Efficacy of Steroid Pulse Therapy in Combination with Mizoribine Following Tonsillectomy for Immunoglobulin A Nephropathy in Renally Impaired Patients

Abstract

Background: The long-term prognosis of immunoglobulin A nephropathy is poor. Treatment is intended to achieve complete remission in the early stage or to preserve renal function in the advanced stages. In Japan, aggressive steroid pulse therapy following tonsillectomy (tonsillectomy-pulse therapy) has recently been used to treat early IgA nephropathy and has achieved favorable outcomes. However, steroid doses are sometimes limited because of adverse reactions s and the efficacy of tonsillectomy-steroid pulse therapy has not been established in patients with renal dysfunction. In our current treatment protocol, the total steroid dose has been significantly reduced through the use of the immunosuppressant mizoribine in combination with tonsillectomy-steroid pulse therapy for the treatment of active IgA nephropathy in patients with renal impairment.
Methods: The subjects were 18 patients with active IgA nephropathy who were younger than 70 years and had an estimated glomerular filtration rate ≥20 and <60 mL/min/1.73 m². After giving informed consent, the patients underwent bilateral tonsillectomy. One week later, intravenous methylprednisolone pulse therapy (500 mg/day) was administered for 3 days, followed by oral prednisolone in combination with mizoribine (100 to 150 mg/day). A renin-angiotensin system inhibitor was used before tonsillectomy in all cases. One year after tonsillectomy, the safety of this protocol and its effects on hematuria, proteinuria, and the progression of renal dysfunction were assessed.
Results: The mean patient age was 48.4 years, and the mean time from disease onset to tonsillectomy was 8.4 years. After 1 year, urinary protein had decreased (1.80 ± 1.36 to 0.47 ± 0.75 g/g・Cr) in all cases but 1 and had resolved completely in 38.9% of cases. Hematuria had decreased in all cases and had resolved completely in 61.1% of cases. The estimated glomerular filtration rate also improved in all cases and the mean increased significantly from 42.4 ± 11.9 to 50.1 ± 15.9 mL/min/1.73 m². No serious complications were found during follow-up. Steroid acne that required treatment occurred in 2 cases (11.1%) but was transient and mild.
Conclusion: Steroid pulse therapy in combination with mizoribine following tonsillectomy is effective in improving urinary findings and preserving renal function in the treatment of IgA nephropathy, which remained active in patients with renal impairment (estimated glomerular filtration rate ≥20 and <60 mL/min/1.73 m²).