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Altered clinicopathology and renal pathology in dogs treated with a clinical dose of cisplatin

Okamoto, Mari Ichii, Osamu Mie, Keiichiro Nishida, Hidetaka Akiyoshi, Hideo 北海道大学

2021.05

概要

Cisplatin (cis-diamminedichloroplatinum, CDDP), an anti-cancer drug, might cause acute kidney injury (AKI). This study investigated clinicopathological changes in dogs treated with a clinical dose of CDDP at 0, 6, 12, 24, 72, and 168 hours. Blood testing revealed an increase of plasma IP at 6, 24, and 72 hours. Plasma Mg increased at 24 hours and decreased at 6 and 72 hours, but other parameters including Na, K, Cl, and Ca as well as blood urea nitrogen did not vary. Only plasma creatine (CRE) was elevated at 168 hours (0.68 ± 0.16 mg/dL), indicating that CDDP did not cause obvious AKI. Increases were observed, however, in urinary protein or albumin/CRE at 6 and 12 hours, urinary N-acetyl-β-D-glucosaminidase (NAG)/CRE at 24 and 72 hours, and in liver-type fatty acid binding protein/CRE at 72 hours, indicating proximal tubule (PT) injuries. Of biomarker candidates, serum and urinary miR-21, serum miR-26a and miR-10a increased. Serum miR-21 was correlated with plasma Ca, IP and Mg levels, and its urinary level correlated positively with plasma CRE and urinary NAG/CRE. Pathologically, distal tubule (DT) dilation, apoptosis in DT and PT, or IL6, IL1B, and TNFA renal expression tended to be elevated at 72 hours. DT dilation, TNFA renal expression, and macrophage infiltrations were prominent at 168 hours. Characteristically, apoptosis in the outer medulla was much greater at 72 hours than at 168 hours. We emphasize the presence of mild renal changes not clearly indicated by routine clinical examinations in CDDP-treated dogs.

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