Combination therapy with mizoribine for severe childhood IgA nephropathy: a pilot study.
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.
Yoshikawa
Norishige
N
Department of Pediatrics, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Japan. nori@wakayama-med.ac.jp
Nakanishi
Koichi
K
Ishikura
Kenji
K
Hataya
Hiroshi
H
Iijima
Kazumoto
K
Honda
Masataka
M
D001706:Biopsy; D002648:Child; D004176:Dipyridamole / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007070:Immunoglobulin A / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D010865:Pilot Projects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011239:Prednisolone / Q000627:therapeutic use; D011446:Prospective Studies; D011507:Proteinuria / Q000473:pathology / Q000652:urine; D012263:Ribonucleosides / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D005938:Glucocorticoids; D007070:Immunoglobulin A; D007166:Immunosuppressive Agents; D010975:Platelet Aggregation Inhibitors; D012263:Ribonucleosides; C010052:mizoribine; D004176:Dipyridamole; D011239:Prednisolone; D007168:IMP Dehydrogenase