Pathogenesis of and risk factors for gout

Rothenbacher, 2011Roughley, 2015Singh, 2011

Serum uric acid concentration is the most important determinant of developing gout; the incidence of gout increases exponentially in relation to serum uric acid concentration, particularly with concentrations greater than 0.54 mmol/L (9 mg/dL).

Uric acid is formed in the liver from dietary and endogenous purines. Consumption of purine-rich foods (particularly meat and seafood), alcohol (particularly beer and spirits) and fructose-sweetened drinks can increase serum uric acid concentration and the risk of gout in susceptible individuals. Disorders involving a high cell turnover (eg haematological malignancies, severe psoriasis) can also increase serum uric acid concentration and the risk of gout in susceptible individuals.

Uric acid is eliminated by the kidneys (two-thirds) and the gut (one-third). Drugs that inhibit the renal excretion of uric acid can increase serum uric acid concentration and the risk of gout in susceptible individuals. These drugs include thiazide diuretics (often taken as a combination product with an angiotensin converting enzyme inhibitor or angiotensin II receptor blocker), loop diuretics and ciclosporin. Diuretics are the most important cause of secondary gout in middle-aged and older people.

People with gout have a higher prevalence of comorbidities including hypertension, chronic kidney disease, dyslipidaemia, type 2 diabetes and obesity, each of which can increase cardiovascular risk. A high concentration of endogenous insulin, as seen in patients with obesity, also inhibits the renal excretion of uric acid.

Patients who are in a catabolic state (eg in sepsis) or are dehydrated are at an increased risk of developing an acute attack of gout. This often occurs during or immediately following a period of hospitalisation.

Any drug, condition or dietary change that causes a rapid rise or decrease in serum uric acid concentration can precipitate or prolong an acute attack of gout. This includes starting or increasing urate-lowering therapy (without flare prophylaxis) for the management of chronic gout, or implementing other dietary changes for the management of gout (eg stopping excessive alcohol consumption).

Risk factors for developing gout contains a summary of the risk factors for developing gout.