Methylprednisolone pulse therapy combined with mizoribine following tonsillectomy for immunoglobulin A nephropathy: clinical remission rate, steroid sparing effect, and maintenance of renal function

Abstract

BackgroundThe long-term prognosis of immunoglobulin A nephropathy (IgAN) is reportedly poor. In Japan, tonsillectomy-steroid pulse therapy has frequently been used for treatment of early IgAN, with favorable outcomes. However, steroid usage is sometimes limited due to adverse reactions. To reduce the total dose of steroids, we have been using mizoribine (MZR) in combination with tonsillectomy-steroid pulse therapy since 2004. Here we report a retrospective evaluation of our protocol outcome.MethodsForty-two patients aged <70 years with histopathologically confirmed IgAN and an estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m2 or higher were enrolled. After giving informed consent, all the patients underwent bilateral tonsillectomy. One week later, intravenous methylprednisolone pulse therapy (500 mg/day) was administered for 3 days, followed by oral prednisolone (30 mg/day and tapered to 0 over 7 months) and MZR (150 mg/day for 11 months). The complete remission (CR) rate and renoprotective effect were assessed.ResultsThe CR rate at 6, 12, and 24 months was 33.3, 69.1, and 76.2%, respectively. Despite a relatively low total steroid dose, renal function was satisfactorily maintained for 24 months or longer with no relapse. The eGFR in patients with stage 3 chronic kidney disease was significantly improved at 6 months after start of treatment. Three patients (7.1%) had mild and transient adverse events.ConclusionThis protocol appears to be highly effective and safe for IgAN patients with renal dysfunction.

Maintenance treatment using the purine-synthesis inhibitor mizoribine in a patient with relapsing thrombotic thrombocytopenic purpura

“…Moreover, previous basic science studies have suggested that MZR regulates the glucocorticoid receptor function and might enhance the efficacy of corticosteroids [8]. Actually, a previous clinical study reported that the use of MZR for the treatment of nephrotic syndrome [9] and immunoglobulin A nephropathy [10]. These drug profiles indicate that MZR could be useful and safe as a treatment for TTP.…”

Study protocol: high-dose mizoribine with prednisolone therapy in short-term relapsing steroid-sensitive nephrotic syndrome to prevent frequent relapse (JSKDC05 trial)

“…Historically, mizoribine has been used to suppress rejection reactions in kidney transplantation [ 20 , 21 ], lupus nephritis [ 22 , 23 ] and rheumatoid arthritis. Mizoribine has also been reported to be effective as a treatment for IgA nephropathy [ 24 , 25 ]. It is approved as a treatment of NS in Japan [ 3 , 26 ].…”

IgA Nephropathy and Psoriatic Arthritis that Improved with Steroid Pulse Therapy and Mizoribine in Combination with Treatment for Chronic Tonsillitis and Epipharyngitis

“…Therefore, the pathological diagnosis was IgAN with few active lesions, although the lesions were predominantly chronic. We previously reported that the use of steroid pulse therapy in combination with MZR following tonsillectomy is effective in improving urinary findings and preserving the renal function when treating IgA nephropathy in patients with renal impairment (6,7).…”