Analysis of Purine Metabolism to Elucidate the Pathogenesis of Acute Kidney Injury in Renal Hypouricemia
Daisuke Miyamoto,
Nana Sato,
Koji Nagata,
Yukinao Sakai,
Hitoshi Sugihara,
Yuki Ohashi,
Blanka Stiburkova,
Ivan Sebesta,
Kimiyoshi Ichida,
Ken Okamoto
Affiliations
Daisuke Miyamoto
Department of Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan
Nana Sato
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
Koji Nagata
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
Yukinao Sakai
Department of Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan
Hitoshi Sugihara
Department of Endocrinology, Diabetes, and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan
Yuki Ohashi
Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan
Blanka Stiburkova
Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, 11000 Prague, Czech Republic
Ivan Sebesta
Institute of Rheumatology, Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital, 11000 Prague, Czech Republic
Kimiyoshi Ichida
Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan
Ken Okamoto
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
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.
