Febuxostat Therapy for Patients With Stage 3 CKD and Asymptomatic Hyperuricemia: A Randomized Trial  Kenjiro Kimura, Tatsuo Hosoya, Shunya Uchida, Masaaki Inaba, Hirofumi Makino, Shoichi Maruyama, Sadayoshi Ito, Tetsuya Yamamoto, Yasuhiko Tomino, Iwao Ohno, Yugo Shibagaki, Satoshi Iimuro, Naohiko Imai, Masanari Kuwabara, Hiroshi Hayakawa, Hiroshi Ohtsu, Yasuo Ohashi Kenjiro Kimura, Tatsuo Hosoya, Sadayoshi Ito, Masaaki Inaba, Yasuhiko Tomino, Shunya Uchida, Hirofumi Makino, Seiichi Matsuo, Hisashi Yamanaka, Tetsuya Yamamoto, Iwao Ohno, Yugo Shibagaki, Satoshi Iimuro, Naohiko Imai, Masanari Kuwabara, Hiroshi Hayakawa, Tadao Akizawa, MD, PhD, Tamio Teramoto, MD, PhD, Hiroshi Kasanuki, MD, PhD, Kenichi Yoshimura, PhD, Kenjiro Kimura, MD, PhD, Tatsuo Hosoya, MD, PhD, Yugo Shibagaki, MD, Iwao Ohno, MD, Hiroshi Sato, MD, Shunya Uchida, MD, Satoshi Horikoshi, MD, Syoichi Maruyama, MD, Masahiko Inaba, MD, Yuji Moriwaki, MD, Haruhito Uchida, MD, Nagayuki Kaneshiro, MD, Naohiko Imai, MD, Hidekazu Moriya, MD, Yasuhiro Komatsu, MD, Shinya Kaname, MD, Kazunari Hanaoka, MD, Makoto Ogura, MD, Masato Ikeda, MD, Kenji Kasai, MD, Akira Sugiura, MD, Kazushi Takahashi, MD, Kenichiro Kojima, MD, Kosaku Nitta, MD, Hirofumi Tamai, MD, Hiroshi Nagaya, MD, Senji Okuno, MD, Ryusuke Kakiya, MD, Hiroya Takeoka, MD, Kyouji Hirata, MD, Kenichiro Asano, MD, Yasuo Fukaya, MD, Yasushi Iwaida, MD, Yasuo Tsuneda, MD, Shigeaki Nishimura, MD, Takeyuki Hiramatsu, MD, Yoshitaka Isaka, MD, Takafumi Ito, MD, Yukio Yuzawa, MD, Kunihiro Yamagata, MD, Tadashi Sofue, MD, Yoshimi Jinguji, MD, Keita Hirano, MD, Kazuhiro Matsuyama, MD, Teruhiko Mizumoto, MD, Yuko Shibuya, MD, Masahiro Sugawara, MD, Moritoshi Kadomura, MD, Yasuaki Teshima, MD, Hiroshi Ohtani, MD, Hiroki Kamata, MD, Susumu Okawara, MD, Masaki Fukushima, MD, Katsumi Takemura, MD, Eriko Kinugasa, MD, Masami Kogure, MD, Yoichi Ehara, MD Kenjiro Kimura, Tatsuo Hosoya, Shunya Uchida, Masaaki Inaba, Hirofumi Makino, Shoichi Maruyama, Sadayoshi Ito, Tetsuya Yamamoto, Yasuhiko Tomino, Iwao Ohno, Yugo Shibagaki, Satoshi Iimuro, Naohiko Imai, Masanari Kuwabara, Hiroshi Hayakawa, Hiroshi Ohtsu, Yasuo Ohashi Kenjiro Kimura, Tatsuo Hosoya, Sadayoshi Ito, Masaaki Inaba, Yasuhiko Tomino, Shunya Uchida, Hirofumi Makino, Seiichi Matsuo, Hisashi Yamanaka, Tetsuya Yamamoto, Iwao Ohno, Yugo Shibagaki, Satoshi Iimuro, Naohiko Imai, Masanari Kuwabara, Hiroshi Hayakawa, Tadao Akizawa, MD, PhD, Tamio Teramoto, MD, PhD, Hiroshi Kasanuki, MD, PhD, Kenichi Yoshimura, PhD, Kenjiro Kimura, MD, PhD, Tatsuo Hosoya, MD, PhD, Yugo Shibagaki, MD, Iwao Ohno, MD, Hiroshi Sato, MD, Shunya Uchida, MD, Satoshi Horikoshi, MD, Syoichi Maruyama, MD, Masahiko Inaba, MD, Yuji Moriwaki, MD, Haruhito Uchida, MD, Nagayuki Kaneshiro, MD, Naohiko Imai, MD, Hidekazu Moriya, MD, Yasuhiro Komatsu, MD, Shinya Kaname, MD, Kazunari Hanaoka, MD, Makoto Ogura, MD, Masato Ikeda, MD, Kenji Kasai, MD, Akira Sugiura, MD, Kazushi Takahashi, MD, Kenichiro Kojima, MD, Kosaku Nitta, MD, Hirofumi Tamai, MD, Hiroshi Nagaya, MD, Senji Okuno, MD, Ryusuke Kakiya, MD, Hiroya Takeoka, MD, Kyouji Hirata, MD, Kenichiro Asano, MD, Yasuo Fukaya, MD, Yasushi Iwaida, MD, Yasuo Tsuneda, MD, Shigeaki Nishimura, MD, Takeyuki Hiramatsu, MD, Yoshitaka Isaka, MD, Takafumi Ito, MD, Yukio Yuzawa, MD, Kunihiro Yamagata, MD, Tadashi Sofue, MD, Yoshimi Jinguji, MD, Keita Hirano, MD, Kazuhiro Matsuyama, MD, Teruhiko Mizumoto, MD, Yuko Shibuya, MD, Masahiro Sugawara, MD, Moritoshi Kadomura, MD, Yasuaki Teshima, MD, Hiroshi Ohtani, MD, Hiroki Kamata, MD, Susumu Okawara, MD, Masaki Fukushima, MD, Katsumi Takemura, MD, Eriko Kinugasa, MD, Masami Kogure, MD, Yoichi Ehara, MD  American Journal of Kidney Diseases  Volume 72, Issue 6, Pages 798-810 (December 2018) DOI: 10.1053/j.ajkd.2018.06.028 Copyright © 2018 The Authors Terms and Conditions

