Ryohei Yamamoto1,2, Enyu Imai3, Shoichi Maruyama4, Hitoshi Yokoyama5, Hitoshi Sugiyama6, Asami Takeda7, Tatsuo Tsukamoto8, Shunya Uchida9, Kazuhiko Tsuruya10, Tatsuya Shoji11, Hiroki Hayashi12, Yasuhiro Akai13, Megumu Fukunaga14, Tsuneo Konta15, Saori Nishio16, Shunsuke Goto17, Hirofumi Tamai18, Kojiro Nagai19, Ritsuko Katafuchi20, Kosuke Masutani21, Takashi Wada22, Tomoya Nishino23, Arimasa Shirasaki24, Hiroshi Sobajima25, Kosaku Nitta26, Kunihiro Yamagata27, Junichiro J Kazama28, Keiju Hiromura29, Hideo Yasuda30, Makoto Mizutani31, Toshiyuki Akahori32, Tomohiko Naruse33, Takeyuki Hiramatsu34, Kunio Morozumi35, Tetsushi Mimura36, Yosuke Saka37, Eiji Ishimura38, Hajime Hasegawa39, Daisuke Ichikawa40, Takashi Shigematsu41, Hiroshi Sato42, Ichiei Narita43, Yoshitaka Isaka44. 1. Health and Counseling Center, Osaka University, 1-17 Machikaneyama-cho, Toyonaka, Osaka, 560-0043, Japan. yamamoto.ryohei.ras@osaka-u.ac.jp. 2. Department of Nephrology, Osaka University Graduate School of Medicine, 2-2-D11 Yamadaoka, Suita, Osaka, 565-0871, Japan. yamamoto.ryohei.ras@osaka-u.ac.jp. 3. Nakayamadera Imai Clinic, 2-8-18 Nakayamadera, Takarazuka, Hyogo, 665-0861, Japan. 4. Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan. 5. Department of Nephrology, Kanazawa Medical University School of Medicine, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan. 6. Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kita-ku, Okayama, Okayama, 700-8558, Japan. 7. Kidney Disease Center, Japanese Red Cross Nagoya Daini Hospital, 2-9 Myokencho, Showa-ku, Nagoya, Aichi, 466-8650, Japan. 8. Department of Nephrology and Dialysis, Kitano Hospital, Tazuke Kofukai Medical Research Institute, 2-4-20 Ogimachi, Kita-ku, Osaka, Osaka, 530-8480, Japan. 9. Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8606, Japan. 10. Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan. 11. Department of Kidney Disease and Hypertension, Osaka General Medical Center, 3-1-56 Bandaihigashi, Sumiyoshi-ku, Osaka, Osaka, 558-8558, Japan. 12. Department of Nephrology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan. 13. First Department of Internal Medicine, Nara Medical University, 840 Shijocho, Kashihara, Nara, 634-8522, Japan. 14. Division of Nephrology, Department of Internal Medicine, Toyonaka Municipal Hospital, 4-14-1 Shibaharacho, Toyonaka, Osaka, 560-8565, Japan. 15. Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2 Iida-Nishi, Yamagata-shi, Yamagata, Yamagata, 990-9585, Japan. 16. Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. 17. Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan. 18. Department of Nephrology, Anjo Kosei Hospital, 28 Higashihirokute, Anjocho, Anjo, Aichi, 446-8602, Japan. 19. Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan. 20. Kidney Unit, National Hospital Organization Fukuokahigashi Medical Center, 1-1-1 Chidori, Koga, Fukuoka, 811-3195, Japan. 21. Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, Fukuoka, 814-0180, Japan. 22. Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan. 23. Department of Nephrology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan. 24. Department of Nephrology, Ichinomiya Municipal Hospital, 2-2-22 Bunkyo, Ichinomiya, Aichi, 491-8558, Japan. 25. Department of Diabetology and Nephrology, Ogaki Municipal Hospital, 4-86 Minaminokawacho, Ogaki, Gifu, 503-8502, Japan. 26. Department of Nephrology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. 27. Department of Nephrology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. 28. Department of Nephrology and Hypertension, Fukushima Medical University School of Medicine, 1 Hikariga-oka, Fukushima-City, Fukushima, 960-1295, Japan. 29. Department of Nephrology and Rheumatology, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan. 30. Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan. 31. Department of Nephrology, Handa City Hospital, 2-29 Toyocho, Handa, Aichi, 475-8599, Japan. 32. Department of Nephrology, Chutoen General Medical Center, 1-1 Shobugaike, Kakegawa, Shizuoka, 436-8555, Japan. 33. Department of Nephrology, Kasugai Municipal Hospital, 1-1-1 Takakicho, Kasugai, Aichi, 486-8510, Japan. 34. Department of Nephrology, Konan Kosei Hospital, 137 Omatsubara, Takayacho, Konan, Aichi, 483-8704, Japan. 35. Department of Nephrology, Masuko Memorial Hospital, 35-28 Takebashicho, Nakamura-ku, Nagoya, Aichi, 453-8566, Japan. 36. Department of Nephrology, Gifu Prefectural Tajimi Hospital, 5-161 Maebatacho, Tajimi, Gifu, 507-8522, Japan. 37. Department of Nephrology, Yokkaichi Municipal Hospital, 2-2-37 Shibata, Yokkaichi, Mie, 510-8567, Japan. 38. Department of Nephrology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan. 39. Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-850, Japan. 40. Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-000, Japan. 41. Department of Nephrology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-City, Wakayama, 641-8509, Japan. 42. Department of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi, 980-8574, Japan. 43. Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, 757 Ichibancho, Asahimachi-dori, Chuo Ward, Niigata, Niigata, 951-8510, Japan. 44. Department of Nephrology, Osaka University Graduate School of Medicine, 2-2-D11 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Abstract
BACKGROUND: Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse. METHODS: This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors. RESULTS: Remission was observed at 3-7, 8-14, 15-21, 22-28, and 30-56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3-7, 8-14, 15-21, 22-28, 30-56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively). CONCLUSION: The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients.
BACKGROUND: Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse. METHODS: This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors. RESULTS: Remission was observed at 3-7, 8-14, 15-21, 22-28, and 30-56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3-7, 8-14, 15-21, 22-28, 30-56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively). CONCLUSION: The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients.
Authors: Hajeong Lee; Kyung Don Yoo; Yun Kyu Oh; Dong Ki Kim; Kook-Hwan Oh; Kwon Wook Joo; Yon Su Kim; Curie Ahn; Jin Suk Han; Chun Soo Lim Journal: Medicine (Baltimore) Date: 2016-03 Impact factor: 1.889