Single dose of rituximab in children with steroid-dependent minimal change nephrotic syndrome

Niu,Xiao-Ling; Hao,Sheng; Wang,Ping; Zhang,Wei; Guo,Gui-Mei; Wu,Ying; Kuang,Xin-Yu; Zhu,Guang-Hua; Huang,Wen-Yan

doi:10.3892/br.2016.711

Single dose of rituximab in children with steroid-dependent minimal change nephrotic syndrome

Authors:
- Xiao-Ling Niu
- Sheng Hao
- Ping Wang
- Wei Zhang
- Gui-Mei Guo
- Ying Wu
- Xin-Yu Kuang
- Guang-Hua Zhu
- Wen-Yan Huang
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Affiliations: Department of Nephrology and Rheumatology, Children's Hospital of Shanghai, Shanghai Jiaotong University, Shanghai 200062, P.R. China
Published online on: June 30, 2016 https://doi.org/10.3892/br.2016.711
Pages: 237-242

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Abstract

Rituximab (RTX) can be used in children with nephrotic syndrome, particularly in those with steroid-dependent nephrotic syndrome (SDNS). However, at present there is no unified standard of how to use RTX, with regard to the amount of doses and frequency, in children with nephrotic syndrome. The study aimed to investigate the therapeutic efficacy of a single dose of RTX in children with steroid‑dependent minimal change nephrotic syndrome (SD-MCNS). The patients with biopsy‑proven minimal change disease (MCD) and clinical features of SDNS received a single dose of RTX (375 mg/m2). The toxicity and side effects of RTX were also observed. The study included 19 patients (10 males and 9 females). Follow-up of the patients was 1-50 months (28.1±16.6 months). B-cell depletion was achieved with RTX infusion (CD20<0.5%) and lasted 1‑6 months (mean, 2.92±1.57 months). During follow‑up, 10 patients remained in complete remission and did not relapse without administration of oral steroids or immunosuppressants for 4-50 months (mean, 30.1±12.6 months), despite recovery of the B-cell count. Nine patients relapsed in the process of reducing steroids, thus, treatment was maintained at a lower dosage (T=0, P<0.05) than prior to use of RTX. The number of relapses also decreased significantly (T=95, P<0.05). Five of the patients relapsed after stopping steroid for several months. At the end of follow-up, the efficacy of a single induction of RTX was 47.4% (9/19). There were no significant side effects associated with administration of RTX. In conclusion, RTX is a safe and effective alternative for children with SD-MCNS. RTX is an effective treatment for the rapid induction of remission and reduces relapse and steroid dependency. A single dose of RTX for children with SD-MCNS is recommended for rapid induction of remission, reduction of long‑term steroid dosage, and decrease in the number of relapses, as it has few side effects.

