Clinical and Experimental Nephrology

, Volume 23, Issue 2, pp 207–214 | Cite as

Therapeutic efficacy of rituximab for the management of adult-onset steroid-dependent nephrotic syndrome: a retrospective study

  • Takayuki KatsunoEmail author
  • Tomohiro Masuda
  • Shoji Saito
  • Noritoshi Kato
  • Takuji Ishimoto
  • Sawako Kato
  • Tomoki Kosugi
  • Naotake Tsuboi
  • Hiroshi Kitamura
  • Toyonori Tsuzuki
  • Yasuhiko Ito
  • Shoichi Maruyama
Original article



Recent reports have described the efficacy of rituximab in treating steroid-dependent nephrotic syndrome (SDNS) in pediatric patients. However, few reports describe data regarding adult-onset SDNS. We investigated the efficacy of rituximab for the management of adult-onset SDNS.


We performed a retrospective cohort study investigating eight patients with adult-onset SDNS who were treated with rituximab. Clinical data were obtained at the initiation of rituximab therapy. The primary outcomes evaluated were successful suppression of relapses and CD19+ cells after rituximab treatment. The corticosteroid- and immunosuppressant-sparing effect and adverse events were additionally evaluated.


All eight patients were diagnosed with minimal change nephrotic syndrome and received immunosuppressants in addition to corticosteroid. Total number of relapses was 10.5 times as a median value. Rituximab administration was repeated in two patients, whereas six received single-dose rituximab. Three of eight (37.5%) patients showed relapse after rituximab therapy. A rituximab-induced depletion in CD19+ cells noted initially was followed by their reappearance in all patients. There were cases with no relapse after the reappearance of CD19+ cells. The median relapse time pre- and post-rituximab therapy showed a decrease from 1 time/year (interquartile range [IQR] 1–3 times/year) to 0 time/year (IQR 0–1 time/year). Rituximab treatment induced a significant reduction in the required doses of corticosteroid and cyclosporine (P < 0.01). No serious adverse events were observed.


Rituximab treatment was effective not only in childhood-onset but also in adult-onset SDNS. Further studies are needed to establish optimal treatment regimens.


Adult-onset Steroid-dependent nephrotic syndrome Frequently relapsing nephrotic syndrome Minimal change nephrotic syndrome Rituximab 



This study was supported partly by a Grant-in-Aid for Progressive Renal Diseases Research, and Research on Rare and Intractable Disease, from the Ministry of Health, Labour and Welfare of Japan.

Compliance with ethical standards

Conflict of interest

The Department of Nephrology and Rheumatology, Aichi Medical University received research promotion grants from Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Co., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Limited., and Torii Pharmaceutical Co., Ltd. The Department of Nephrology, Nagoya University Graduate School of Medicine received research promotion grants from Astellas Pharma Inc., Bristol-Myers Squibb., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical Co., Ltd., MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Limited., Torii Pharmaceutical Co., Ltd., and Sumitomo Dainippon Pharma Co., Ltd.

Human and animal rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of The Ethics Committee for Human Research of Nagoya University Hospital at which the studies were conducted (IRB approval number 2017-0192) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

The Ethical Committee approved this retrospective cohort study without written informed consent from patients; however, informed consent was obtained from most patients at the time of performing a renal biopsy.


