The role of renal urate transporters in exercise induced urate excretion

Urate as an antioxidant molecule, scavenges both reactive oxygene and nitrogen species in the plasma. Because of its association with gout, nephrolitiasis and hypertension, the blood urate levels are tightly regulated by the renal proximal tubules. Several transporters such as URAT1, OAT1, OAT3, UAT and MRP4 localized proximal tubules are involved in the renal handling of urate. Among the several hyperuricemia inducers, exercise by increasing purine catabolism leads to exess uricosuria. However, it is not known whether any adaptive change is developed in the urate handling of the kidneys of exercisers or not. So in this study, we aimed to evaluate the characteristics of URAT1, OAT1 and OAT3 in exercising rats.2,5-3 month old rats divided into 3 groups as control, exercise, hyperuricemia. Animals in exercise group were exhausted on a motor-driven treadmill once a day for 5 days. Hyperuricemia was induced by intraperitoneal administration of uricase inhibitor (oxonic acide, 250 mg.kg-1.day-1). Isolated proximal tubule segments were used to evaluate in vitro OAT1, OAT3 and URAT1 activity. mRNA and protein levels of this transporters were determined by RT-PCR, and western blot analysis respectively.Exercise led to a marked increase in citrate synthase activity and caused proteinuria, glucosuria and hypoglicemia as distinct from the other groups. Plasma and urinary urate increased in the exercise and hyperuricemia groups, however, the excreted and reabsorbed persentage of ultrafiltrated urate did not alter. The data from isolated proximal tubule experiments showed similar basal tubular urate content but total urate transport through URAT1, OAT1 and OAT3 significantly increased in the hyperuricemia group. Both exercise and hyperuricemia caused an increase in the contribution of URAT1 mediated urate transport. Basolateral urate uptake via OAT1 was similar in control and exercise groups but increased in the hyperuricemia. OAT3 mediated urate influx turned to efflux in exercised and hyperuricemic animals. mRNA levels of studied urate transporters in the kidney cortex were found to be depressed both in exercise and hyperuricemia groups, however, this depression reflected to only URAT1 protein levels in both group. Protein levels of other two transporters, OAT1 and OAT3 did not change significantly both in exercising and hyperuricemia group.These alterations observed both in exercise and hyperuricemia groups seem to be atributed to hyperuricemia induced adaptive changes in proximal tubule segments.