Uric Acid and Hypertension: An Update With Recommendations

Am J Hypertens. 2020 Jul 18;33(7):583-594. doi: 10.1093/ajh/hpaa044.


The association between increased serum urate and hypertension has been a subject of intense controversy. Extracellular uric acid drives uric acid deposition in gout, kidney stones, and possibly vascular calcification. Mendelian randomization studies, however, indicate that serum urate is likely not the causal factor in hypertension although it does increase the risk for sudden cardiac death and diabetic vascular disease. Nevertheless, experimental evidence strongly suggests that an increase in intracellular urate is a key factor in the pathogenesis of primary hypertension. Pilot clinical trials show beneficial effect of lowering serum urate in hyperuricemic individuals who are young, hypertensive, and have preserved kidney function. Some evidence suggest that activation of the renin-angiotensin system (RAS) occurs in hyperuricemia and blocking the RAS may mimic the effects of xanthine oxidase inhibitors. A reduction in intracellular urate may be achieved by lowering serum urate concentration or by suppressing intracellular urate production with dietary measures that include reducing sugar, fructose, and salt intake. We suggest that these elements in the western diet may play a major role in the pathogenesis of primary hypertension. Studies are necessary to better define the interrelation between uric acid concentrations inside and outside the cell. In addition, large-scale clinical trials are needed to determine if extracellular and intracellular urate reduction can provide benefit hypertension and cardiometabolic disease.

Keywords: blood pressure; fructose; hypertension; renin–angiotensin system; uric acid; xanthine oxidase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Humans
  • Hypertension / blood*
  • Hypertension / drug therapy
  • Hypertension / epidemiology
  • Hypertension / etiology
  • Mendelian Randomization Analysis
  • Uric Acid / blood*
  • Uricosuric Agents / therapeutic use


  • Uricosuric Agents
  • Uric Acid