Renal hypouricemia is a disease caused by the dysfunction of renal urate transporters. This disease is known to cause exercise-induced acute kidney injury, but its mechanism has not yet been established. To analyze the mechanism by which hypouricemia causes renal failure, we conducted a semi-ischemic forearm exercise stress test to mimic exercise conditions in five healthy subjects, six patients with renal hypouricemia, and one patient with xanthinuria and analyzed the changes in purine metabolites. The results showed that the subjects with renal hypouricemia had significantly lower blood hypoxanthine levels and increased urinary hypoxanthine excretion after exercise than healthy subjects. Oxidative stress markers did not differ between healthy subjects and hypouricemic subjects before and after exercise, and no effect of uric acid as a radical scavenger was observed. As hypoxanthine is a precursor for adenosine triphosphate (ATP) production via the salvage pathway, loss of hypoxanthine after exercise in patients with renal hypouricemia may cause ATP loss in the renal tubules and consequent tissue damage.

Department of Applied Biological Chemistry Graduate School of Agricultural and Life Sciences The University of Tokyo Tokyo 113 8657 Japan

Department of Endocrinology Diabetes and Metabolism Graduate School of Medicine Nippon Medical School Tokyo 113 8603 Japan

Department of Nephrology Graduate School of Medicine Nippon Medical School Tokyo 113 8603 Japan

Department of Pathophysiology Tokyo University of Pharmacy and Life Sciences Tokyo 192 0392 Japan

Department of Pediatrics and Adolescent Medicine 1st Faculty of Medicine Charles University and General University Hospital 11000 Prague Czech Republic

Division of Kidney and Hypertension Jikei University School of Medicine Tokyo 105 8461 Japan

Institute of Rheumatology Institute of Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine Charles University and General University Hospital 11000 Prague Czech Republic

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