Abstract
Background
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.
Methods
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.
Results
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.
Conclusion
Rituximab treatment was effective not only in childhood-onset but also in adult-onset SDNS. Further studies are needed to establish optimal treatment regimens.
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References
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.
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.
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.
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.
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.
Iijima K, Sako M, Nozu K. Rituximab for nephrotic syndrome in children. Clin Exp Nephrol. 2017;21:193–202.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Acknowledgements
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.
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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.
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Katsuno, T., Masuda, T., Saito, S. et al. Therapeutic efficacy of rituximab for the management of adult-onset steroid-dependent nephrotic syndrome: a retrospective study. Clin Exp Nephrol 23, 207–214 (2019). https://doi.org/10.1007/s10157-018-1630-y
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DOI: https://doi.org/10.1007/s10157-018-1630-y