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Sex Differences in Urate Handling.

Victoria L Halperin Kuhns1, Owen M Woodward1

  • 1Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

International Journal of Molecular Sciences
|June 21, 2020
PubMed
Summary

Elevated serum urate (hyperuricemia) is linked to gout and kidney stones. Female sex appears protective, offering insights into urate homeostasis and potential new treatments for related diseases.

Keywords:
ABCG2SLC2A9URAT1goutserum uratesex differencesuric acid

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Area of Science:

  • Urology
  • Nephrology
  • Endocrinology
  • Genetics

Background:

  • Hyperuricemia, characterized by elevated serum urate, is a significant risk factor for gout, kidney stones, renal disease, cardiovascular disease, and metabolic syndrome.
  • Emerging evidence highlights a distinct sex difference in the physiological regulation of urate homeostasis, with females exhibiting a protective effect.

Purpose of the Study:

  • To review the current understanding of urate's role in disease pathogenesis.
  • To explore the mechanisms underlying sex differences in urate homeostasis and renal handling.
  • To discuss the implications of these findings for therapeutic strategies.

Main Methods:

  • Comprehensive literature review of studies on hyperuricemia, urate homeostasis, and sex differences.
  • Analysis of findings from genome-wide association studies (GWAS) related to serum urate levels.
  • Examination of data from novel animal models of hyperuricemia.

Main Results:

  • The female sex demonstrates a protective role in the context of hyperuricemia-related pathologies.
  • Significant genetic factors influencing serum urate levels have been identified through GWAS.
  • Specific renal urate transporters are differentially regulated by sex, impacting urate excretion.

Conclusions:

  • Sex differences in urate handling are crucial for understanding physiological regulation and disease development.
  • Leveraging these sex-based distinctions can pave the way for novel therapeutic approaches to hyperuricemia and associated conditions.
  • Further research into sex-specific mechanisms is warranted to optimize treatment strategies.