Benefits of a loading dose of tacrolimus on graft survival of kidney transplants in nonhuman primates

Abstract

We examined the benefit of a loading dose of tacrolimus on the production of donor-specific antibodies (DSA), occurrence of acute rejection (AR) episodes, graft survival, and histological evidence of antibody-mediated rejection (ABMR) after kidney transplantation in nonhuman primates. Eight cynomolgus monkeys were assigned to two groups (n = 4 each): a maintenance dose-group, orally administered 1 mg/kg/day tacrolimus from the day of transplantation; and a loading-dose group, orally administered 2 mg/kg/day tacrolimus for 21 days after transplantation followed by 1 mg/kg/day. The monkeys were observed for up to 178 days after transplantation. Plasma creatinine was monitored over time. Recipients with increased plasma creatinine levels of >2 mg/dL received anti-acute rejection therapy. In the maintenance dose-group, DSA production, frequent AR episodes, and histological evidence of ABMR were observed in all recipients. Three of four recipients did not survive until the end of the observation period. In the loading-dose group, two recipients showed DSA production, frequent AR episodes and histological evidence of ABMR, while the remaining two had no DSA, AR episodes, or ABMR. Our findings indicate that a loading dose of tacrolimus may prevent DSA production, occurrence of AR events and ABMR, and prolong graft survival following kidney transplantation in monkeys.