ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2022 and some content may be unavailable. To unlock all content for 2022, please visit the archives.

Abstract: TH-PO352

Caffeine Inhibits Basal and Insulin-Activated Urate Transport

Session Information

Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders

  • 1001 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Basic


  • Mount, David B., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Mandal, Asim, Brigham and Women's Hospital, Boston, Massachusetts, United States

Caffeine inhibits insulin signaling and has beneficial effects in metabolic syndrome/hyperinsulinemia. Coffee drinking also has beneficial effects in gout, via mechanisms unknown. We hypothesized that caffeine would specifically block insulin-activated urate transport, which in turn mediates the association between hyperinsulinemia and hyperuricemia.


We examined the effect of caffeine and adenosine on 14C-urate transport in absence and presence of insulin, on activation of insulin signaling pathways in human renal epithelial cell line (PTC-05), and on individual urate transporters expressed in Xenopus laevis oocytes.


We found that both caffeine and adenosine inhibited both basal and insulin-stimulation of net 14C-urate uptake in PTC-05 proximal tubular cells. In Xenopus laevis oocytes expressing individual urate transporters, caffeine efficiently inhibited the basal urate transport activity of GLUT9 isoforms, OAT4, OAT1, OAT3, NPT1, ABCG2 and ABCC4 at >0.2 mM; adenosine had weaker effects on basal urate transport. The IC-50 of caffeine for basal urate transport was 613 µM for GLUT9a, 1080 µM for GLUT9b, 145 µM for OAT1, 8 µM for murine OAT3, 582 µM for OAT10, and 4860 µM for URAT1. Caffeine at lower concentrations (<0.2 mM) very effectively inhibited insulin-activation of urate transport activity of GLUT9, OAT10, OAT1, OAT3, NPT1, ABCG2 and ABCC4, with concomitant inhibition of insulin-activated Akt and ERK phosphorylation. For example, the IC-50 of caffeine for insulin-activated GLUT9a urate transport was 205 µM. In contrast, adenosine had no effect on insulin-activated AKT and ERK phosphorylation.


Caffeine and adenosine inhibit basal urate transport mediated by multiple urate transporters. Caffeine also potently inhibits insulin-activated urate transport, with a significantly lower IC-50 for GLUT9a insulin-activated transport versus basal transport. To the extent that GLUT9a is postulated to be the major insulin-activated reabsorptive pathway for urate in the proximal tubule (Front Physiol. 2021 Aug 2;12:713710), caffeine potentially provides a unique in vivo probe for insulin-activated renal urate reabsorption. Additionally, these results provide an explanation for the beneficial effects of caffeine in gout, worthy of further exploration.


  • Other NIH Support