Tacrolimus (Tac) is the most effective immunosuppressive agent to prevent acute allograft rejection. However, long-term transplant (Tx) outcomes are limited, at least in part, by its potential nephrotoxicity, which have led to the search for minimization strategies. We have previously demonstrated the short-term safety of a low dose Tac and Everolimus (Ev) regimen. We now report the long term outcomes of our strategy.

Methods:We conducted a prospective study in 40 adult kidney Tx recipients randomized to steroid free IS with low dose Tac and Ev or standard dose Tac and Mycophenolate Mofetil (MMF) after Alemtuzumab induction. Ev levels were maintained between 3-8ng/ml. Follow up included protocol biopsies at 3, 12, and 24 months, analysis of T cell populations in peripheral blood, and gene expression profiles. Primary outcomes were rejection free graft survival and eGFR.

Results:Baseline characteristics were similar in both groups. Mean follow up was 40±8 and 43±12 months (p=0.47) and mean Tac levels were 4.7±1.4 and 6.2±1.9ng/ml (p=0.01) in the Tac+Ev and Tac+MMF group respectively. Rejection free graft survival was greater in the Tac+Ev arm. Overall, eGFR, patient and graft survival, and incidence of adverse events, including proteinuria, were similar in both groups. The Ev+Tac combination induced expansion of CD4⁺CD25^hiFoxp3⁺regulatory T cells (Tregs)

Conclusion:Rejection free graft survival was greater in patients receiving low dose Tac+Ev compared to standard dose Tac+MMF, possibly related to Everolimus effect on Tregs. However, this did not translate into better allograft function or survival. Larger mechanistic studies and longer follow up are needed to define the role of this regimen post Tx.

CITATION INFORMATION: Kassis Y., Park S., Shetty A., Leventhal J., Mas V., Gallon L. Long Term Outcomes of a Steroid Free, Low Dose Tacrolimus with Everolimus Regimen in Kidney Transplant Am J Transplant. 2017;17 (suppl 3).

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