Insulin resistance increases the risk of urinary stone formation in a rat model of metabolic syndrome

OBJECTIVE To investigate the association between metabolic syndrome and urinary stone disease, and whether insulin resistance associated with adiposity affects the risk of urinary stone formation, using a rat model of metabolic syndrome. MATERIALS AND METHODS Four-week-old male Otsuka Long-Evans Tokushima 'Fatty' (OLETF, a model of human type 2 diabetes and metabolic syndrome) rats, and Long-Evans Tokushima (LETO, a non-diabetic control) rats (10 each) were given a standardized diet and free access to water. Body weight and serum and urinary biochemistry were determined every 4 weeks. Ten-week-old male OLETF and LETO rats were divided into three groups of nine each and treated with vehicle or oral administration of 3 or 10 mg/kg/day pioglitazone, an agent that improves insulin resistance. After 4 weeks, body weight and serum and urinary biochemistry were determined. RESULTS The OLETF rats had significantly lower urinary pH and citrate excretion, and higher urinary uric acid and calcium excretion, than the LETO rats, with increases in body weight, serum triglyceride, glucose and insulin. The administration of pioglitazone to the OLETF rats for 4 weeks significantly increased urinary pH dose-dependently. There was no change in the urinary excretion of citrate, uric acid, calcium, oxalate or magnesium. CONCLUSION These results indicate that metabolic syndrome causes the changes in urinary constituents, leading to increased risk of both uric acid and calcium stone formation. Improvement in insulin resistance, a central cause of metabolic syndrome, might prevent uric acid stone formation by raising urinary pH.