Randomized Controlled Trial

. 2015 Jan;87(1):225-32.

doi: 10.1038/ki.2014.260. Epub 2014 Jul 23.

A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment

Norishige Yoshikawa¹, Koichi Nakanishi¹, Mayumi Sako², Mari S Oba³, Rintaro Mori⁴, Erika Ota⁴, Kenji Ishikura⁵, Hiroshi Hataya⁵, Masataka Honda⁵, Shuichi Ito⁶, Yuko Shima¹, Hiroshi Kaito⁷, Kandai Nozu⁷, Hidefumi Nakamura², Takashi Igarashi⁸, Yasuo Ohashi⁹, Kazumoto Iijima⁷; Japanese Study Group of Kidney Disease in Children

Collaborators, Affiliations

Collaborators

Japanese Study Group of Kidney Disease in Children:
Norishige Yoshikawa, Kazumoto Iijima, Hidefumi Nakamura, Masataka Honda, Mayumi Sako, Koichi Nakanishi, Yuko Shima, Yasuo Ohashi, Mari S Oba, Takashi Igarashi, Yasuo Ohashi, Tetsuya Kawamura, Michio Nagata, Satoshi Sasaki, Yutaka Yamada, Tetsuro Nagashima, Yoshinori Saita, Tetsuji Morimoto, Yohei Ikezumi, Toshio Yanagihara, Noriko Oonishi, Tomoko Sato, Kenji Nemoto, Katsutoshi Nagasawa, Masahiko Katayose, Yoshiyuki Namai, Shigeo Suzuki, Yasuaki Kobayashi, Yoko Owada, Hideaki Kurayama, Shuichiro Fujinaga, Midori Awazu, Hirotaka Takahashi, Shori Takahashi, Motoshi Hattutori, Shuichi Ito, Koichi Kamei, Masayasu Ohta, Tae Omori, Nobuyuki Kurosawa, Masuhiro Shimoda, Shiro Tsuchiya, Kenichiro Miura, Atsushi Inatomi, Yoshiyuki Otomo, Tomonosuke Someya, Shoichi Oyama, Hiroshi Hataya, Kenji Ishikura, Takeshi Matsuyama, Masahiro Banba, Kiyoshi Araki, Hitoshi Wakaki, Cho Hideo, Tomonori Harada, Tomoko Nakamura, Shoko Goto, Fumio Niimura, Naohiro Wada, Masami Shirai, Kozo Muto, Osamu Uemura, Yoshimitsu Goto, Naoya Fujita, Kazuhide Ohta, Masaki Shimizu, Koichi Tsukahara, Yukiko Mori, Hiroshi Akutagawa, Toshihiro Sawai, Kashiro Nishizawa, Akira Ashida, Naohisa Kawamura, Takuya Tanabe, Koji Taira, Seiji Kinoshita, Shinya Tanaka, Nobuhiko Shimizu, Katsuhisa Yamamoto, Shinichi Sumimoto, Koichi Nakanishi, Noriyuki Aoyagi, Seiji Iwahashi, Masakazu Miyawaki, Ritsuko Miyashita, Masamitsu Nishino, Daisuke Hata, Mikio Goto, Ryojiro Tanaka, Kandai Nozu, Hiroshi Kaito, Sakiko Konohana, Ichiro Kamioka, Masayuki Yamane, Katsuji Kuwakado, Shoji Kagami, Yuhei Ito, Yoshihiko Murakami, Jiro Iwamoto, Yoshitsugu Kaku, Kentaro Kamesaki, Ken Hatae, Hitoshi Nakazato, Yasushi Otsuka, Tomohiro Ichimaru, Tadashi Sato

Affiliations

¹ Department of Pediatrics, Wakayama Medical University, Wakayama City, Japan.
² Division for Clinical Trials, Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan.
³ Department of Biostatistics and Epidemiology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
⁴ Department of Health Policy, National Center for Child Health and Development, Tokyo, Japan.
⁵ Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
⁶ Department of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan.
⁷ Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
⁸ National Center for Child Health and Development, Tokyo, Japan.
⁹ Department of Biostatistics, School of Public Health, The University of Tokyo, Tokyo, Japan.