  1. 1.
    Fujimoto S, Yamamoto Y, Hisanaga S, Morita S, Eto T, Tanaka K. Minimal change nephrotic syndrome in adults: response to corticosteroid therapy and frequency of relapse. Am J Kidney Dis. 1991;17:687–92.CrossRefGoogle Scholar
  2. 2.
    Nakayama M, Katafuchi R, Yanase T, Ikeda K, Tanaka H, Fujimi S. Steroid responsiveness and frequency of relapse in adult-onset minimal change nephrotic syndrome. Am J Kidney Dis. 2002;39:503–12.CrossRefGoogle Scholar
  3. 3.
    Sato M, Takei T, Moriyama T, Itabashi M, Nitta K. Long-term outcomes of initial therapy for idiopathic membranous nephropathy. Clin Exp Nephrol. 2017;21:842–51.CrossRefGoogle Scholar
  4. 4.
    Ruggenenti P, Cravedi P, Chianca A, Perna A, Ruggiero B, Gaspari F, et al. Rituximab in idiopathic membranous nephropathy. J Am Soc Nephrol. 2012;23:1416–25.CrossRefGoogle Scholar
  5. 5.
    Katsuno T, Ozaki T, Kim H, Kato N, Suzuki Y, Akiyama S, et al. Single-dose rituximab therapy for refractory idiopathic membranous nephropathy: a single-center experience. Intern Med. 2017;56:1679–86.CrossRefGoogle Scholar
  6. 6.
    Iijima K, Sako M, Nozu K. Rituximab for nephrotic syndrome in children. Clin Exp Nephrol. 2017;21:193–202.CrossRefGoogle Scholar
  7. 7.
    Benz K, Dötsch J, Rascher W, Stachel D. Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy. Pediatr Nephrol. 2004;19:794–7.CrossRefGoogle Scholar
  8. 8.
    Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, et al. Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol. 2008;23:1269–79.CrossRefGoogle Scholar
  9. 9.
    Kamei K, Ito S, Nozu K, Fujinaga S, Nakayama M, Sako M, et al. Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children. Pediatr Nephrol. 2009;24:1321–8.CrossRefGoogle Scholar
  10. 10.
    Sellier-Leclerc AL, Macher MA, Loirat C, Guérin V, Watier H, Peuchmaur M, et al. Rituximab efficiency in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol. 2010;25:1109–15.CrossRefGoogle Scholar
  11. 11.
    Kemper MJ, Gellermann J, Habbig S, Krmar RT, Dittrich K, Jungraithmayr T, et al. Long-term follow-up after rituximab for steroid-dependent idiopathic nephrotic syndrome. Nephrol Dial Transplant. 2012;27:1910–5.CrossRefGoogle Scholar
  12. 12.
    Ravani P, Magnasco A, Edefonti A, Murer L, Rossi R, Ghio L, et al. Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: a randomized controlled trial. Clin J Am Soc Nephrol. 2011;6:1308–15.CrossRefGoogle Scholar
  13. 13.
    Ravani P, Rossi R, Bonanni A, Quinn RR, Sica F, Bodria M, et al. Rituximab in children with steroid-dependent nephrotic syndrome: a multicenter, open-label, noninferiority, randomized controlled trial. J Am Soc Nephrol. 2015;26:2259–66.CrossRefGoogle Scholar
  14. 14.
    Iijima K, Sako M, Nozu K, Mori R, Tuchida N, Kamei K, et al. Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2014;384:1273–81.CrossRefGoogle Scholar
  15. 15.
    Munyentwali H, Bouachi K, Audard V, Remy P, Lang P, Mojaat R, et al. Rituximab is an efficient and safe treatment in adults with steroid-dependent minimal change disease. Kidney Int. 2013;83:511–6.CrossRefGoogle Scholar
  16. 16.
    Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasà M, et al. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol. 2014;25:850–63.CrossRefGoogle Scholar
  17. 17.
    Iwabuchi Y, Takei T, Moriyama T, Itabashi M, Nitta K. Long-term prognosis of adult patients with steroid-dependent minimal change nephrotic syndrome following rituximab treatment. Medicine (Baltim). 2014;93:e300.CrossRefGoogle Scholar
  18. 18.
    Guitard J, Hebral AL, Fakhouri F, Joly D, Daugas E, Rivalan J, et al. Rituximab for minimal-change nephrotic syndrome in adulthood: predictive factors for response, long-term outcomes and tolerance. Nephrol Dial Transplant. 2014;29:2084–91.CrossRefGoogle Scholar
  19. 19.
    Bruchfeld A, Benedek S, Hilderman M, Medin C, Snaedal-Jonsdottir S, Korkeila M. Rituximab for minimal change disease in adults: long-term follow-up. Nephrol Dial Transplant. 2014;29:851–6.CrossRefGoogle Scholar
  20. 20.
    Takei T, Itabashi M, Moriyama T, Kojima C, Shiohira S, Shimizu A, et al. Effect of single-dose rituximab on steroid-dependent minimal-change nephrotic syndrome in adults. Nephrol Dial Transplant. 2013;28:1225–32.CrossRefGoogle Scholar
  21. 21.
    Nishi S, Ubara Y, Utsunomiya Y, Okada K, Obata Y, Kai H, et al. Evidence-based clinical practice guidelines for nephrotic syndrome 2014. Clin Exp Nephrol. 2016;20:342–70.CrossRefGoogle Scholar
  22. 22.
    Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.CrossRefGoogle Scholar
  23. 23.
    van den Berg JG, Weening JJ. Role of the immune system in the pathogenesis of idiopathic nephrotic syndrome. Clin Sci (Lond). 2004;107:125–36.CrossRefGoogle Scholar
  24. 24.
    Fornoni A, Sageshima J, Wei C, Merscher-Gomez S, Aguillon-Prada R, Jauregui AN, et al. Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis. Sci Transl Med. 2011;3:85ra46.CrossRefGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2018

Authors and Affiliations

  • Takayuki Katsuno
    • 1
    • 2
    Email author
  • Tomohiro Masuda
    • 2
  • Shoji Saito
    • 2
  • Noritoshi Kato
    • 2
  • Takuji Ishimoto
    • 2
  • Sawako Kato
    • 2
  • Tomoki Kosugi
    • 2
  • Naotake Tsuboi
    • 2
  • Hiroshi Kitamura
    • 3
  • Toyonori Tsuzuki
    • 4
  • Yasuhiko Ito
    • 1
  • Shoichi Maruyama
    • 2
  1. 1.Department of Nephrology and RheumatologyAichi Medical UniversityNagakuteJapan
  2. 2.Department of NephrologyNagoya University Graduate School of MedicineNagoyaJapan
  3. 3.Department of PathologyNational Hospital Organization Chiba East HospitalChibaJapan
  4. 4.Department of Surgical PathologyAichi Medical UniversityNagakuteJapan

Personalised recommendations