[Beneficial and adverse effects of high-dosage MZR therapy in the management of children with frequently relapsing nephrotic syndrome].
BACKGROUND
Long-term therapy of mizoribine (MZR 2-5 mg/kg/day) has been reported in the management of children with frequently relapsing nephrotic syndrome(FRNS). It had minimum adverse effects, however, MZR therapy does not sufficiently suppress the relapse of FRNS. Previous reports suggested that modification of MZR therapy with a total dosage and administration schedule may improve the therapeutic effect. To elucidate the issue, we retrospectively evaluated the efficacy and safety of high-dose MZR therapy for children with FRNS.


METHODS
The subjects comprised 13 affected children with FRNS (9 boys and 4 girls: median age of 11.7 years, ranging from 7.8 to 20.1 years). They were divided into a high dose group (MZR 7-10 mg/kg/ day; Max 400 mg) and a low dose group (MZR 4-6 mg/kg/day). We compared the therapeutic benefits between both groups, including the incidence of relapse(times/year) and daily dosages of prednisolone (PSL, mg/kg/day). The Wilcoxon test was used for statistical analysis. We also evaluated the relationship between the therapeutic effects and serum concentration of MZR two hours after the administration.


RESULTS
The low dose and high-dose groups were well matched in terms of baseline characteristics. After the initiation of MZR, beneficial therapeutic effects ensued in the high-dose group (incidence of relapse: 3.61 vs. 1.59 times/year before and after the therapy, p < 0.05), daily dosages of PSL (0.65 vs. 0.29 mg/kg/day before and after therapy, p<0.001), but did not occur in the low-dose group(3.97 vs. 2.84 times/year; 0.84 vs. 0.53 mg/kg/day, n. s.). All patients with a serum MZR concentration of over 3 microg/ml had relapses less than three times a year. One patient in the high-dose group and the other in the low-dose group showed hyperuricemia, and responded well to medical treatment. No other adverse effect was observed.


CONCLUSIONS
High-dose MZR therapy in the management for FRNS may provide more beneficial effects without significant adverse effects.
Goto
Miwa
M
Department of Pediatric Nephrology, Tokyo Metropolitan Kiyose Children's Hospital, Japan.
Ikeda
Masahiro
M
Hataya
Hiroshi
H
Ishikura
Kenji
K
Hamasaki
Yuko
Y
Honda
Masataka
M
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy*; D011239:Prednisolone / Q000008:administration & dosage; D012008:Recurrence; D012189:Retrospective Studies; D012263:Ribonucleosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine; D011239:Prednisolone