Metabolic Syndrome and Uric Acid Nephrolithiasis

The metabolic syndrome describes a cluster of metabolic features that increases the risk for type 2 diabetes mellitus and cardiovascular disease. The prevalence of uric acid nephrolithiasis is higher among stone-forming patients with features of the metabolic syndrome such as obesity and/or type 2 diabetes mellitus. The major determinant in the development of idiopathic uric acid stones is an abnormally low urinary pH. The unduly urinary acidity in uric acid stone formers increasingly is recognized to be one of the features observed in the metabolic syndrome. Two major abnormalities have been implicated to explain this overly acidic urine: (1) increased net acid excretion, and (2) impaired buffering caused by defective urinary ammonium excretion, with the combination resulting in abnormally acidic urine. New information is emerging linking these defects to changes in insulin signaling in the kidney. This article reviews the epidemiologic and metabolic studies linking uric acid nephrolithiasis with the metabolic syndrome, and examines the potential mechanisms underlying the unduly acidic urine in these conditions.