Improving cardiovascular and renal outcomes in gout: what should we target?

Nat Rev Rheumatol. 2014 Nov;10(11):654-61. doi: 10.1038/nrrheum.2014.124. Epub 2014 Aug 19.


Epidemiological and experimental studies have shown that hyperuricaemia and gout are intricately linked with hypertension, metabolic syndrome, chronic kidney disease and cardiovascular disease. A number of studies suggest that hyperuricaemia and gout are independent risk factors for the development of these conditions and that these conditions account, in part, for the increased mortality rate of patients with gout. In this Review, we first discuss the links between hyperuricaemia, gout and these comorbidities, and present the mechanisms by which uric acid production and gout might favour the development of cardiovascular and renal diseases. We then emphasize the potential benefit of urate-lowering therapies on cardiovascular and renal outcomes in patients with hyperuricaemia. The mechanisms that link elevated serum uric acid levels and gout with these comorbidities seem to be multifactorial, implicating low-grade systemic inflammation and xanthine oxidase (XO) activity, as well as the deleterious effects of hyperuricaemia itself. Patients with asymptomatic hyperuricaemia should be treated by nonpharmacological means to lower their SUA levels. In patients with gout, long-term pharmacological inhibition of XO is a treatment strategy that might also reduce cardiovascular and renal comorbidities, because of its dual effect of lowering SUA levels as well as reducing free-radical production during uric acid formation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allopurinol / therapeutic use
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / prevention & control*
  • Colchicine / therapeutic use
  • Diabetes Mellitus, Type 2 / complications
  • Disease Management
  • Gout / complications
  • Gout / drug therapy*
  • Gout Suppressants / therapeutic use*
  • Humans
  • Hyperuricemia / complications
  • Hyperuricemia / drug therapy*
  • Inflammation
  • Metabolic Syndrome / complications
  • Probenecid / therapeutic use
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / prevention & control*
  • Treatment Outcome
  • Uricosuric Agents / therapeutic use*
  • Xanthine Oxidase / antagonists & inhibitors*


  • Gout Suppressants
  • Uricosuric Agents
  • Allopurinol
  • Xanthine Oxidase
  • Probenecid
  • Colchicine