphamide, either 2mg/kg/day orally or 15mg/kg IV every 2-3 weeks, as an alternative to rituximab in some cases.
- Plasma exchange, typically 7-14 sessions, daily for 14 days or until anti-GBM antibodies are undetectable.
- Maintenance immunosuppression to prevent relapse, as recommended by the 2021 KDIGO clinical practice guideline for the management of glomerular diseases 1.
From the Research
Clinical Significance of Double-Positive ANCA and Anti-GBM Antibodies in RPGN
- The presence of both Anti-Neutrophil Cytoplasmic Antibodies (ANCA) and Anti-Glomerular Basement Membrane (Anti-GBM) antibodies in patients with Rapidly Progressive Glomerulonephritis (RPGN) is associated with a poor renal prognosis 2, 3, 4.
- Patients with double-positive ANCA and Anti-GBM antibodies often exhibit severe clinical presentations, including acute kidney failure and alveolar hemorrhage 4.
- The majority of patients with double-positive ANCA and Anti-GBM antibodies have ANCAs directed against myeloperoxidase (MPO) rather than proteinase 3 (PR3) 4.
Treatment and Outcomes
- Aggressive treatment approaches, including plasma exchange, immunosuppressive therapy, and novel combinations of glucocorticoids, rituximab, and cyclophosphamide, may be effective in managing patients with double-positive ANCA and Anti-GBM antibodies 2, 3, 5.
- Despite aggressive treatment, the one-year overall, renal, and relapse-free survival rates for patients with double-positive ANCA and Anti-GBM antibodies are relatively poor, highlighting the need for early recognition and treatment of this condition 4.
- Some patients may achieve dialysis independence and remission of glomerulonephritis with intensive therapy, although renal function recovery is not always obtained 2, 3, 6.
Diagnostic Considerations
- Simultaneous testing of both ANCA and Anti-GBM antibodies, as well as systematic renal biopsy, is recommended in every patient with RPGN to recognize this difficult-to-treat and rare disease 4.
- The diagnosis of double-positive ANCA and Anti-GBM antibodies should be considered in patients with RPGN, particularly those with severe clinical presentations and poor renal prognosis 2, 3, 4.