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Recent advances in renal urate transport: characterization of candidate transporters indicated by genome-wide association studies

  • Review article
  • The 36th IUPS Satellite Symposium: The Kidney and Hypertension
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Humans have higher serum uric acid levels than other mammalian species owing to the genetic silencing of the hepatic enzyme uricase that metabolizes uric acid into allantoin. Urate (the ionized form of uric acid) is generated from purine metabolism and it may provide antioxidant defense in the human body. Despite its potential advantage, sustained hyperuricemia has pathogenetic causes in gout and renal diseases, and putative roles in hypertension and cardiovascular diseases. Since the kidney plays a dominant role in maintaining plasma urate levels through the excretion process, it is important to understand the molecular mechanism of renal urate handling. Although the molecular identification of a kidney-specific urate/anion exchanger URAT1 in 2002 paved the way for successive identification of several urate transport-related proteins, the entire picture of effective renal urate handling in humans has not yet been clarified. Recently, several genome-wide association studies identified a substantial association between uric acid concentration and single nucleotide polymorphisms in at least ten genetic loci including eight transporter-coding genes. In 2008, we functionally characterized the facilitatory glucose transporter family member SLC2A9 (GLUT9), one of the candidate genes for urate handling, as a voltage-driven urate transporter URATv1 at the basolateral side of renal proximal tubules that comprises the main route of the urate reabsorption pathway, in tandem with URAT1 at the apical side. In this review, recent findings concerning these candidate molecules are presented.

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Acknowledgments

The authors thank all the members of their laboratories who have contributed to the work discussed in this review. This work was supported in part by grants from JSPS (KAKENHI 21390073, 21659216, 21890245), Takeda Science Foundation, Gout Research Foundation of Japan, The Nakatomi Foundation and Kyorin University School of Medicine (Collaborative Project 2008 and 2009).

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, Japan

    Naohiko Anzai & Promsuk Jutabha

  2. Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan

    Naohiko Anzai, Promsuk Jutabha, Sirirat Amonpatumrat-Takahashi & Hiroyuki Sakurai

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  1. Naohiko Anzai
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  2. Promsuk Jutabha
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  3. Sirirat Amonpatumrat-Takahashi
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  4. Hiroyuki Sakurai
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Correspondence to Naohiko Anzai.

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Anzai, N., Jutabha, P., Amonpatumrat-Takahashi, S. et al. Recent advances in renal urate transport: characterization of candidate transporters indicated by genome-wide association studies. Clin Exp Nephrol 16, 89–95 (2012). https://doi.org/10.1007/s10157-011-0532-z

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