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

Vet Surg. 2002 Jul-Aug;31(4):358-66. doi: 10.1053/jvet.2002.33615.

Abstract

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Alkynes
  • Emulsions
  • Immunosuppressive Agents
  • Isoxazoles
  • Nitriles
  • 2-cyano-3-hydroxy-N-(4-(trifluoromethyl)phenyl)-2-hepten-6-ynamide
  • Cyclosporine
  • Creatinine