Calcineurin-Inhibitor Withdrawal vs. Minimization after Kidney Transplantation Is Safe but Does Not Improve Renal Function; 5-Year Results of a Prospective, Randomized Trial
Introduction - Trials of calcineurin-inhibitor (CI) withdrawal in kidney recipients have generally used control arms with high CI levels. More recent trials have demonstrated successful long term reduction of CI maintenance levels, but not necessarily compared to complete withdrawal. We compared CI withdrawal vs. minimization in a prospective randomized trial (Fig. 1).
Methods - After 6/mg/kg rATG induction (1 vs. 4 doses; rATG-S vs. rATG-D) and early steroid withdrawal, patients received tacrolimus/sirolimus vs. mycophenolate mofetil/sirolimus, with a tacrolimus target level at 6 months of 2-4 ng/ml.
Results - We enrolled 178 patients 19 to 65 years old with an average follow-up of 35.8+17.7 months including primary and re-transplants, with a primary endpoint of renal function and CAN (Table 1). Follow-up averaged 31.9+15.0 months in 65 patients withdrawn from CI; Group 3 (rATG-S) = 33, Group 4 (rATG-D) = 32. Patient survival, graft survival, and rejection did not change with CI withdrawal (p=0.09, 0.9, 0.85), but renal function was improved at 2 months (Fig 2C); however, the difference in renal function dissipated over time (Fig. 2A). The induction used has a greater impact on long-term renal function than the withdrawal status (Fig. 2B).
Conclusion - Although we successfully discontinued both CI and steroids with either rATG-S or rATG-D induction, only single-dose rATG induction independently and durably associated with improved renal function. Trials claiming a renal function beneﬁt after CI withdrawal should include comparison against CI minimization.
Stevens, R. B.,
Skorupa, J. Y.,
Rigley, T. H.,
Sandoz, J. P.,
Kellogg, A. M.,
Miller, N. R.,
Nielsen, K. J.,
Miles, C. D.,
& Wrenshall, L. E.
(2010). Calcineurin-Inhibitor Withdrawal vs. Minimization after Kidney Transplantation Is Safe but Does Not Improve Renal Function; 5-Year Results of a Prospective, Randomized Trial. American Journal of Transplantation, 10 (s4), 213-571.