The most important known cause of gout is elevated levels of uric acid in the blood, as the propensity of MSU crystals to develop in joints increases as uric acid levels rise.[1] Although there is no precise level at which uric acid crystals form, a blood uric acid level above 6.8 mg/dL, clinically referred to as hyperuricemia, is often cited as the level at which gout risk rises dramatically. This is approximately the solubility of MSU in normal saline at 37℃.
In the Framingham Heart Study,[2] the annual occurrence of gout was linearly associated with uric acid levels. In the study, after adjusting for potential confounders, high uric acid (7 to 7.9 mg/dL) was associated with 12 times the risk of gout in women and a 22 times the risk of gout among men compared to having low uric acid (<5 mg/dL), with risks continuing to rise as uric acid levels increased.
Figure 2: The association between uric acid levels and gout incidence
Uric acid levels and gout risk
The primary route of uric acid removal from the body is via urinary excretion. Uric acid in the blood is filtered into the kidneys, where most is reabsorbed back into the blood, with a smaller amount passed into urine. Reductions in uric acid excretion by the kidneys appears to be most responsible for hyperuricemia.[3][4] A lesser pathway of uric acid removal (roughly 1/3 of uric acid excretion) is via the intestinal system.
Uric acid production, meanwhile, is the result of the metabolism of compounds called purines. These purines are derived both endogenously (in the body) from the breakdown of tissues and energy substrates as well as exogenously (outside the body) from eating foods containing purines and purine precursors.
While elevated uric acid is the primary cause of gout, many people with hyperuricemia do not develop gout, suggesting other factors play a role in the development of gout.[5] In particular, the development of MSU crystals likely varies depending on a number of factors, including the temperature and pH of the gout-affected tissues.[6] The body's inflammatory reaction to uric acid crystals is also an important determinant of the occurrence and severity of gout.