Use of capecitabine to prevent acute renal allograft rejection in dog erythrocyte antigen-mismatched mongrel dogs.
OBJECTIVE
To assess efficacy and toxicity of a capecitabine (CAP)-based regimen for preventing rejection of renal allografts in dog erythrocyte antigen (DEA)-mismatched mongrel dogs.


METHODS
Prospective, pilot study.


METHODS
Eight healthy, unrelated, DEA mismatched, adult mongrel dogs.


METHODS
All dogs received CAP, starting at 50 mg/m2 PO b.i.d. 4 days preoperatively, increasing to 200 mg/m2 PO b.i.d. by the day of surgery. All dogs received cyclosporine-A (CsA) and prednisolone starting 2 days preoperatively. Standard heterotopic renal transplantation with native nephrectomy was performed. After 90 days, surviving dogs were euthanatized and histopathologic examination was performed.


RESULTS
Two of 8 dogs developed acute neurotoxicity leading to death or euthanasia within 5 days of surgery. For the 6 remaining dogs, there were no statistically significant changes in complete blood count or serum biochemical values. No opportunistic infections developed during the study period. Five of 6 dogs had no to minimal evidence of graft rejection. Two of 6 dogs developed superficial and pigmentary keratitis. Significant histopathologic findings in all dogs included mild lymphoplasmacytic gastroenteritis, steroid hepatopathy, and corneal epithelial thinning. One dog had moderate interstitial nephritis and pyelitis.


CONCLUSIONS
In this experimental model, a CAP-CsA-prednisolone immunosuppressive regimen was effective in preventing rejection of allografts in DEA-mismatched dogs. Severe, unpredictable neurotoxicity and variable ocular toxicity significantly limit clinical applications at this time.


CONCLUSIONS
A CAP-CsA-prednisolone protocol is an effective, oral immunosuppressive regimen for prevention of allograft rejection in DEA-mismatched mongrel dogs. For clinical application, identification of patients susceptible to toxic side effects would be necessary.
Milovancev
Milan
M
Department of Surgical and Pathobiological Sciences, College of Veterinary Medicine, and the Research Animal Resource Center, University of Wisconsin, Madison, WI 53706-1102, USA.
Schmiedt
Chad W
CW
Bentley
Ellison
E
Schwab
Michelle
M
Dubielzig
Richard R
RR
Gendron-Fitzpatrick
Annette P
AP
McAnulty
Jonathan F
JF
D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D001772:Blood Cell Count / 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 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control / Q000662:veterinary*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000662:veterinary*; D009392:Nephrectomy / Q000662:veterinary; D010865:Pilot Projects; D011183:Postoperative Complications / Q000453:epidemiology / Q000401:mortality / Q000662:veterinary; D011446:Prospective Studies; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000662:veterinary; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D007166:Immunosuppressive Agents; D003841:Deoxycytidine; D000069287:Capecitabine; D016572:Cyclosporine; D005472:Fluorouracil