The physiology of uric acid and the impact of end‐stage kidney disease and dialysis

Uric acid-mediated biological effects are milieu dependent. In a physiological milieu, serum uric acid serves as an antioxidant; when homeostasis is perturbed, divergent effects are observed depending on the clinical context. Several epidemiologic studies indicated the presence of a direct relationship between higher concentrations of serum uric acid and cardiovascular mortality; yet not all studies support this conclusion. Although high serum levels of uric acid are associated with higher mortality in patients with nondialysis-dependent chronic kidney disease and perhaps in those with end-stage kidney disease receiving peritoneal dialysis, the opposite relationship is seen in patients with end-stage kidney disease on hemodialysis. This review discusses the pathologic mechanisms associated with elevated serum uric acid levels by clinical context; examines the interplay between uric acid metabolism and modality of renal replacement therapy; and presents hypotheses to rationalize the disparate associations between incremental levels of serum uric acid and survival across the continuum of kidney disease and by type of renal replacement therapy.