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Intensive uric acid-lowering therapy in CKD patients: the protocol for a randomized controlled trial

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Abstract

Background

Hyperuricemia would be a risk factor for the development/progression of CKD. However, several studies showed U-shape association between serum uric acid level and renal impairment, suggesting that hypouricemia was rather associated with renal dysfunction. Perhaps, there is the optimal target level of serum UA for renal function.

Methods

The Target-UA study is a multicenter randomized controlled trial. Eligible CKD patients (eGFR ≥ 30, < 60 mL/min/1.73 m2 and urine protein < 0.5 g/gCr or urine albumin to creatinine ratio (ACR) < 300 mg/gCr) with serum UA ≥ 8.0 mg/dL (≥ 7.0 mg/dl: under the treatment) will be enrolled and be randomly assigned to the intensive therapy group (target serum UA level ≥ 4.0 mg/dL, < 5.0 mg/dL) or the standard therapy group (serum UA level ≥ 6.0 mg/dL, < 7.0 mg/dL). Topiroxostat, a new xanthine oxidase inhibitor, will be administered to treat hyperuricemia. The primary endpoint is a change in logarithmic value of urine ACR between baseline and week 52 of treatment. The secondary endpoints include changes in serum UA, eGFR, urine protein, lipid profile, and onset of composite cardiovascular events, renal events, gouty arthritis, and attack of urolithiasis. The number of subjects has been set to be 185 in each group for a total of 370.

Discussion

This is the first study, to the best of our knowledge, to determine the optimal target level of serum UA for renal protection and is expected to lead to progress in CKD treatment.

Trial registration

(UMIN000026741 and jRCTs051180146).

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Personal data protection and confidentiality

Personal information and data will be converted to an anonymous, unique identification code unrelated to any personal information. The data center and person(s) in charge of statistical analysis will handle patient data using the identification code numbers.

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Funding

This study is funded by Fuji Yakuhin Co., Ltd.

Author information

Authors and Affiliations

  1. Nara Medical University Hospital, Kashihara, Japan

    Masato Kasahara

  2. Kyoto University Hospital, Kyoto, Japan

    Yoshihiro Kuwabara

  3. Osaka University, Suita, Japan

    Toshiki Moriyama

  4. Shimane University, Matsue, Japan

    Kazuaki Tanabe

  5. Kyoto Medical Center, Kyoto, Japan

    Noriko Satoh-Asahara

  6. Katsuya Clinic, Amagasaki, Japan

    Tomohiro Katsuya

  7. Hiramitsu Heart Clinic, Nagoya, Japan

    Shinya Hiramitsu

  8. Shimada Hospital, Kumamoto, Japan

    Hidetaka Shimada

  9. Kyoto University, Kyoto, Japan

    Tosiya Sato

  10. Nara Medical University, Kashihara, Japan

    Yoshihiko Saito

  11. Rakuwakai Otowa Hospital, 2 Otowachinjichō, Yamashina-ku, Kyoto, 607-8062, Japan

    Takahiko Nakagawa

Authors
  1. Masato Kasahara
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  2. Yoshihiro Kuwabara
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  3. Toshiki Moriyama
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  4. Kazuaki Tanabe
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  5. Noriko Satoh-Asahara
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  6. Tomohiro Katsuya
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  7. Shinya Hiramitsu
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  8. Hidetaka Shimada
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  11. Takahiko Nakagawa
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Corresponding author

Correspondence to Takahiko Nakagawa.

Ethics declarations

Conflict of interest

MK is a consultant for Reason Why Inc. and has received honoraria from KYORIN Pharmaceutical Co.,Ltd., and has received grants from DAIICHI SANKYO COMPANY, LIMITED, Mitsubishi Tanabe Pharma Corporation, and FUJI YAKUHIN CO., LTD. SH has received honoraria from Mitsubishi Tanabe Pharma Corporation, Bayer Holding Ltd., MSD K.K., and Takeda Pharmaceutical Company Limited. YS is a consultant for Novartis Pharma K.K., ONO PHARMACEUTICAL CO., LTD., and Mitsubishi Tanabe Pharma Corporation, and has received honoraria from Otsuka Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, DAIICHI SANKYO COMPANY, LIMITED, Siemens Healthcare Diagnostics K.K., MSD K.K., Amgen Astellas BioPharma K.K., AstraZeneca K.K., Kowa Pharmaceutical Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, TEIJIN PHARMA LIMITED, Nippon Shinyaku Co., Ltd., Novartis Pharma K.K., Bayer Holding Ltd., Medtronic, Inc., MOCHIDA PHARMACEUTICAL CO., LTD., Novo Nordisk Pharma Ltd., and has received grants from Japan Society for the Promotion of Science, The Ministry of Health, Labour and Welfare Scientific Research, Japan Agency for Medical Research and Development Astellas Pharma Inc., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, TEIJIN PHARMA LIMITED, Bayer Holding Ltd., DAIICHI SANKYO COMPANY, LIMITED, Ltd., Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., Sanofi K.K., Novartis Pharma K.K., MSD K.K., CHUGAI PHARMACEUTICAL CO., LTD., Kyowa Hakko Kirin Co., Ltd., Nihon Medi-Physics Co.,Ltd., ONO PHARMACEUTICAL CO., LTD., Eli Lilly Japan K.K., FUJI YAKUHIN CO., LTD., Sumitomo Dainippon Pharma Co., Ltd. HS has received consulting fee from Pfizer Japan Inc., and has received honoraria from FUJI YAKUHIN CO., LTD. TN lectured a graduate student who was an employee in FUJI YAKUHIN CO., LTD. for 2 years at Nara medical university, and has two patents regarding to hyperuricemia, and has stock for XORT Therapeutics, and has received grant from FUJI YAKUHIN CO., LTD. Remaining authors have declared that no conflict of interest exists.

Ethical approval

The study was conducted in compliance with the Declaration of Helsinki and according to the Clinical Trials Act (Act No. 16 of April 14, 2017) in Japan. The study protocol was approved by the Nara Medical University Certified Review Board on February 22, 2019 (No. nara0008: CRB5180011). The study shall be started at each site after approval of the protocol by the Ethics Review Committee.

Informed consent

The investigators will give a sufficient explanation of the study using explanatory documents to each patient and written informed consent will be obtained from all individual participants included in the study before primary enrollment.

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Kasahara, M., Kuwabara, Y., Moriyama, T. et al. Intensive uric acid-lowering therapy in CKD patients: the protocol for a randomized controlled trial. Clin Exp Nephrol 24, 235–241 (2020). https://doi.org/10.1007/s10157-019-01815-5

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  • DOI: https://doi.org/10.1007/s10157-019-01815-5

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