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1	McKinney PA, Feltbower RG, Brocklebank JT and Fitzpatrick MM: Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire, UK. Pediatr Nephrol. 16:1040–1044. 2001. View Article : Google Scholar : PubMed/NCBI
2	Tarshish P, Tobin JN, Bernstein J and Edelmann CM Jr: 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. 8:769–776. 1997.PubMed/NCBI
3	Hodson EM, Willis NS and Craig JC: Non-corticosteroid treatment for nephrotic syndrome in children. Cochrane Database Syst Rev. 1:CD0022902008.PubMed/NCBI
4	Tokunaga M, Saito K, Kawabata D, Imura Y, Fujii T, Nakayamada S, Tsujimura S, Nawata M, Iwata S, Azuma T, et al: Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann Rheum Dis. 66:470–475. 2007. View Article : Google Scholar : PubMed/NCBI
5	Iijima K: Rituximab for childhood refractory nephrotic syndrome. Pediatr Int. 53:617–621. 2011. View Article : Google Scholar : PubMed/NCBI
6	Ravani P, Ponticelli A, Siciliano C, Fornoni A, Magnasco A, Sica F, Bodria M, Caridi G, Wei C, Belingheri M, et al: Rituximab is a safe and effective long-term treatment for children with steroid and calcineurin inhibitor-dependent idiopathic nephrotic syndrome. Kidney Int. 84:1025–1033. 2013. View Article : Google Scholar : PubMed/NCBI
7	Kamei K, Ito S, Nozu K, Fujinaga S, Nakayama M, Sako M, Saito M, Yoneko M and Iijima K: Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children. Pediatr Nephrol. 24:1321–1328. 2009. View Article : Google Scholar : PubMed/NCBI
8	Gulati A, Sinha A, Jordan SC, Hari P, Dinda AK, Sharma S, Srivastava RN, Moudgil A and Bagga A: Efficacy and safety of treatment with rituximab for difficult steroid-resistant and -dependent nephrotic syndrome: Multicentric report. Clin J Am Soc Nephrol. 5:2207–2212. 2010. View Article : Google Scholar : PubMed/NCBI
9	Iijima K, Sako M, Nozu K, Mori R, Tuchida N, Kamei K, Miura K, Aya K, Nakanishi K, Ohtomo Y, et al: Rituximab for Childhood-onset Refractory Nephrotic Syndrome (RCRNS) Study Group: Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 384:1273–1281. 2014. View Article : Google Scholar : PubMed/NCBI
10	Fujinaga S, Hirano D, Nishizaki N, Kamei K, Ito S, Ohtomo Y, Shimizu T and Kaneko K: Single infusion of rituximab for persistent steroid-dependent minimal-change nephrotic syndrome after long-term cyclosporine. Pediatr Nephrol. 25:539–544. 2010. View Article : Google Scholar : PubMed/NCBI
11	Kidney Disease Improving Global Outcomes: KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int Suppl. 2:139–274. 2012.
12	Schulman SL, Kaiser BA, Polinsky MS, Srinivasan R and Baluarte HJ: Predicting the response to cytotoxic therapy for childhood nephrotic syndrome: superiority of response to corticosteroid therapy over histopathologic patterns. J Pediatr. 113:996–1001. 1988. View Article : Google Scholar : PubMed/NCBI
13	Prytuła A, Iijima K, Kamei K, Geary D, Gottlich E, Majeed A, Taylor M, Marks SD, Tuchman S, Camilla R, et al: Rituximab in refractory nephrotic syndrome. Pediatr Nephrol. 25:461–468. 2010. View Article : Google Scholar : PubMed/NCBI
14	Sun L, Xu H, Shen Q, Cao Q, Rao J, Liu HM, Fang XY and Zhou LJ: Efficacy of rituximab therapy in children with refractory nephrotic syndrome: a prospective observational study in Shanghai. World J Pediatr. 10:59–63. 2014. View Article : Google Scholar : PubMed/NCBI
15	Ito S, Kamei K, Ogura M, Udagawa T, Fujinaga S, Saito M, Sako M and Iijima K: Survey of rituximab treatment for childhood-onset refractory nephrotic syndrome. Pediatr Nephrol. 28:257–264. 2013. View Article : Google Scholar : PubMed/NCBI
16	Tellier S, Brochard K, Garnier A, Bandin F, Llanas B, Guigonis V, Cailliez M, Pietrement C, Dunand O, Nathanson S, et al: Long-term outcome of children treated with rituximab for idiopathic nephrotic syndrome. Pediatr Nephrol. 28:911–918. 2013. View Article : Google Scholar : PubMed/NCBI
17	Sellier-Leclerc AL, Baudouin V, Kwon T, Macher MA, Guérin V, Lapillonne H, Deschênes G and Ulinski T: Rituximab in steroid-dependent idiopathic nephrotic syndrome in childhood - follow-up after CD19 recovery. Nephrol Dial Transplant. 27:1083–1089. 2012. View Article : Google Scholar : PubMed/NCBI
18	Kemper MJ, Gellermann J, Habbig S, Krmar RT, Dittrich K, Jungraithmayr T, Pape L, Patzer L, Billing H, Weber L, et al: Long-term follow-up after rituximab for steroid-dependent idiopathic nephrotic syndrome. Nephrol Dial Transplant. 27:1910–1915. 2012. View Article : Google Scholar : PubMed/NCBI
19	Ravani P, Magnasco A, Edefonti A, Murer L, Rossi R, Ghio L, Benetti E, Scozzola F, Pasini A, Dallera N, 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. 6:1308–1315. 2011. View Article : Google Scholar : PubMed/NCBI
20	Sellier-Leclerc AL, Macher MA, Loirat C, Guérin V, Watier H, Peuchmaur M, Baudouin V and Deschênes G: Rituximab efficiency in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol. 25:1109–1115. 2010. View Article : Google Scholar : PubMed/NCBI
21	El-Reshaid K, Sallam HT, Hakim AA, Al-Attiyah R and EI-Reshaid K: Rituximab in treatment of idiopathic glomerulopathy. Saudi J Kidney Dis Transpl. 23:973–978. 2012. View Article : Google Scholar : PubMed/NCBI
22	Samarghitean C, Väliaho J and Vihinen M: Online registry of genetic and clinical immunodeficiency diagnostic laboratories, IDdiagnostics. J Clin Immunol. 24:53–61. 2004. View Article : Google Scholar : PubMed/NCBI
23	Kyrieleis HA, Löwik MM, Pronk I, Cruysberg HR, Kremer JA, Oyen WJ, van den Heuvel BL, Wetzels JF and Levtchenko EN: Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. Clin J Am Soc Nephrol. 4:1593–1600. 2009. View Article : Google Scholar : PubMed/NCBI
24	Kemper MJ, Meyer-Jark T, Lilova M and Müller-Wiefel DE: Combined T- and B-cell activation in childhood steroid-sensitive nephrotic syndrome. Clin Nephrol. 60:242–247. 2003. View Article : Google Scholar : PubMed/NCBI
25	Cho BS, Yoon SR, Jang JY, Pyun KH and Lee CE: Up-regulation of interleukin-4 and CD23/FcepsilonRII in minimal change nephrotic syndrome. Pediatr Nephrol. 13:199–204. 1999. View Article : Google Scholar : PubMed/NCBI
26	Kimata H, Fujimoto M and Furusho K: Involvement of interleukin (IL)-13, but not IL-4, in spontaneous IgE and IgG4 production in nephrotic syndrome. Eur J Immunol. 25:1497–1501. 1995. View Article : Google Scholar : PubMed/NCBI