Hyperuricemia and the progression of chronic kidney disease: is uric acid a marker or an independent risk factor?

Hyperuricemia is seen when kidney function declines. Whether elevated uric acid (UA) levels play a role in the initiation and progression of kidney disease is a subject of a great debate. Animal studies demonstrate that elevated UA level is a risk factor for kidney disease. In humans, the relationship between UA and kidney disease is more complicated. Cross-sectional studies show an association of hyperuricemia with the presence of CKD; however, from cross-sectional studies, one cannot determine which came first-the elevated UA level or the kidney disease. UA levels are also associated with other risk factors for kidney disease, including hypertension, metabolic syndrome, and microalbuminuria, but it is not clear whether these are mediators or confounders of a relationship. Observational studies suggest a relationship of UA level with incident CKD, but studies evaluating the relationship with decline in kidney function in established CKD are conflicting. Finally, small clinical trials using allopurinol to lower UA levels provide weak, but potentially promising, evidence that lowering UA levels may retard the progression of CKD. In this article, we will review the evidence of the association of hyperuricemia and CKD.