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To the Editor:

We agree with Rodríguez-Perálvarez et al. [1] that exposure to calcineurin inhibitors (CNIs) particularly in the early posttransplant phase may be critical for long-term renal function. In fact, a few years ago the ReSpECT study had suggested that a 5-day delay in introduction of tacrolimus after transplantation (vs. immediate start) has beneficial effects on renal function, which are still detectable after 1 year [2]. Especially in patients who suffer from impaired renal function already prior to transplantation (e.g. patients with high MELD scores), even longer delay in introduction of CNI treatment may be necessary and possible [3]. Another concept could be an even earlier tapering of CNIs (< 4 weeks) in combination with an mTOR inhibitor after transplantation.

Indeed, the CNI exposure of the patients during the run-in phase of our study may have been too high: immediately prior to randomization (at 4–6 weeks after transplantation) mean tacrolimus levels were around 10 ng/mL and mean cylosporin levels were around 215 ng/mL. Considering that all patients had received induction treatment with basiliximab, lower CNI levels early after transplantation should have been possible. Unfortunately, no detailed information on very early CNI levels after transplantation is available for our study. Therefore, future studies aiming at optimizing long-term renal function will need to focus much more on details of CNI treatment in the early postoperative phase. This includes a delay in CNI treatment as well as lower initial doses and/or early reduction of CNIs by combining it with an mTOR inhibitor very early after transplantation. These approaches are currently under evaluation in clinical trials in Germany.

Disclosure

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The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. H.S. received research support and honoraria as speaker and/or advisory board member from Novartis, Roche, Genzyme and BMS. M.M. is an employee of Novartis GmbH, Germany. L.F. received speaker's fee, research funding and travel grants as a member of advisory boards from Novartis; and received speaker's fee and travel grants from Astellas.

References

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