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

Authors

  • Andrew E. Kyles BVMS, PhD, Diplomate ACVS, Diplomate ECVS,

    1. From the Comparative Transplantation Laboratory, Department of Surgical and Radiological Sciences, and Comparative Pathology Laboratory, School of Veterinary Medicine, University of California, Davis, CA; and Transplantation Immunology, Department of Cardiovascular Surgery, Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, CA.
    Search for more papers by this author
  • Clare R. Gregory DVM, Diplomate ACVS,

    1. From the Comparative Transplantation Laboratory, Department of Surgical and Radiological Sciences, and Comparative Pathology Laboratory, School of Veterinary Medicine, University of California, Davis, CA; and Transplantation Immunology, Department of Cardiovascular Surgery, Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, CA.
    Search for more papers by this author
  • Stephen M. Griffey DVM, PhD,

    1. From the Comparative Transplantation Laboratory, Department of Surgical and Radiological Sciences, and Comparative Pathology Laboratory, School of Veterinary Medicine, University of California, Davis, CA; and Transplantation Immunology, Department of Cardiovascular Surgery, Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, CA.
    Search for more papers by this author
  • Joshua Jackson DVM, Diplomate ACVS,

    1. From the Comparative Transplantation Laboratory, Department of Surgical and Radiological Sciences, and Comparative Pathology Laboratory, School of Veterinary Medicine, University of California, Davis, CA; and Transplantation Immunology, Department of Cardiovascular Surgery, Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, CA.
    Search for more papers by this author
  • Lynda Bernsteen DVM, Diplomate ACVS,

    1. From the Comparative Transplantation Laboratory, Department of Surgical and Radiological Sciences, and Comparative Pathology Laboratory, School of Veterinary Medicine, University of California, Davis, CA; and Transplantation Immunology, Department of Cardiovascular Surgery, Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, CA.
    Search for more papers by this author
  • Randall E. Morris MD

    1. From the Comparative Transplantation Laboratory, Department of Surgical and Radiological Sciences, and Comparative Pathology Laboratory, School of Veterinary Medicine, University of California, Davis, CA; and Transplantation Immunology, Department of Cardiovascular Surgery, Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, CA.
    Search for more papers by this author

  • Supported by Hoechst Marion Roussel, Wiesbaden, Germany.

  • Presented at Transplant 2000, May 13–17, 2000, Chicago IL; the XVIII International Congress of the Transplantation Society, August 27-September 1, 2000, Rome, Italy; and the 35th Annual Scientific Meeting of the American College of Veterinary Surgeons, September 21–24, 2000, Crystal City, VA.

  • This work was performed at the University of California, Davis.

  • No reprints available.

Andrew E. Kyles, BVMS, PhD, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616.

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.

Ancillary