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Efficacy and toxicity of a protocol using sirolimus, tacrolimus and daclizumab in a nonhuman primate renal allotransplant model.

Publication ,  Journal Article
Montgomery, SP; Mog, SR; Xu, H; Tadaki, DK; Hirshberg, B; Berning, JD; Leconte, J; Harlan, DM; Hale, D; Kirk, AD
Published in: Am J Transplant
April 2002

A regimen combining sirolimus, tacrolimus, and daclizumab has recently been shown to provide adequate immunosuppression for allogeneic islet transplantation in humans, but remains unproven for primarily vascularized allografts. We evaluated this regimen for renal allograft transplantation in mismatched nonhuman primates. Dosages of sirolimus and tacrolimus were adjusted for trough levels of 10-15 ng/mL and 4-6 ng/mL, respectively. Treated monkeys (n = 5) had significantly prolonged allograft survival, with a mean survival of 36 days vs. 7 days in untreated controls (n = 6, p = 0.008). Four of five treated animals, but none of the controls, developed fibrinoid vascular necrosis of the small intestine. A review of gut histology from animals on other immunosuppressive protocols performed by our laboratory suggested that these lesions were a result of sirolimus exposure. In summary, this regimen prolongs the survival of vascularized renal allografts, but is limited by profound GI toxicity in rhesus macaques.

Duke Scholars

Published In

Am J Transplant

DOI

ISSN

1600-6135

Publication Date

April 2002

Volume

2

Issue

4

Start / End Page

381 / 385

Location

United States

Related Subject Headings

  • Tacrolimus
  • Surgery
  • Sirolimus
  • Models, Animal
  • Macaca mulatta
  • Kidney Transplantation
  • Intestine, Small
  • Immunosuppressive Agents
  • Immunoglobulin G
  • Immune Tolerance
 

Citation

APA
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MLA
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Montgomery, S. P., Mog, S. R., Xu, H., Tadaki, D. K., Hirshberg, B., Berning, J. D., … Kirk, A. D. (2002). Efficacy and toxicity of a protocol using sirolimus, tacrolimus and daclizumab in a nonhuman primate renal allotransplant model. Am J Transplant, 2(4), 381–385. https://doi.org/10.1034/j.1600-6143.2002.20415.x
Montgomery, Sean P., Steven R. Mog, He Xu, Douglas K. Tadaki, Boaz Hirshberg, Justin D. Berning, John Leconte, David M. Harlan, Douglas Hale, and Allan D. Kirk. “Efficacy and toxicity of a protocol using sirolimus, tacrolimus and daclizumab in a nonhuman primate renal allotransplant model.Am J Transplant 2, no. 4 (April 2002): 381–85. https://doi.org/10.1034/j.1600-6143.2002.20415.x.
Montgomery SP, Mog SR, Xu H, Tadaki DK, Hirshberg B, Berning JD, et al. Efficacy and toxicity of a protocol using sirolimus, tacrolimus and daclizumab in a nonhuman primate renal allotransplant model. Am J Transplant. 2002 Apr;2(4):381–5.
Montgomery, Sean P., et al. “Efficacy and toxicity of a protocol using sirolimus, tacrolimus and daclizumab in a nonhuman primate renal allotransplant model.Am J Transplant, vol. 2, no. 4, Apr. 2002, pp. 381–85. Pubmed, doi:10.1034/j.1600-6143.2002.20415.x.
Montgomery SP, Mog SR, Xu H, Tadaki DK, Hirshberg B, Berning JD, Leconte J, Harlan DM, Hale D, Kirk AD. Efficacy and toxicity of a protocol using sirolimus, tacrolimus and daclizumab in a nonhuman primate renal allotransplant model. Am J Transplant. 2002 Apr;2(4):381–385.
Journal cover image

Published In

Am J Transplant

DOI

ISSN

1600-6135

Publication Date

April 2002

Volume

2

Issue

4

Start / End Page

381 / 385

Location

United States

Related Subject Headings

  • Tacrolimus
  • Surgery
  • Sirolimus
  • Models, Animal
  • Macaca mulatta
  • Kidney Transplantation
  • Intestine, Small
  • Immunosuppressive Agents
  • Immunoglobulin G
  • Immune Tolerance