Use of capecitabine after renal allograft transplantation in dog erythrocyte antigen-matched dogs.
OBJECTIVE
To investigate the use of a capecitabine (CAP)-based regimen after renal transplantation in dogs.


METHODS
Prospective, pilot study.


METHODS
Healthy, unrelated, dog erythrocyte antigen (DEA)-matched, adult beagles.


METHODS
Standard heterotopic renal transplantation with native nephrectomy was performed in 7 dogs. Dogs received oral, twice daily, CAP (250 mg/m2), cyclosporine-A (CsA) (4 mg/kg), ketoconazole (5 mg/kg), and prednisolone (0.25 mg/kg). After 90 days the surviving dogs were euthanatized and complete necropsy was performed.


RESULTS
Seven transplants were performed. All dogs survived surgery. Six dogs had acute neurotoxicity, which resulted in death or euthanasia of 2 dogs within 2 days of surgery. In the remaining dogs, toxicity resolved rapidly with cessation of drug administration. Thereafter, modification of the regimen minimized toxicity. The 5 remaining dogs survived to study end; 4 dogs had no evidence of graft rejection. Necropsy examination was mostly unremarkable in all dogs. There were no major changes in CBC or biochemical values, except for a significant increase in serum calcium.


CONCLUSIONS
CAP appeared well tolerated in most dogs. Toxicity occurred but abated with modification of the drug regimen. Efficacy for postoperative immunosuppression cannot be determined by this study, although results are promising.


CONCLUSIONS
CAP-CsA-prednisolone is an effective, oral immunosuppressive regimen for prevention of acute allograft rejection in DEA-matched beagles. Further studies on dose, toxicity, and efficacy compared with current immunosuppressive regimens are needed before use in clinical practice.
Schmiedt
Chad
C
Department of Surgical Sciences, College of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706-1102, USA.
Penzo
Chiara
C
Schwab
Michelle
M
Dubielzig
Richard
R
McAnulty
Jonathan
J
D000818:Animals; D001774:Blood Chemical Analysis / Q000662:veterinary; D000069287:Capecitabine; D016572:Cyclosporine / Q000627:therapeutic use; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004285:Dogs / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006084:Graft Rejection / Q000662:veterinary; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007654:Ketoconazole / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000662:veterinary*; D009392:Nephrectomy / Q000662:veterinary; D010865:Pilot Projects; D011239:Prednisolone / Q000627:therapeutic use; D011446:Prospective Studies; D014181:Transplantation Immunology; D014184:Transplantation, Homologous / Q000662:veterinary; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D003841:Deoxycytidine; D000069287:Capecitabine; D016572:Cyclosporine; D011239:Prednisolone; D007654:Ketoconazole; D005472:Fluorouracil