PMID: 25054775
PMCID: PMC4284810
DOI: 10.1038/ki.2014.260

Free PMC article

Randomized Controlled Trial

A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment

Norishige Yoshikawa et al. Kidney Int. 2015 Jan.

Free PMC article

. 2015 Jan;87(1):225-32.

doi: 10.1038/ki.2014.260. Epub 2014 Jul 23.

Authors

Collaborators

Japanese Study Group of Kidney Disease in Children:
Norishige Yoshikawa, Kazumoto Iijima, Hidefumi Nakamura, Masataka Honda, Mayumi Sako, Koichi Nakanishi, Yuko Shima, Yasuo Ohashi, Mari S Oba, Takashi Igarashi, Yasuo Ohashi, Tetsuya Kawamura, Michio Nagata, Satoshi Sasaki, Yutaka Yamada, Tetsuro Nagashima, Yoshinori Saita, Tetsuji Morimoto, Yohei Ikezumi, Toshio Yanagihara, Noriko Oonishi, Tomoko Sato, Kenji Nemoto, Katsutoshi Nagasawa, Masahiko Katayose, Yoshiyuki Namai, Shigeo Suzuki, Yasuaki Kobayashi, Yoko Owada, Hideaki Kurayama, Shuichiro Fujinaga, Midori Awazu, Hirotaka Takahashi, Shori Takahashi, Motoshi Hattutori, Shuichi Ito, Koichi Kamei, Masayasu Ohta, Tae Omori, Nobuyuki Kurosawa, Masuhiro Shimoda, Shiro Tsuchiya, Kenichiro Miura, Atsushi Inatomi, Yoshiyuki Otomo, Tomonosuke Someya, Shoichi Oyama, Hiroshi Hataya, Kenji Ishikura, Takeshi Matsuyama, Masahiro Banba, Kiyoshi Araki, Hitoshi Wakaki, Cho Hideo, Tomonori Harada, Tomoko Nakamura, Shoko Goto, Fumio Niimura, Naohiro Wada, Masami Shirai, Kozo Muto, Osamu Uemura, Yoshimitsu Goto, Naoya Fujita, Kazuhide Ohta, Masaki Shimizu, Koichi Tsukahara, Yukiko Mori, Hiroshi Akutagawa, Toshihiro Sawai, Kashiro Nishizawa, Akira Ashida, Naohisa Kawamura, Takuya Tanabe, Koji Taira, Seiji Kinoshita, Shinya Tanaka, Nobuhiko Shimizu, Katsuhisa Yamamoto, Shinichi Sumimoto, Koichi Nakanishi, Noriyuki Aoyagi, Seiji Iwahashi, Masakazu Miyawaki, Ritsuko Miyashita, Masamitsu Nishino, Daisuke Hata, Mikio Goto, Ryojiro Tanaka, Kandai Nozu, Hiroshi Kaito, Sakiko Konohana, Ichiro Kamioka, Masayuki Yamane, Katsuji Kuwakado, Shoji Kagami, Yuhei Ito, Yoshihiko Murakami, Jiro Iwamoto, Yoshitsugu Kaku, Kentaro Kamesaki, Ken Hatae, Hitoshi Nakazato, Yasushi Otsuka, Tomohiro Ichimaru, Tadashi Sato

Affiliations

¹ Department of Pediatrics, Wakayama Medical University, Wakayama City, Japan.
² Division for Clinical Trials, Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan.
³ Department of Biostatistics and Epidemiology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
⁴ Department of Health Policy, National Center for Child Health and Development, Tokyo, Japan.
⁵ Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
⁶ Department of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan.
⁷ Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
⁸ National Center for Child Health and Development, Tokyo, Japan.
⁹ Department of Biostatistics, School of Public Health, The University of Tokyo, Tokyo, Japan.

