A randomized open-label comparative study of conventional therapy versus mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome (postmarketing survey)

Toshiaki Shibasaki, Akio Koyama, Akira Hishida, Eri Muso, Gengo Osawa, Hideaki Yamabe, Hideo Shiiki, Hirofumi Makino, Hiroshi Sato, Isao Ishikawa, Kenji Maeda, Kimio Tomita, Masaaki Arakawa, Masashi Ishida, Masashi Sato, Mitsumasa Nagase, Naoki Kashihara, Noriaki Yorioka, Takao Koike, Takao SaitoTakashi Harada, Tetsuya Mitarai, Tetsuzo Sugisaki, Toshihiko Nagasawa, Yasuhiko Tomino, Yoshihisa Nojima, Yutaka Kobayashi, Osamu Sakai

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 ≤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 ≤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.

Original languageEnglish
Pages (from-to)117-126
Number of pages10
JournalClinical and Experimental Nephrology
Volume8
Issue number2
DOIs
Publication statusPublished - Jan 1 2004

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Inlays
Nephrotic Syndrome
Steroids
Serum Albumin
Group Psychotherapy
Membranous Glomerulonephritis
Therapeutics
Proteins
Placebos
Surveys and Questionnaires
bredinin
Drug-Related Side Effects and Adverse Reactions
Clinical Trials
Prospective Studies
Kidney
Safety

Keywords

  • Immunosuppressants
  • Membranous nephropathy
  • Mixed model
  • Mizoribine
  • Nephrotic syndrome

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Physiology (medical)

Cite this

A randomized open-label comparative study of conventional therapy versus mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome (postmarketing survey). / Shibasaki, Toshiaki; Koyama, Akio; Hishida, Akira; Muso, Eri; Osawa, Gengo; Yamabe, Hideaki; Shiiki, Hideo; Makino, Hirofumi; Sato, Hiroshi; Ishikawa, Isao; Maeda, Kenji; Tomita, Kimio; Arakawa, Masaaki; Ishida, Masashi; Sato, Masashi; Nagase, Mitsumasa; Kashihara, Naoki; Yorioka, Noriaki; Koike, Takao; Saito, Takao; Harada, Takashi; Mitarai, Tetsuya; Sugisaki, Tetsuzo; Nagasawa, Toshihiko; Tomino, Yasuhiko; Nojima, Yoshihisa; Kobayashi, Yutaka; Sakai, Osamu.

In: Clinical and Experimental Nephrology, Vol. 8, No. 2, 01.01.2004, p. 117-126.

Research output: Contribution to journalArticle

Shibasaki, T, Koyama, A, Hishida, A, Muso, E, Osawa, G, Yamabe, H, Shiiki, H, Makino, H, Sato, H, Ishikawa, I, Maeda, K, Tomita, K, Arakawa, M, Ishida, M, Sato, M, Nagase, M, Kashihara, N, Yorioka, N, Koike, T, Saito, T, Harada, T, Mitarai, T, Sugisaki, T, Nagasawa, T, Tomino, Y, Nojima, Y, Kobayashi, Y & Sakai, O 2004, 'A randomized open-label comparative study of conventional therapy versus mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome (postmarketing survey)', Clinical and Experimental Nephrology, vol. 8, no. 2, pp. 117-126. https://doi.org/10.1007/s10157-004-0276-0
Shibasaki, Toshiaki ; Koyama, Akio ; Hishida, Akira ; Muso, Eri ; Osawa, Gengo ; Yamabe, Hideaki ; Shiiki, Hideo ; Makino, Hirofumi ; Sato, Hiroshi ; Ishikawa, Isao ; Maeda, Kenji ; Tomita, Kimio ; Arakawa, Masaaki ; Ishida, Masashi ; Sato, Masashi ; Nagase, Mitsumasa ; Kashihara, Naoki ; Yorioka, Noriaki ; Koike, Takao ; Saito, Takao ; Harada, Takashi ; Mitarai, Tetsuya ; Sugisaki, Tetsuzo ; Nagasawa, Toshihiko ; Tomino, Yasuhiko ; Nojima, Yoshihisa ; Kobayashi, Yutaka ; Sakai, Osamu. / A randomized open-label comparative study of conventional therapy versus mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome (postmarketing survey). In: Clinical and Experimental Nephrology. 2004 ; Vol. 8, No. 2. pp. 117-126.
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T1 - A randomized open-label comparative study of conventional therapy versus mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome (postmarketing survey)

AU - Shibasaki, Toshiaki

AU - Koyama, Akio

AU - Hishida, Akira

AU - Muso, Eri

AU - Osawa, Gengo

AU - Yamabe, Hideaki

AU - Shiiki, Hideo

AU - Makino, Hirofumi

AU - Sato, Hiroshi

AU - Ishikawa, Isao

AU - Maeda, Kenji

AU - Tomita, Kimio

AU - Arakawa, Masaaki

AU - Ishida, Masashi

AU - Sato, Masashi

AU - Nagase, Mitsumasa

AU - Kashihara, Naoki

AU - Yorioka, Noriaki

AU - Koike, Takao

AU - Saito, Takao

AU - Harada, Takashi

AU - Mitarai, Tetsuya

AU - Sugisaki, Tetsuzo

AU - Nagasawa, Toshihiko

AU - Tomino, Yasuhiko

AU - Nojima, Yoshihisa

AU - Kobayashi, Yutaka

AU - Sakai, Osamu

PY - 2004/1/1

Y1 - 2004/1/1

N2 - 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 ≤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 ≤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.

AB - 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 ≤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 ≤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.

KW - Immunosuppressants

KW - Membranous nephropathy

KW - Mixed model

KW - Mizoribine

KW - Nephrotic syndrome

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