title: A randomized open-label comparative study of conventional therapy versus mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome (postmarketing survey).
abstract: BACKGROUND
  A previous double-blind 24-week clinical trial of mizoribine (MZ) vs placebo in steroid-resistant primary nephrotic syndrome (SRPNS) showed that MZ was more effective than placebo in reducing the rate of deterioration of renal function. The present study was conducted to evaluate the efficacy and safety of MZ in patients with SRPNS after 2 years' treatment.
  
  
  METHODS
  A multicenter randomized open-label controlled trial in patients with SRPNS was conducted as a 2-year prospective postmarketing study.
  
  
  RESULTS
  There was a significant imbalance in the baseline serum albumin level (s-Alb) between the conventional therapy (CT) and MZ onlay therapy groups. Early dropouts were more frequent in the subset of patients in the CT group having a baseline s-Alb < or =3 g/dl. Therefore, the primary analysis (urinary protein level (UP)-improving effect) was performed using a mixed-effects model, with stratification according to the baseline s-Alb value. The analysis revealed that, in the subset of 34 patients with membranous nephropathy (MN) within the stratum of patients with baseline s-Alb < or =3 g/dl (n = 52), the rate of change (slope of change in the UP level/month), in terms of the log (UP+0.2), was -0.0577 in those allocated to the MZ group and -0.0227 in those allocated to the CT group (P = 0.058). In the stratum of patients with a baseline s-Alb >3 g/dl (n = 97), there were no significant differences in the UP between the two treatment groups. Hence, MZ onlay therapy was not considered to be efficacious in this group of patients. No serious adverse reactions to the drug were observed.
  
  
  CONCLUSIONS
  The present study yielded significant results, in that it suggested the possibility that long-term MZ therapy may afford further reduction of the UP, in addition to that obtained following CT, in particular, in MN patients in a severe nephrotic state.
authors.affiliation: Department of Pharmacotherapeutics, Kyoritsu College of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. shibasaki-ts@kyoritsu.ph.ac.jp
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shibasaki
authors.forename: Akio
authors.initials: A
authors.lastname: Koyama
authors.forename: Akira
authors.initials: A
authors.lastname: Hishida
authors.forename: Eri
authors.initials: E
authors.lastname: Muso
authors.forename: Gengo
authors.initials: G
authors.lastname: Osawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yamabe
authors.forename: Hideo
authors.initials: H
authors.lastname: Shiiki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Isao
authors.initials: I
authors.lastname: Ishikawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Maeda
authors.forename: Kimio
authors.initials: K
authors.lastname: Tomita
authors.forename: Masaaki
authors.initials: M
authors.lastname: Arakawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Ishida
authors.forename: Masashi
authors.initials: M
authors.lastname: Sato
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Nagase
authors.forename: Naoki
authors.initials: N
authors.lastname: Kashihara
authors.forename: Noriaki
authors.initials: N
authors.lastname: Yorioka
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
authors.forename: Takao
authors.initials: T
authors.lastname: Saito
authors.forename: Takashi
authors.initials: T
authors.lastname: Harada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitarai
authors.forename: Tetsuzo
authors.initials: T
authors.lastname: Sugisaki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nagasawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Osamu
authors.initials: O
authors.lastname: Sakai
mesh_terms: D000328:Adult; D004351:Drug Resistance; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000188:drug therapy*; D010352:Patient Dropouts; D011358:Product Surveillance, Postmarketing; D011507:Proteinuria / Q000188:drug therapy; D012074:Remission Induction; D012263:Ribonucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D013256:Steroids / Q000008:administration & dosage
chemical_list: D007166:Immunosuppressive Agents; D012263:Ribonucleosides; D013256:Steroids; C010052:mizoribine