The Pathophysiology of Uric Acid on Renal Diseases

Asymptomatic hyperuricemia was regarded as a marker and considered secondary to some pathological conditions such as hypertension. During the last 16 years, a vast amount of experimental work has shown that uric acid can cause intracellular alterations that lead to cardiovascular, renal, and metabolic disease. Epidemiological and clinical studies support this notion in specific populations. However, the clinical studies done so far are of such a small number that it is difficult to reach a consensus in regard to the benefit of treating asymptomatic hyperuricemia.

Mild hyperuricemia in rodents induces hypertension associated to renal microvascular disease, tubulointerstitial inflammation, vasoconstriction, and glomerular hypertension. The cellular mechanisms that lead to those outcomes require an increase in intracellular concentrations of uric acid inducing oxidative stress that then activates the synthesis and secretion of proinflammatory factors and vasoconstrictive substances, and diminishes the bioavailability of nitric oxide produced by eNOS. Uric acid also induces proliferation, senescence, and fat accumulation or inhibits insulin secretion, depending on the cell type. Extracellular uric acid can act as an antioxidant; however, when it crystallizes it also induces the activation of prooxidant and proinflammatory pathways resulting in renal lesion. Key Messages: Experimental evidence shows that uric acid is a true mediator for cardiovascular, renal, and metabolic diseases. However, there is still need for greater and well-controlled intervention studies in humans to define whether treating asymptomatic hyperuricemia is worthwhile or not.