Induction of Acute Cyclosporine Nephrotoxicity in Pig

Kim, Jin Young; Lim, Sun Woo; Ahn, Kyung Ok; Song, Hyun Kuk; Ghee, Jung Yeon; Chung, Byung Ha; Kim, Yong Soo; Bang, Byung Kee; Yang, Chul Woo

Abstract

PURPOSE: Pigs are promising donor species for xenotransplantation. This study was performed to examine acute cyclosporine (CsA) nephrotoxicity in a pig model.
METHODS
Adult pigs were treated daily for 1 week with vehicle (VH), or 7.5 mg/kg (CsA7.5), 15 mg/kg (CsA15), and 30 mg/kg (CsA30) CsA. The renal function, electrolyte levels, whole- blood CsA levels, and histopathological results (vacuolization and tubulointerstitial fibrosis) were compared among the different treatment groups.
RESULTS
After 1 week of treatment, it was found that CsA induced characteristic lesions that were remarkably similar to those of chronic CsA nephropathy in humans. Compared with the results obtained for the VH group, CsA reduced renal function and yielded poor histopathological results. With an increase in the CsA concentration, the renal function and histological parameters worsened in a dose-dependent manner.
CONCLUSION
The study showed that CsA dose-dependently induced renal injury in a pig model. These results provide basic data to estimate or prevent the adverse renal effects of immunosuppressants during porcine xenotransplantation in the future.