Uric acid: bystander or culprit in hypertension and progressive renal disease?

In humans, uric acid is the main urinary metabolite of purines. Serum levels are higher compared with other mammalians. Uric acid is an antioxidant and perhaps helps to control blood pressure during a low Na+ diet through stimulation of the renin-angiotensin system. Serum uric acid is also considered a marker of tubular reabsorption and 'effective' circulating blood volume. Moreover, hyperuricemia seems to be a cofactor in Na+ -sensitive hypertension, a marker and possibly itself responsible for microvascular damage through stimulation of the renin-angiotensin system, inhibition of endothelial nitric oxide, and proliferative effects on vascular smooth muscle. As fructose-rich diets increase uric acid levels, hyperuricemia may also play a role in the metabolic syndrome, triggering insulin resistance and hypertension.A number of studies on rats rendered hyperuricemic by administration of uricase inhibitors have recently confirmed induction of arterial hypertension and microvascular injury, particularly in the remnant kidney or in cyclosporine-induced renal fibrosis.