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Notably, deposition of MSU crystals can even occur during phases of asymptomatic hyperuricemia ( 2 Initiation phase: uric acid supersaturation in body fluids and altered physicochemical conditions 2.1 Causes of hyperuricemia and its effects on the local microenvironment The fundamental pathophysiological basis of tophus formation is the persistent elevation of serum uric acid above its solubility threshold, leading to urate supersaturation