What is the treatment for ANCA (Antineutrophil Cytoplasmic Antibody) positive vasculitis with cavitary lesions in patients with Chronic Kidney Disease (CKD)?

From the Guidelines

Treatment of ANCA-positive vasculitis with cavitary lesions in CKD patients should involve a combination of immunosuppressive therapy and supportive care, with rituximab being a preferred option due to its lower nephrotoxicity, as evidenced by the kdigo 2024 clinical practice guideline for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis 1.

Initial Treatment

The initial treatment should include high-dose corticosteroids (prednisone 1 mg/kg/day, maximum 60-80 mg daily) combined with cyclophosphamide or rituximab. For cyclophosphamide, the dose should be adjusted for renal function, typically starting at 2 mg/kg/day orally or 15 mg/kg IV every 2-3 weeks, with further reductions based on GFR.

• Rituximab (375 mg/m² weekly for 4 weeks or 1000 mg given twice, 2 weeks apart) may be preferred in CKD patients due to less nephrotoxicity.
• Cyclophosphamide dose should be reduced for kidney impairment and age, as these patients are at increased risk for infection 1.

Maintenance Therapy

Once remission is achieved (usually within 3-6 months), maintenance therapy with less toxic agents like azathioprine (1-2 mg/kg/day, adjusted for renal function), mycophenolate mofetil (1-2 g/day), or continued low-dose rituximab should be initiated.

• Plasma exchange may be considered for severe disease with pulmonary hemorrhage.
• Prophylaxis against Pneumocystis pneumonia with trimethoprim-sulfamethoxazole (dose-adjusted for renal function) is essential during induction therapy.
• Close monitoring of renal function, complete blood counts, and infection surveillance is crucial, as these patients have increased susceptibility to infections due to both immunosuppression and uremia.

Special Considerations

• Avacopan is an alternative for glucocorticoids for induction of remission in combination with either rituximab or cyclophosphamide, especially in patients with high infection risk, preexisting diabetes mellitus, psychiatric disorders, and osteoporosis, or those with lower kidney function (eGFR <20 ml/min per 1.73 m2) 1.
• Low-dose trimethoprim-sulfamethoxazole (TMP-SMX), or alternative, is advised for pneumocystis pneumonia prophylaxis for the duration of the cyclophosphamide course or for 6 months following rituximab induction 1.
• IgG levels should be measured at baseline and every 6 months for patients treated with rituximab, as low levels at baseline may predict a greater risk of secondary immunodeficiency with rituximab 1.

From the FDA Drug Label

All patients had active disease, with a Birmingham Vasculitis Activity Score for Granulomatosis with Polyangiitis (BVAS/GPA) greater than or equal to 3, and their disease was severe, with at least one major item on the BVAS/GPA. Patients in both arms received 1,000 mg of pulse intravenous methylprednisolone per day for 1 to 3 days within 14 days prior to initial infusion. Patients were randomized in a 1:1 ratio to receive either RITUXAN 375 mg/m2 once weekly for 4 weeks or oral cyclophosphamide 2 mg/kg daily for 3 to 6 months in the remission induction phase The main outcome measure for both GPA and MPA patients was achievement of complete remission at 6 months defined as a BVAS/GPA of 0, and off glucocorticoid therapy

The treatment for ANCA positive vasculitis with cavitary lesions in patients with Chronic Kidney Disease (CKD) is not directly addressed in the provided drug label. However, based on the information provided, the treatment for Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA), which are types of ANCA-associated vasculitis, involves:

• Induction therapy:
  • Rituximab: 375 mg/m2 once weekly for 4 weeks
  • Cyclophosphamide: 2 mg/kg daily for 3 to 6 months
• Glucocorticoids: 1,000 mg of pulse intravenous methylprednisolone per day for 1 to 3 days, followed by oral prednisone with tapering
• Maintenance therapy:
  • Azathioprine: for patients who received cyclophosphamide
  • Rituximab: 500 mg intravenous infusion every 6 months for 18 months, for patients who received rituximab as induction therapy 2

Note: The provided drug label does not specifically address the treatment of ANCA-positive vasculitis with cavitary lesions in patients with CKD. The above information is based on the treatment of GPA and MPA, which may not be directly applicable to the specific condition mentioned in the question.

From the Research

Treatment Options for ANCA-Positive Vasculitis with Cavitary Lesions in CKD Patients

• The treatment for ANCA-positive vasculitis with cavitary lesions in patients with Chronic Kidney Disease (CKD) typically involves immunosuppressive therapy, with the goal of inducing remission and preventing further organ damage 3, 4.
• Rituximab (RTX) is a commonly used treatment option for ANCA-associated vasculitis (AAV), and has been shown to be effective in inducing remission in patients with severe renal disease 3, 4.
• Glucocorticoids (GC) are often used in combination with RTX or other immunosuppressive agents to treat AAV, with the dosing of GC for remission induction in GPA and MPA now lower than previously used 5.
• Cyclophosphamide (CYC) is still an important option for remission induction in severe or refractory organ-threatening disease for all AAVs, although its use is becoming less prominent in favor of biologics such as RTX 6, 5.
• Mycophenolate mofetil (MMF) has been shown to be effective in the treatment of acute c-ANCA-positive vasculitis, and may be used as an alternative to CYC in patients who cannot tolerate it 7.
• Plasma exchange and intravenous immunoglobulins (IVIGs) may be used as adjunctive therapies for induction in certain cases 6.

Treatment Considerations for CKD Patients

• Patients with CKD require careful consideration of treatment options, as they may be at increased risk of adverse events and may require dose adjustments or alternative treatments 3, 4.
• The use of RTX and GC has been shown to be effective in patients with severe renal disease, although the optimal treatment strategy for CKD patients remains unclear 3, 4.
• Further research is needed to determine the best treatment approach for CKD patients with ANCA-positive vasculitis and cavitary lesions, and to address the unanswered questions regarding the duration of remission maintenance treatment and individualized treatment guidance based on biomarkers 5.