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Time to target uric acid to retard CKD progression

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Abstract

Uric acid (UA) remains a possible risk factor of chronic kidney disease (CKD) but its potential role should be elucidated given a fact that multidisciplinary treatments assure a sole strategy to inhibit the progression to end-stage renal disease (ESRD). In clinical setting, most observational studies showed that elevation of serum uric acid (SUA) independently predicts the incidence and the development of CKD. The meta-analysis showed that SUA-lowering therapy with allopurinol may retard the progression of CKD but did not reach conclusive results due to small-sized studies. Larger scale, randomized placebo-controlled trials to assess SUA-lowering therapy are needed. Our recent analysis by propensity score methods has shown that the threshold of SUA should be less than 6.5 mg/dL to abrogate ESRD. In animal models an increase in SUA by the administration of oxonic acid, uricase inhibitor, or nephrectomy can induce glomerular hypertension, arteriolosclerosis including afferent arteriolopathy and tubulointerstitial fibrosis. The ever-growing discoveries of urate transporters prompt us to learn UA metabolism in the kidney and intestine. One example is that the intestinal ABCG2 may play a compensatory role at face of decreased renal clearance of UA in nephrectomized rats, the trigger of which is not a uremic toxin but SUA itself. This review will summarize the recent knowledge on the relationship between SUA and the kidney and try to draw a conclusion when and how to treat asymptomatic hyperuricemia accompanied by CKD. Finally we will address a future perspective on UA study including a Mendelian randomization approach.

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Acknowledgments

We thank all of the doctors at the Division of Nephrology, Teikyo University School of Medicine, Tokyo, Japan, for their cooperation. This work was supported in part by a Grant-in-Aid for Progressive Renal Diseases Research on Rare and Intractable Disease, from the Ministry of Health, Labour and Welfare of Japan (to SU) and Gout Research Foundation (to SU). The funders had no role in decision to publish and preparation of the manuscript.

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    Authors and Affiliations

    1. Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan

      Takanori Kumagai, Tatsuru Ota, Yoshifuru Tamura, Shigeru Shibata & Shunya Uchida

    2. Support for Community Medicine Endowed Chair, Teikyo University School of Medicine, Tokyo, 173-8605, Japan

      Takanori Kumagai

    3. Department of Nephrology, Tianjin First Central Hospital, Tianjin, China

      Wen Xiu Chang

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    1. Takanori Kumagai
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    2. Tatsuru Ota
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    3. Yoshifuru Tamura
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    4. Wen Xiu Chang
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    5. Shigeru Shibata
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    6. Shunya Uchida
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    Correspondence to Shunya Uchida.

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    T. Kumagai and S. Uchida equally contributed to this work.

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    Kumagai, T., Ota, T., Tamura, Y. et al. Time to target uric acid to retard CKD progression. Clin Exp Nephrol 21, 182–192 (2017). https://doi.org/10.1007/s10157-016-1288-2

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    • DOI: https://doi.org/10.1007/s10157-016-1288-2

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