The biology of urate.
Level 5 - mechanism / opinion, no new human data
Narrative review of mechanistic and biological pathways without new empirical data or systematic review methodology
PubMed 32620198 · doi:10.1016/j.semarthrit.2020.04.007
What was done
The authors synthesized biological, transporter, and pathophysiological literature regarding urate production, elimination, and immunological activity in humans.
What was found
Approximately two-thirds of urate is eliminated through the kidney and the remainder through feces. Only 8% to 12% of filtered urate is ultimately excreted by the kidney, with transport regulated predominantly by URAT1 (encoded by SLC22A12), GLUT9 (SLC2A9), and BCRP (ABCG2). While urate has suggested antioxidant capacity under specific circumstances, the majority of evidence indicates it is pro-inflammatory. Monosodium urate crystals activate the NLRP3 inflammasome, releasing interleukin-1β and IL-18 to mediate inflammation, pyroptotic cell death, and necroinflammation. Soluble urate induces kidney-mediated hypertension and long-term epigenetic reprogramming in myeloid cells ("trained immunity").
Why it matters
This synthesis characterizes urate as a biologically active signaling molecule rather than an inert metabolic byproduct, explaining its role in gout, hypertension, and broader inflammatory diseases.
Limits
The abstract describes a narrative overview and does not provide a systematic search strategy, meta-analytic data, sample sizes, or original empirical measurements.
Cited by
- supports Approximately two-thirds of the purines that produce uric acid in the human body are derived endogenously from tissue recycling rather than from dietary sources.