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Five‐year outcomes in kidney transplant patients randomized to everolimus with cyclosporine withdrawal or low‐exposure cyclosporine versus standard therapy
Author(s) -
Sommerer Claudia,
Duerr Michael,
Witzke Oliver,
Lehner Frank,
Arns Wolfgang,
Kliem Volker,
Ackermann Daniel,
Guba Markus,
Jacobi Johannes,
Hauser Ingeborg A.,
Stahl Rolf,
Reinke Petra,
Rath Thomas,
Veit Justyna,
Mehrabi Arianeb,
Porstner Martina,
Budde Klemens
Publication year - 2018
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14897
Subject(s) - medicine , everolimus , calcineurin , urology , regimen , immunosuppression , randomized controlled trial , transplantation , renal function , kidney transplantation , surgery
HERAKLES was a 1‐year randomized, multicenter trial. Patients were randomized at 3 months after kidney transplantation to remain on cyclosporine‐based therapy, switch to everolimus without a calcineurin inhibitor ( CNI ), or switch to everolimus with low‐exposure cyclosporine. Overall, 417 of 497 (83.9%) patients from the core study entered a 4‐year extension study. The randomized regimen was continued to year 5 in 75.9%, 41.9% and 24.6% of patients in the standard‐ CNI , CNI ‐free and low‐ CNI groups, respectively. Adjusted estimated GFR at year 5 was significantly higher in the CNI ‐free group versus standard CNI (difference 7.2 mL /min/1.73 m 2 , P < .001) or low CNI (difference 7.6 mL /min/1.73 m 2 , P < .001). For patients who continued randomized therapy for 5 years, differences were 14.4 mL /min/1.73 m 2 and 10.1 mL /min/1.73 m 2 , respectively. Biopsy‐proven acute rejection occurred during the 4‐year extension study in 7.6%, 8.6%, and 9.0% of patients in the standard‐ CNI , CNI ‐free and low‐ CNI groups, respectively ( P = .927). In conclusion, conversion to a CNI ‐free everolimus regimen 3 months after kidney transplantation improved long‐term graft function, particularly in patients who continued the CNI ‐free regimen. Low CNI with everolimus did not improve renal function. Efficacy was comparable between groups but frequent immunosuppression changes should be taken into account.