Mizoribine treatment for childhood IgA nephropathy.
BACKGROUND
There is currently no established therapy for childhood IgA nephropathy (IgAN). Mizoribine, a newly developed immunosuppressive agent characterized as a safe and well-tolerated drug, has been widely used in diverse conditions. Our preliminary study demonstrated that mizoribine could reduce the amount of proteinuria in children with IgAN. The present study was conducted to confirm this finding.


METHODS
Ten children with IgAN (median age 13.5 years) of moderate histological severity were enrolled. None of them had been previously treated by immunosuppressants. Mizoribine was administered orally for a median period of 20.5 months. We compared the urinary protein excretion expressed as the ratio of urinary protein to urinary creatinine (UP/UC) and the hematuria evaluated as the level of occult blood by dip-stick (OB score). Renal histology was also examined in three patients using paired biopsy specimens obtained both before and after treatment. We performed blood examinations regularly to monitor the toxicity and plasma concentration of mizoribine.


RESULTS
The median observation period was 44.5 months, consisting of a median 13.0 months before therapy, 20.5 months during therapy and 12.0 months after therapy. Significant reductions in both UP/UC and OB score were induced by mizoribine (P < 0.05). Renal mesangial proliferation was also improved. Plasma peak levels of mizoribine varied from 0.30 microg/mL to 1.23 microg/mL and were not associated with its effectiveness. No adverse effects were observed during the therapy, although a slight decrease in leukocyte count was noted.


CONCLUSIONS
Mizoribine can be an alternative drug for childhood IgAN with moderate severity because it results in a significant reduction of proteinuria and hematuria with histological improvement and causes far fewer complications compared to the conventional immunosuppressants.
Nagaoka
Rieko
R
Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan.
Kaneko
Kazunari
K
Ohtomo
Yoshiyuki
Y
Yamashiro
Yuichiro
Y
D000293:Adolescent; D005260:Female; D005922:Glomerulonephritis, IGA / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D012263:Ribonucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine