An evaluation of combined immunosuppression with MNA 715 and microemulsified cyclosporine on renal allograft rejection in mismatched mongrel dogs

Objective-To evaluate a combination of MNA 715 and microemulsified 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 MNA715 group: 4 dogs survived to 100 clays with normal plasma creatinine concentrations 2 clogs with intestinal intussusceptions were killed at 5 and 8 days. 1 dog with a wound infection and sepsis was killed at 14 clays, 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 clogs 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. (C) Copyright 2002 by The American College of Veterinary Surgeons.