Koichi Kamei1, Kenji Ishikura2, Mayumi Sako3, Kunihiko Aya4, Ryojiro Tanaka5, Kandai Nozu6, Hiroshi Kaito6, Koichi Nakanishi7, Yoshiyuki Ohtomo8, Kenichiro Miura9, Shori Takahashi10, Tetsuji Morimoto11, Wataru Kubota12, Shuichi Ito13, Hidefumi Nakamura14, Kazumoto Iijima6. 1. Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan. kamei-k@ncchd.go.jp. 2. Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan. 3. 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. 4. Department of Pediatrics, Kurashiki Central Hospital, 1-1-1, Miwa, Kurashiki, Okayama, 710-8602, Japan. 5. Department of Nephrology, Hyogo Prefectural Kobe Children's Hospital, 1-6-7, Minamimachi, Minatojima, Chuo-ku, Kobe, Hyogo, 650-0047, Japan. 6. Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan. 7. Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, 207, Azauehara, Nishihara-cho, Nakagami-gun, Okinawa, 903-0215, Japan. 8. Department of Pediatrics, Juntendo University Nerima Hospital, 3-1-10, Takanodai, Nerima-ku, Tokyo, 177-8521, Japan. 9. Department of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. 10. Department of Pediatrics, Nihon University Itabashi Hospital, 30-1, Oyaguchikamimachi, Itabashi-ku, Tokyo, 173-8610, Japan. 11. Division of Pediatrics, Tohoku Medical and Pharmaceutical University Hospital, 1-12-1, Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8512, Japan. 12. Department of Nephrology, Tokyo Metropolitan Children's Medical Center, 2-8-29, Musashidai, Fuchu, Tokyo, 183-8561, Japan. 13. Department of Pediatrics, Graduate School of Medicine, Yokohama City University, 3-9, Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan. 14. Department of Development Strategy, Center for Clinical Research and Development, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
Abstract
BACKGROUND: Although rituximab effectively prevents relapses of complicated frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS), data of long-term outcomes and safety are limited. METHODS:Fifty-one patients (age, 3-38 years) with childhood-onset complicated FRNS or SDNS, who received rituximab in investigator-initiated multicenter prospective trials were enrolled. Rituximab was administered at 375 mg/m2 once weekly for 4 weeks, and immunosuppressive agents were discontinued according to the study protocol. We investigated relapses, re-administration of immunosuppressive agents, additional rituximab treatment, body height, renal function, and late adverse events during the observation period. RESULTS: Forty-eight patients (94%) developed relapses during the observation period (median, 59 months) and the 50% relapse-free survival was 261 days. Thirty patients (59%) developed SDNS, 44 (86%) required re-administration of immunosuppressive agents, and 22 (43%) receivedadditional rituximab treatment. All patients who were receiving immunosuppressive agents at rituximab treatment required eitherimmunosuppressive agents or additional rituximab treatment. On the contrary, 5 of the 13 patients without immunosuppressive agents at rituximab treatment required neither immunosuppressive agents nor additional rituximab treatment and 3 of them did not develop relapse during observation period. Growth failure due to steroid toxicity did not progress and none of the patients developed chronic renal insufficiency. None of the patients suffered from rituximab-related late adverse events. CONCLUSIONS: As most patients suffer from relapses after B-cell recovery, long-term immunosuppressive agents or additional rituximab treatment is necessary. However, some patients who can discontinue immunosuppressive agents before rituximab treatment may achieve long-term remission after rituximab treatment without immunosuppressive agents.
RCT Entities:
BACKGROUND: Although rituximab effectively prevents relapses of complicated frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS), data of long-term outcomes and safety are limited. METHODS: Fifty-one patients (age, 3-38 years) with childhood-onset complicated FRNS or SDNS, who received rituximab in investigator-initiated multicenter prospective trials were enrolled. Rituximab was administered at 375 mg/m2 once weekly for 4 weeks, and immunosuppressive agents were discontinued according to the study protocol. We investigated relapses, re-administration of immunosuppressive agents, additional rituximab treatment, body height, renal function, and late adverse events during the observation period. RESULTS: Forty-eight patients (94%) developed relapses during the observation period (median, 59 months) and the 50% relapse-free survival was 261 days. Thirty patients (59%) developed SDNS, 44 (86%) required re-administration of immunosuppressive agents, and 22 (43%) received additional rituximab treatment. All patients who were receiving immunosuppressive agents at rituximab treatment required either immunosuppressive agents or additional rituximab treatment. On the contrary, 5 of the 13 patients without immunosuppressive agents at rituximab treatment required neither immunosuppressive agents nor additional rituximab treatment and 3 of them did not develop relapse during observation period. Growth failure due to steroidtoxicity did not progress and none of the patients developed chronic renal insufficiency. None of the patients suffered from rituximab-related late adverse events. CONCLUSIONS: As most patients suffer from relapses after B-cell recovery, long-term immunosuppressive agents or additional rituximab treatment is necessary. However, some patients who can discontinue immunosuppressive agents before rituximab treatment may achieve long-term remission after rituximab treatment without immunosuppressive agents.
Authors: Markus J Kemper; Jutta Gellermann; Sandra Habbig; Rafael T Krmar; Katalin Dittrich; Therese Jungraithmayr; Lars Pape; Ludwig Patzer; Heiko Billing; Lutz Weber; Martin Pohl; Katrin Rosenthal; Anne Rosahl; Dirk E Mueller-Wiefel; Jörg Dötsch Journal: Nephrol Dial Transplant Date: 2011-11-09 Impact factor: 5.992
Authors: Piero Ruggenenti; Barbara Ruggiero; Paolo Cravedi; Marina Vivarelli; Laura Massella; Maddalena Marasà; Antonietta Chianca; Nadia Rubis; Bogdan Ene-Iordache; Michael Rudnicki; Rosa Maria Pollastro; Giovambattista Capasso; Antonio Pisani; Marco Pennesi; Francesco Emma; Giuseppe Remuzzi Journal: J Am Soc Nephrol Date: 2014-01-30 Impact factor: 10.121