PMID: 25054775
PMCID: PMC4284810
DOI: 10.1038/ki.2014.260

Abstract

In this multicenter, open-label, randomized controlled trial, we determined whether 2-month prednisolone therapy for steroid-sensitive nephrotic syndrome was inferior or not to 6-month therapy despite significantly less steroid exposure. The primary end point was time from start of initial treatment to start of frequently relapsing nephrotic syndrome. The pre-specified non-inferiority margin was a hazard ratio of 1.3 with one-sided significance of 5%. We randomly assigned 255 children with an initial episode of steroid-sensitive nephrotic syndrome to either 2 - or 6-month treatment of which 246 were eligible for final analysis. The total prednisolone exposure counted both initial and relapse prednisolone treatment administered over 24 months. Median follow-up in months was 36.7 in the 2-month and 38.2 in the 6-month treatment group. Time to frequent relaps was similar in both groups; however, the median was reached only in the 6-month group (799 days). The hazard ratio was 0.86 (90% confidence interval, 0.64-1.16) and met the non-inferior margin. Time to first relapse was also similar in both groups: median day 242 (2-month) and 243 (6-month). Frequency and severity of adverse events were similar in both groups. Most adverse events were transient and occurred during initial or relapse therapy. Thus, 2 months of initial prednisolone therapy for steroid-sensitive nephrotic syndrome, despite less prednisolone exposure, is not inferior to 6 months of initial therapy in terms of time to onset of frequently relapsing nephrotic syndrome.

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Figures

**Figure 2**
**Kaplan–Meier estimates of time to frequently relapsing nephrotic syndrome (FRNS).** HR, hazard ratio.

**Figure 3**
**Kaplan–Meier estimates of time to first relapse.** HR, hazard ratio.

**Figure 4**
**Initial treatment regimens.** Upper doses are in mg/m² per day. Maximum doses are in mg/day. D, daily; AD, alternate days.

**Figure 5**
**Treatment regimens for relapse.** ^aUntil urinary protein is negative on 3 consecutive days using a urine dipstick test. Upper doses are in mg/m²/day. A maximum dose of each is the same as initial treatments in Figure 4. AD, alternate days; D, daily.

See this image and copyright information in PMC

Comment in

Is two month initial prednisolone treatment for nephrotic syndrome inferior to longer duration therapy?
Sinha A, Bagga A, Iyengar A, Mathew JL. Sinha A, et al. Indian Pediatr. 2014 Oct;51(10):811-7. doi: 10.1007/s13312-014-0508-7. Indian Pediatr. 2014. PMID: 25362013 No abstract available.
New lessons from randomized trials in steroid-sensitive nephrotic syndrome: clear evidence against long steroid therapy.
Hoyer PF. Hoyer PF. Kidney Int. 2015 Jan;87(1):17-9. doi: 10.1038/ki.2014.354. Kidney Int. 2015. PMID: 25549122
Re "How postoperative respiratory distress conspired with friendly fire to kill 'Stonewall' Jackson".
Crymes WB Jr. Crymes WB Jr. Pharos Alpha Omega Alpha Honor Med Soc. 2015 Spring;78(2):46. Pharos Alpha Omega Alpha Honor Med Soc. 2015. PMID: 26043525 No abstract available.

References

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1. van Husen M, Kemper MJ. New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol. 2011;26:881–892. - PubMed
1. Tarshish P, Tobin JN, Bernstein J, et al. Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children. J Am Soc Nephrol. 1997;8:769–776. - PubMed
1. Ueda N, Chihara M, Kawaguchi S, et al. Intermittent versus long-term tapering prednisolone for initial therapy in children with idiopathic nephrotic syndrome. J Pediatr. 1988;112:122–126. - PubMed
1. Ehrich JH, Brodehl J. Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft für Pädiatrische Nephrologie. Eur J Pediatr. 1993;152:357–361. - PubMed

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A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment

Collaborators

Affiliations

A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment

Authors

Collaborators

Affiliations

Abstract

Figures

Comment in

References

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MeSH terms

Substances

Associated data

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Full Text Sources

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Medical

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