Adequacy of Initial Everolimus Dose, With and Without Calcineurin Inhibitors, in Kidney Transplant Recipients

This study investigates the adequacy of initial everolimus (EVR) dose, with and without calcineurin inhibitors (CNI), in kidney transplant recipients.

This retrospective cohort analysis involved data from 305 kidney transplant recipients participating in 3 randomized trials receiving reduced dose cyclosporin A (CsA) combined with EVR 0.75 mg BID (CSA/EVR0.75, N = 32) or 1.5 mg BID (CSA/EVR1.5, N = 31), reduced dose tacrolimus (TAC) combined with EVR 1.5 mg BID (TAC0.05/EVR1.5, N = 83), standard dose TAC combined with EVR 1.5 mg BID (TAC0.1/EVR1.5, N = 93), and EVR 1.5 mg BID (EVR1.5, N = 66) with TAC introduction after day 5. The adequacy of the initial EVR dose, based on EVR whole blood trough between 3 and 8 ng/mL, was compared using first EVR blood concentrations obtained at day 3 after transplantation.

Recipient age, proportion of patients with diabetes mellitus, and proportion of grafts from living donors were different among the groups. Dose-corrected EVR concentrations were higher in patients receiving CsA than in those receiving TAC or no calcineurin inhibitors (6.7 ± 5.9 versus 5.4 ± 2.2 versus 2.4 ± 0.8 versus 2.5 ± 0.9 versus 2.2 ± 0.7, P = 0.000). No differences were observed comparing dose adjusted EVR concentrations combined with TAC or alone (P = 0.073). The proportion of patients with EVR concentration below <3 ng/mL was lower when EVR was combined with CsA (25 versus 3 versus 43 versus 33 versus 50%, P = 0.000). Later introduction of TAC did not influence EVR concentrations. There were no differences in mean CsA concentrations comparing patients receiving EVR 0.75 or 1.5 mg BID (240 ± 143 versus 213 ± 105 ng/mL). On the other hand, mean TAC concentrations were higher according to the initial TAC dose regimen (6.4 ± 3.9 versus 9.8 ± 5.9 ng/mL).

In de novo kidney transplant recipients, the choice of the initial dose of EVR should consider the type of calcineurin inhibitor to reach target EVR concentration within the first week in a higher proportion of patients, maximizing the efficacy/toxicity profile.