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Renal function to 5 years after late conversion of kidney transplant patients to everolimus: a randomized trial

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Abstract

Background

Few trials have investigated late preemptive conversion of kidney transplant patients from a calcineurin inhibitor (CNI) to an mTOR inhibitor.

Methods

In an open-label, 12-month, prospective, randomized, parallel-group study, maintenance kidney transplant patients (>6 months post-transplant) either switched from CNI to everolimus or continued their current CNI regimen. Patients who completed the core study were followed to 5 years post-randomization.

Results

Of 93 randomized patients, 78 completed the core study and 67 attended the final 60-month study visit. Mean time post-transplant at baseline was 82.6 months and 70.5 months in the everolimus and CNI groups, respectively. At month 60, adjusted mean eGFR (Nankivell) was 63.0 (95 % CI 57.8, 68.2) mL/min/1.73 m2 in the everolimus group versus 57.9 (95 % CI 52.6, 63.1) mL/min/1.73 m2 in the CNI group, a difference of 5.1 (95 % CI −0.6, 10.8) mL/min/1.73 m2 (p = 0.076). Among patients who remained on randomized study drug at month 60, mean eGFR (Nankivell) was 71.6 (95 % CI 64.2, 79.0) mL/min/1.73 m2 in everolimus-treated patients (n = 21) versus 60.6 (95 % CI 55.1, 66.1) mL/min/1.73 m2 in CNI-treated patients (n = 29) (mean difference 11.0; 95 % CI 3.6, 18.5 mL/min/1.73 m2; p = 0.005). No cases of BPAR occurred from randomization to month 60 in either group. Graft loss occurred in three everolimus-treated patients and one CNI-treated patient. No unexpected safety concerns were observed in either group.

Conclusion

Late preemptive conversion of maintenance kidney transplant patients from CNI to everolimus may be associated with improved long-term renal function and preserves immunosuppressive efficacy. Patient numbers were low, but these findings merit further investigation.

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Acknowledgments

The authors would like to thank Caroline Dunstall for editorial support and Elisabeth Grünewald for support on statistical analyses. The study was funded by Novartis Pharma GmbH, Nuernberg, Germany.

Conflict of interest

Klemens Budde has had a consultancy agreement and travel support from BMS, Chiesi, Novartis, Hexal, Pfizer, Veloxis and Effimune, grant/research support and speaker’s/study honoraria from BMS, Chiesi, Novartis, Hexal, Pfizer and Veloxis and grant/research/travel support and speaker’s/study fees from Siemens, AiCuris, Astellas, BmT GmbH and Roche; Claudia Sommerer has provided research support to Novartis, Teva and Astellas; Thomas Rath has received grant/research support from Novartis and Roche and speaker’s fees and honoraria from Novartis, Roche, Teva and Astellas; Petra Reinke has no conflicts of interest to declare; Hermann Haller has been a consultant for Novartis, Genzyme, Roche, Sanofi-Aventis, Noxxon, MedWiss, Alexion, Phenos and MSD and received speaker’s honoraria from and chaired meetings for Amgen, Astra-Zeneca, Alexion, Recordati, Menarini, Novartis, Genzyme, Roche, Otsuka, Pfizer, Bayer-Schering, Sanofi-Aventis, Noxxon, MedWiss, Phenos, MSD, Bristol-Myers Squibb and CVRx; Oliver Witzke has received research grants for clinical studies, speaker’s fees, honoraria and travel expenses from Amgen, Astellas, Bristol-Myers Squibb, Chiesi, Novartis, Roche, Pfizer and Sanofi; Barbara Suwelack has received study honoraria, speaker’s fees and research support from Novartis, Astellas and BMS; Daniel Baeumer, Christian Sieder and Martina Porstner are full time employees of Novartis; Wolfgang Arns has received study honoraria from Novartis, BMS, Roche and Astellas.

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Correspondence to Wolfgang Arns.

Additional information

For the APOLLO Study Group. The members of the APOLLO Study Group are listed in Appendix.

Appendix: The APOLLO Study Group

Appendix: The APOLLO Study Group

Wolfgang Arns, Cologne; Klemens Budde, Berlin; Hermann Haller, Hannover; Katharina Heller, Erlangen; Thomas Rath, Kaiserslautern; Petra Reinke, Berlin; Lutz Renders, Kiel; Michael Schoemig, Heilbronn; Barbara Suwelack, Muenster; Frank Pietruck and Oliver Witzke, Essen; Martin Zeier and Claudia Sommerer, Heidelberg. All centers were in Germany.

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Budde, K., Sommerer, C., Rath, T. et al. Renal function to 5 years after late conversion of kidney transplant patients to everolimus: a randomized trial. J Nephrol 28, 115–123 (2015). https://doi.org/10.1007/s40620-014-0134-4

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  • DOI: https://doi.org/10.1007/s40620-014-0134-4

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