Seminars in arthritis and rheumatism
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Urate is the end-product of the purine metabolism in humans. The dominant source of urate is endogenous purines and the remainder comes through diet. Approximately two thirds of urate is eliminated via the kidney with the rest excreted in the feces. ⋯ Hyperuricemia can result in the formation of monosodium urate (MSU) crystals that may be recognized as danger signals by the immune system. This immune response results in the activation of the NLRP3 inflammasome and ultimately in the production and release of interleukin-1β, and IL-18, that mediate both inflammation, pyroptotic cell death, and necroinflammation. It has also been demonstrated that soluble urate mediates effects on the kidney to induce hypertension and can induce long term epigenetic reprogramming in myeloid cells to induce "trained immunity." Together, these sequelae of urate are thought to mediate most of the physiological effects of hyperuricemia and gout, illustrating this biologically active molecule is more than just an "end-product" of purine metabolism.