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

Sean P. Montgomery, Steven R. Mog, He Xu, Douglas K. Tadaki, Boaz Hirshberg, Justin D. Berning, John Leconte, David M. Harlan, Douglas Hale, Allan D. Kirk*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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 36days vs. 7days 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.

Original languageEnglish
Pages (from-to)381-385
Number of pages5
JournalAmerican Journal of Transplantation
Volume2
Issue number4
DOIs
StatePublished - Apr 2002
Externally publishedYes

Keywords

  • Allograft
  • Daclizumab
  • Kidney transplantation
  • Primate
  • Sirolimus
  • Tacrolimus

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