Use of urinary metabolomics to evaluate the effect of hyperuricemia on the kidney

Food Chem Toxicol. 2014 Dec:74:35-44. doi: 10.1016/j.fct.2014.08.017. Epub 2014 Sep 6.

Abstract

Clinical studies show that hyperuricemia is a risk factor in the progression and development of cardiovascular and metabolic disease. Elevated serum levels of uric acid induce renal injury via an inflammation response, but the detailed mechanism is still under study. To better understand the effect of hyperuricemia on the kidney, we used gas chromatography-mass spectrometry-based metabolomics to investigate the role of uric acid in the mouse kidney. Partial least-squares discriminant analysis revealed significant differences between control and hyperuricemia groups in urine metabolic profiles. We identified 33 metabolites from 76 highly reproducible peaks and found abnormal uric acid levels related to comprehensive kidney injury, including excretive function and energy metabolism. Additionally, inflammation induced by the interleukin 6/signal transducer and activator of transcription 3 signaling pathway participated in hyperuricemia-induced kidney injury. This study helps understand the relationship between hyperuricemia and kidney injury. Metabolomics may be a useful strategy for early diagnosis of kidney damage.

Keywords: Hyperuricemia; IL-6/STAT3 signaling; Kidney injury; Urinary metabolomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / urine
  • Animals
  • Blood Urea Nitrogen
  • Creatinine / blood
  • Hyperuricemia / complications*
  • Hyperuricemia / metabolism
  • Hyperuricemia / urine
  • Interleukin-6 / physiology
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Metabolomics* / methods
  • Mice, Inbred ICR
  • Nephrons / drug effects
  • Proteinuria / etiology
  • Proteinuria / metabolism
  • STAT3 Transcription Factor / physiology
  • Signal Transduction / physiology
  • Uric Acid / blood

Substances

  • Interleukin-6
  • STAT3 Transcription Factor
  • Uric Acid
  • Creatinine