The role of uric acid in renal damage - a history of inflammatory pathways and vascular remodeling

Abstract

The association of hyperuricemia with cardiovascular risk, hypertension, atherosclerosis, metabolic syndrome, mortality, and chronic kidney disease has been largely described in clinical studies. Several pathogenetic mechanisms explaining uric acid mediated renal damage have been hypothesized, including crystal deposition, oxidative stress, arteriolosclerosis, and glomerular hypertension. Currently, two explanations for hyperuricemia-induced renal injury are the most widely accepted. Firstly, the fact that uric acid is recognized by receptors involved in the innate immune response as a dangerous molecule appears to be a powerful trigger for the inflammatory cascade, which ultimately lead to renal fibrosis. Secondly, serum uric acid has been demonstrated to be implicated in the renin-angiotensin system activation and nitric oxide synthesis inhibition, which promote endothelial dysfunction and proliferation of vascular smooth muscle cells, resulting in glomerulosclerosis and interstitial fibrosis. In this review, we focus on experimental data demonstrating pathophysiological mechanisms linking uric acid to inflammation and oxidative stress, which contribute to the development and progression of renal injury. In addition, we describe endothelial and vascular dysfunction crucial playmakers in kidney impairment induced by uric acid.

Keywords

Uric acid / inflammation / atherosclerosis / kidney disease

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