An Evaluation of Combined Immunosuppression with MNA 715 and Microemulsified Cyclosporine on Renal Allograft Rejection in Mismatched Mongrel Dogs

• Published in: Veterinary surgery 2002-07, Vol.31 (4), p.358-366
• Main Authors: Kyles, Andrew E., Gregory, Clare R., Griffey, Stephen M., Jackson, Joshua, Bernsteen, Lynda, Morris, Randall E.
• Format: Article
• Language: English
• Subjects: Alkynes; Animals; Creatinine - blood; Cyclosporine - therapeutic use; Dog Diseases - drug therapy; Dog Diseases - prevention & control; Dogs; Drug Therapy, Combination; Emulsions; Female; Graft Rejection - drug therapy; Graft Rejection - prevention & control; Graft Rejection - veterinary; Immunosuppressive Agents - therapeutic use; Isoxazoles; Kidney Transplantation - immunology; Kidney Transplantation - veterinary; Nephrectomy - veterinary; Nitriles - therapeutic use; Random Allocation; Survival Analysis; Transplantation, Heterologous - veterinary; Treatment Outcome
• ISSN: 0161-3499; 1532-950X
• DOI: 10.1053/jvet.2002.33615

Objective— To evaluate a combination of MNA 715 and microemulsifed cyclosporine for the prevention of renal allograft rejection in mismatched mongrel dogs. Study design— Randomized, experimental study. Animals— Fourteen female mismatched mongrel dogs. Methods— Heterotopic renal transplantation and bilateral nephrectomy were performed in each dog. Dogs were randomly assigned to receive either MNA 715 and cyclosporine (n = 8) or cyclosporine alone (n = 6). Dogs were killed at 100 days after transplantation or when plasma creatinine exceeded 7 mg/dL. Results— In the cyclosporine and MNA 715 group: 4 dogs survived to 100 days with normal plasma creatinine concentrations; 2 dogs with intestinal intussusceptions were killed at 5 and 8 days, 1 dog with a wound infection and sepsis was killed at 14 days, and 1 dog with a serum creatinine concentration >7 mg/dL was killed at 51 days postoperatively. In the cyclosporine‐alone group: 3 dogs with acute rejection were killed at 6 to 9 days and 3 dogs survived to 100 days. In dogs treated with cyclosporine and MNA 715, survival to histologically confirmed acute rejection was significantly longer (P= .044) and the degree of mononuclear cell infiltration was significantly reduced (P= .040), compared with dogs treated with cyclosporine alone. Conclusions— MNA 715 combined with cyclosporine prolonged allograft survival and reduced the severity of histologic rejection in a clinically relevant renal transplant model. Clinical relevance— An immunosuppressive regimen consisting of MNA715 and microemulsified cyclosporine may be effective in preventing allograft rejection in canine renal transplant patients.