Combination therapy with mizoribine for severe childhood IgA nephropathy: a pilot study.

Abstract

In two previous randomized controlled trials we showed that treatment of severe childhood immunoglobulin A nephropathy (IgA-N) using prednisolone, azathioprine, heparin-warfarin, and dipyridamole prevented any increase of sclerosed glomeruli and that prednisolone alone did not prevent a further increase of sclerosed glomeruli. Accordingly, the immunosuppressant is considered to be important. Often, however, we were unable to complete azathioprine regimen due to toxicity. Therefore, a different but effective immunosuppressant may be worth trying. Mizoribine, like azathioprine, is an antimetabolite that exerts its immunosuppressant effect by inhibiting lymphocyte proliferation. In this pilot study, we administered mizoribine instead of azathioprine as part of the combination therapy for treating 23 children with severe IgA-N and evaluated the efficacy and safety. Eighteen patients reached the primary endpoint (urine protein/creatinine ratio <0.2) during the 2-year treatment period. The cumulative disappearance rate of proteinuria determined by Kaplan-Meier was 80.4%. Median protein excretion was reduced from 1.19 g/m(2)/day to 0.05 g/m(2)/day (p < 0.0001). After treatment, the median percentage of glomeruli showing sclerosis was unchanged in comparison with that before treatment. No patients required a change of treatment. In conclusion, the efficacy and safety of the mizoribine combination seems to be acceptable for treating children with severe IgA-N.

• Authors: Norishige Yoshikawa, Koichi Nakanishi, Kenji Ishikura, Hiroshi Hataya, Kazumoto Iijima, Masataka Honda, Japanese Pediatric IgA Nephropathy Treatment Study Group
• Journal: Pediatric nephrology (Berlin, Germany) (Pediatr Nephrol) Vol. 23 Issue 5 Pg. 757-63 (May 2008) ISSN: 0931-041X [Print] Germany
• PMID: 18224343 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Glucocorticoids
• Immunoglobulin A
• Immunosuppressive Agents
• Platelet Aggregation Inhibitors
• Ribonucleosides
• mizoribine
• Dipyridamole
• Prednisolone
• IMP Dehydrogenase

Topics

• Biopsy
• Child
• Dipyridamole (therapeutic use)
• Disease Progression
• Female
• Follow-Up Studies
• Glomerulonephritis, IGA (drug therapy, metabolism, pathology)
• Glucocorticoids (therapeutic use)
• Humans
• IMP Dehydrogenase (antagonists & inhibitors)
• Immunoglobulin A (blood)
• Immunosuppressive Agents (therapeutic use)
• Kidney Glomerulus (pathology)
• Male
• Pilot Projects
• Platelet Aggregation Inhibitors (therapeutic use)
• Prednisolone (therapeutic use)
• Prospective Studies
• Proteinuria (pathology, urine)
• Ribonucleosides (therapeutic use)
• Severity of Illness Index
• Treatment Outcome