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 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.