Abstract
Idiopathic renal hypouricemia, mainly caused by a defect in a gene (SLC22A12) encoding the urate transporter (URAT1), is a disorder with an incidence of 0.15% in Japan. Patients exhibit an increase in uric acid excretion due to an isolated defect in renal tubular transport of uric acid and are known to be frequently complicated by an exercise-induced acute renal failure (ARF).
The mechanisms for development in exercise-induced ARF in patients with idiopathic renal hypouricemia remain unclear while two possible explanations have been proposed: either urate nephropathy results from an increase in urate production during exercise, or renal reperfusion injury due to vasoconstriction results from an exercise- induced increase in oxygen free radicals and a lack of urate, one of the free radical scavengers.
In this review, we summarized the putative mechanisms regarding the development for exercise-induced ARF in patients with idiopathic renal hypouricemia based on the previous reports. Furthermore, we found the oxidative imbalance after exercise in a patient with idiopathic renal hypouricemia and postulate as a cause for exercise-induced ARF in this condition.
A 15 year-old-girl with idiopathic renal hypouricemia caused by a mutation in the URAT1 gene (compound heterozygous mutation for R90H/W258X) was referred us for further evaluation of exercise-induced ARF. We therefore studied the oxidative balance during and soon after exercise in this girl to investigate causal relationship between idiopathic renal hypouricemia and exercise-induced ARF, after written informed consent was obtained. As a result, her serum level of reactive oxygen species (ROS) increased with decreasing antioxidant potential capacity soon after the initiation of anaerobic stress due to treadmill exercise. Thereafter, serum levels of ROS and antioxidant potential showed a parallel course, returning to the baseline values at 240 min after exercise.
Thus, some patients with idiopathic renal hypouricemia demonstrate oxidative imbalance soon after exercise with a predisposition to exercise-induced ARF and we therefore postulate that oxidative imbalance after exercise in a patient with idiopathic renal hypouricemia plays an important role. Antioxidant properties may alter this imbalance by augmenting the antioxidant activity.
