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Association of serum uric acid levels with the risk of development or progression of albuminuria among Japanese patients with type 2 diabetes: a prospective cohort study [Diabetes Distress and Care Registry at Tenri (DDCRT 10)]

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Abstract

Aims

To assess the prospective association between baseline serum uric acid level and subsequent risk of development or progression in albuminuria.

Methods

Longitudinal data were obtained from 2518 patients with type 2 diabetes in the development cohort and registered in a Japanese diabetes registry. To assess the independent correlations between baseline serum uric acid quartiles and either the development or progression of diabetic nephropathy for 2 years, the Cox proportional hazards model was used and adjusted for potential confounders.

Results

The mean patient age, body mass index, and glycated hemoglobin (HbA1c) level were 66.1 years, 24.6 kg/m2, and 7.5 % (57.6 mmol/mol), respectively. The baseline serum uric acid levels, with mean values of 3.6, 4.9, 5.8, and 7.3 mg/dL from the first to fourth quartiles, were significantly associated with the urinary albumin/creatinine ratio at baseline (p < 0.001). Baseline uric acid levels were not significantly associated with the development of nephropathy, but they were with the progression of nephropathy. The multivariable-adjusted hazards ratios for the progression from microalbuminuria to macroalbuminuria were 2.17 [95 % confidence interval (CI) 1.15–4.08; p = 0.016], 3.04 (95 % CI 1.67–5.53; p < 0.001), and 3.56 (95 % CI 1.83–6.93; p < 0.0011) for the first, third, and fourth quartiles of serum uric acid levels, respectively, as compared to that for the second quartile. We did not observe significant association between uric acid levels and change in estimated glomerular filtration rate.

Conclusions

Low and high serum uric levels, independent of possible confounders, were associated with a subsequent risk of progression, not development, in albuminuria in type 2 diabetes patients. Therefore, serum uric acid levels may be useful for predicting the future risk of progression of microalbuminuria.

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Acknowledgments

This study was partially supported by the Manpei Suzuki Diabetes Foundation and JSPS KAKENHI (Grant No. 25460641); however, they played no role in the study design or conduct, data collection, analysis, or interpretation, and the preparation, review, or approval of the manuscript. We would like to especially thank Yukari Moritsuji, Yuki Fujita, Noriko Nakamura, and Yoko Sakamoto (Department of Endocrinology, Tenri Hospital) for their clerical support. The authors would like to thank Enago (www.enago.jp) for the English language review.

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Authors and Affiliations

  1. Department of Endocrinology, Tenri Hospital, 200 Mishima-cho, Tenri City, Nara, 632-8552, Japan

    Yasuaki Hayashino, Shintaro Okamura & Satoru Tsujii

  2. Department of Diabetology, Nara Medical University, Kashihara, Nara, 634-8521, Japan

    Hitoshi Ishii

Authors
  1. Yasuaki Hayashino
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Corresponding author

Correspondence to Yasuaki Hayashino.

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Conflict of interest

Dr. Okamura reports personal fees from Takeda Pharmaceutical Company, Ltd., personal fees from Daiichi Sankyo Company, Ltd., personal fees from Ono Pharmaceutical Co., Ltd., personal fees from Kissei Pharmaceutical Co., Ltd., outside the submitted work. Dr. Hayashino reports personal fees from Takeda Pharmaceutical Company, Ltd., personal fees from Eli Lilly Japan K.K., personal fees from Daiichi Sankyo Company, Ltd., personal fees from Pfizer Japan Inc, personal fees from Ono Pharmaceutical Co., Ltd., outside the submitted work. Dr. Tsujii reports personal fees from AstraZeneca K.K., personal fees from Daiichi Sankyo Company, Ltd., personal fees from Eli Lilly Japan K.K., personal fees from Mitsubishi Tanabe Pharma Corporation, personal fees from Novo Nordisk Pharma Ltd., personal fees from Ono Pharmaceutical Co., Ltd., personal fees from Sanofi K.K., outside the submitted work. Dr. Ishii reports personal fees from Takeda Pharmaceutical Company, Ltd., personal fees from Eli Lilly Japan K.K., personal fees from Sanofi KK., personal fees from Merck & Co., Inc., personal fees from Astellas Pharma Inc., personal fees from Astellas Pharma Inc., personal fees from Novartis Pharma K.K., personal fees from Mitsubishi Tanabe Pharma Corporation, personal fees from Daiichi Sankyo Company, Ltd., personal fees from Ono Pharmaceutical Co., Ltd, personal fees from AstraZeneca K.K., personal fees from Taisho Toyama Pharmaceutical Co., Ltd, personal fees from SHIONOGI & CO., LTD., personal fees from Kowa Pharmaceutical Co., Ltd, personal fees from Boehringer Ingelheim, outside the submitted work.

Ethical standard

The study was approved by the Ethical Committee of Tenri Hospital, Japan.

Human and Animal Rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed Consent

Informed consent was obtained from all patients for being included in the study.

Additional information

Managed by Massimo Porta.

For the Diabetes Distress and Care Registry at Tenri Study Group.

Members of the Diabetes Distress and Care Registry at Tenri Study Group are listed in the Appendix.

Appendix: Members of the Diabetes Distress and Care Registry at Tenri Study Group

Appendix: Members of the Diabetes Distress and Care Registry at Tenri Study Group

Shintaro Okamura, Miyuki Furuya, Masako Kitatani, Hirohito Kuwata (Department of Endocrinology, Tenri Hospital); Satoru Tsujii (Diabetes Center, Tenri Hospital); Yasuaki Hayashino (Department of Endocrinology, Tenri Hospital, Department of Epidemiology and Healthcare Research, Kyoto University Graduate School of Medicine); Hitoshi Ishii, Tsuyoshi Mashitani (Nara Medical University); Satoshi Matsunaga (Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine); Yaeko Kondo, Naotaka Fujita (Department of Diabetes and Clinical Nutrition, Kyoto University); Rei Ueda (Second Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus); Rie Kurokawa (Osaka Medical Center and Research Institute for Maternal and Child Health); Masami Tanaka (Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine).

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Hayashino, Y., Okamura, S., Tsujii, S. et al. Association of serum uric acid levels with the risk of development or progression of albuminuria among Japanese patients with type 2 diabetes: a prospective cohort study [Diabetes Distress and Care Registry at Tenri (DDCRT 10)]. Acta Diabetol 53, 599–607 (2016). https://doi.org/10.1007/s00592-015-0825-x

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