Time course of organic anion transporter 5 (Oat5) urinary excretion in rats treated with cisplatin: a novel urinary biomarker for early detection of drug-induced nephrotoxicity

Abstract

Cisplatin is a widely used citostatic drug employed in the treatment of many solid tumors. Its principal side-effect is nephrotoxicity. The organic anion transporter 5 (Oat5) is exclusively expressed in the kidneys. The aim of this study was to evaluate the time course of Oat5 urinary excretion and changes in conventional biomarkers, such as creatinine and urea plasma levels (Urp and Crp), and protein and glucose urinary levels (Pu and Gluu), between others, and compared them to the onset and progression of histological changes after cisplatin treatment. Male Wistar rats were treated with cisplatin with 5 mg/kg b.w., i.p., and experiments were carried out after 2, 4, 7 and 14 days of treatment. Two days after cisplatin administration, only Oat5 urinary excretion was found markedly modified. On day 4, Urp, Crp, PU and GluU were increased. By the seventh day, a severe impairment in tubular architecture was observed, and from this point and thereon, Oat5 urinary excretion and PU showed a tendency to return to their basal values. Meanwhile, Urp, Crp and GluU tended to return to their basal values by the day 14 of treatment, when kidney morphology showed an important recovery. So Oat5 urinary abundance was elevated 2 days after cisplatin treatment, when no modifications of traditional markers of renal injury were still observed. Therefore, the results showed in this work, in addition to previous data obtained by our group, propose that Oat5 urinary excretion might potentially serve as a noninvasive early biomarker of cisplatin-induced nephrotoxicity.