Figure 1 Consolidated Standards of Reporting Trials (CONSORT) diagram. ∗Found after the initiation of administration. Abbreviation: eGFR, estimated glomerular filtration rate. American Journal of Kidney Diseases 2018 72, 798-810DOI: (10.1053/j.ajkd.2018.06.028) Copyright © 2018 The Authors Terms and Conditions

Figure 2 Time-course changes in estimated glomerular filtration rates (eGFRs) from week 0 through week 108 of treatment. (A) Study population; (B) proteinuria, negative/positive; (C) serum creatinine level less than or equal to or greater than the median. eGFRs were determined using generalized estimating equation repeated-measures analysis, with time as a categorical variable. Mean ± 95% confidence interval. American Journal of Kidney Diseases 2018 72, 798-810DOI: (10.1053/j.ajkd.2018.06.028) Copyright © 2018 The Authors Terms and Conditions

Figure 3 Time course changes in serum uric acid concentrations from week 0 through week 108 of treatment. Mean ± 95% confidence interval. American Journal of Kidney Diseases 2018 72, 798-810DOI: (10.1053/j.ajkd.2018.06.028) Copyright © 2018 The Authors Terms and Conditions

Figure 4 Time course changes in blood pressures from week 0 through week 108 of treatment. Mean ± 95% confidence interval. ∗P<0.05, ∗∗P<0.01. Abbreviations: DBP, diastolic blood pressure; SBP, systolic blood pressure. American Journal of Kidney Diseases 2018 72, 798-810DOI: (10.1053/j.ajkd.2018.06.028) Copyright © 2018 The Authors Terms and Conditions