Elevated serum
uric acid levels are a frequent finding in persons with
obesity,
hypertension, cardiovascular and
kidney disease as well as in those with the cardiorenal
metabolic syndrome (CRS). The increased consumption of a
fructose-rich Western diet has contributed to the increasing incidence of the CRS,
obesity and diabetes especially in industrialized populations. There is also increasing evidence that supports a causal role of high dietary
fructose driving elevations in
uric acid in association with the CRS. Animal and epidemiological studies support the notion that elevated serum
uric acid levels play an important role in promoting
insulin resistance and
hypertension and suggest potential pathophysiological mechanisms that contribute to the development of the CRS and associated
cardiovascular disease and
chronic kidney disease. To this point, elevated serum levels of
uric acid appear to contribute to impaired
nitric oxide production/endothelial dysfunction, increased vascular stiffness, inappropriate activation of the renin-angiotensin-aldosterone system, enhanced oxidative stress, and maladaptive immune and inflammatory responses. These abnormalities, in turn, promote vascular, cardiac and renal
fibrosis as well as associated functional abnormalities. Small clinical trials have suggested that
uric acid-lowering
therapies may be beneficial in such patients; however, a consensus on the treatment of asymptomatic
hyperuricemia is lacking. Larger randomized controlled trials need to be performed in order to critically evaluate the beneficial effect of lowering serum
uric acid in patients with the CRS and those with diabetes and/or
hypertension.