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Rituximab therapy for refractory steroid-resistant nephrotic syndrome in children

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Abstract

Patients with steroid-resistant nephrotic syndrome (SRNS) who develop resistance to immunosuppressive agents, defined as refractory SRNS, have poor renal outcomes. Although the chimeric anti-CD20 monoclonal antibody rituximab has shown efficacy for frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome, its efficacy for refractory SRNS remains uncertain due to limited data. According to previous case reports, 50.4% of patients with refractory SRNS showed clinical improvements after rituximab treatment. Remission rates in patients with initial steroid resistance and late steroid resistance were 43.9 and 57.7%, respectively, and 41.5 and 63.6% in patients with focal segmental glomerulosclerosis and minor glomerular abnormalities, respectively. However, various factors (race, disease severity, number of rituximab doses, concomitant treatments, and observation period) differed among these observational studies and their consensus may also have been affected by potential publication bias. Rituximab monotherapy may have some degree of efficacy and lead to satisfactory outcomes in a subset of patients with refractory SRNS. However, administration of concomitant treatments during rituximab-mediated B cell depletion, such as methylprednisolone pulse therapy, daily oral prednisolone therapy, and immunosuppressive agents, may lead to better outcomes in these patients. Large-scale, multi-center prospective studies are needed to evaluate the efficacy and safety of such regimens.

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We thank Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

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  1. Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Koichi Kamei & Kenji Ishikura

  2. Division for Clinical Trials, Department of Clinical Research, Center for Clinical Research and Development, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Mayumi Sako

  3. Department of Pediatrics, Graduate School of Medicine, Yokohama City University, 3-9, Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan

    Shuichi Ito

  4. Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan

    Kandai Nozu & Kazumoto Iijima

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KK has received lecture fees from Chugai Pharmaceutical Co., Ltd. and AbbVie GK. KIs has received lecture fees from Asahi Kasei Pharma, Chugai Pharmaceutical Co., Ltd., Zenyaku Kogyo Co., Ltd., and Novartis Pharma K.K. and grants from Asahi Kasei Pharma, Chugai Pharmaceutical Co., Ltd., and NovartisPharma K.K. MS has received a consulting fee from Zenyaku Kogyo Co. Ltd. SI has received grants from AbbVie GK., Asahi kasei Pharma Corporation, Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., CSL Behring, Eisai Co. Ltd., Maruho Co. Ltd., Japan Blood Product Organization, Kyowa Hakko Kirin Co., Ltd., Phizer Co. Ltd. and Teijin Pharma Ltd. SI has received lecture fees and/or consultant fees from AbbVie LLC, Astellas Pharma Inc., Alexion Pharma LLC, Chugai Pharmaceutical Co., Ltd., Eisai Co. Ltd., Daiichi Sankyo, Co., Ltd., Novartis Pharma K.K., Japan Blood Product Organization, JCR Pharmaceuticals Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., Sanofi Genzyme Co. Ltd., Tanabe Mitsubishi Pharma, Novo Nordisk Pharma Ltd., Takeda Pharmaceutical Co., Ltd. and Zenyaku Kogyo Co. Ltd.. KN has received lecture fees from Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K. and Otsuka Pharmaceutical Co., Ltd. KIi has received grants from Novartis Pharma K.K., Japan Blood Product Organization, AbbVie LLC, JCR Pharmaceuticals Co., Ltd., Daiichi Sankyo, Co., Ltd., Teijin Pharma Ltd., CSL Behring, Novo Nordisk Pharma Ltd., Air Water Medical Inc., Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Eisai Co. Ltd.,Biofermin Pharmaceutical Co., Ltd., and Zenyaku Kogyo Co. Ltd., and lecture fees and/or consulting fees from Zenyaku Kogyo Co., Ltd., Novartis Pharma K.K., Chugai Pharmaceutical Co., Ltd., Astellas Pharma Inc., Springer Japan K.K., Meiji Seika Pharma Co., Ltd., Asahi kasei Pharma Corporation, Medical Review Co.,Ltd., Nippon Boehringer Ingelheim Co., Ltd., Baxter Limited, Ono Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho Co.,Ltd., Sanofi K.K., Alexion Pharma LLC., and Kyowa Hakko Kirin Co., Ltd.

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Kamei, K., Ishikura, K., Sako, M. et al. Rituximab therapy for refractory steroid-resistant nephrotic syndrome in children. Pediatr Nephrol 35, 17–24 (2020). https://doi.org/10.1007/s00467-018-4166-1

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