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Efficacy and Toxicity of a Protocol Using Sirolimus, Tacrolimus and Daclizumab in a Nonhuman Primate Renal Allotransplant Model
Author(s) -
Montgomery Sean P.,
Mog Steven R.,
Xu He,
Tadaki Douglas K.,
Hirshberg Boaz,
Berning Justin D.,
Leconte John,
Harlan David M.,
Hale Douglas,
Kirk Allan D.
Publication year - 2002
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1034/j.1600-6143.2002.20415.x
Subject(s) - daclizumab , sirolimus , medicine , tacrolimus , transplantation , regimen , immunosuppression , toxicity , urology , gastroenterology
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.