TY - JOUR
T1 - Effect of initial immunosuppression on long-term kidney transplant outcome in immunological low-risk patients
AU - Michielsen, Laura A.
AU - van Zuilen, Arjan D.
AU - Verhaar, Marianne C.
AU - Wisse, Bram W.
AU - Kamburova, Elena G.
AU - Joosten, Irma
AU - Allebes, Wil A.
AU - van der Meer, Arnold
AU - Baas, Marije C.
AU - Spierings, Eric
AU - Hack, Cornelis E.
AU - van Reekum, Franka E.
AU - Bots, Michiel L.
AU - Drop, Adriaan C. A. D.
AU - Plaisier, Loes
AU - Seelen, Marc A. J.
AU - Sanders, Jan-Stephan F.
AU - Hepkema, Bouke G.
AU - Lambeck, Annechien J.
AU - Bungener, Laura B.
AU - Roozendaal, Caroline
AU - Tilanus, Marcel G. J.
AU - Voorter, Christien E.
AU - Wieten, Lotte
AU - van Duijnhoven, Elizabeth M.
AU - Gelens, Marielle A. C. J.
AU - Christiaans, Maarten H. L.
AU - van Ittersum, Frans J.
AU - Nurmohamed, Shaikh A.
AU - Lardy, Neubury M.
AU - Swelsen, Wendy
AU - van der Pant, Karlijn A.
AU - van der Weerd, Neelke C.
AU - ten Berge, Ineke J. M.
AU - Bemelman, Frederike J.
AU - Hoitsma, Andries
AU - van der Boog, Paul J. M.
AU - de Fijter, Johan W.
AU - Betjes, Michiel G. H.
AU - Heidt, Sebastiaan
AU - Roelen, Dave L.
AU - Claas, Frans H.
AU - Otten, Henderikus G.
AU - Hilbrands, Luuk B.
N1 - Funding Information:
This study was supported by research funding from the Dutch Kidney Foundation Project code CP12.23.
Funding Information:
The authors of this manuscript have conflicts of interests to disclose. L.A.M. is supported by an unrestricted research grant from Astellas pharma unrelated to this manuscript. E.S. is listed as inventor of a patent unrelated to this manuscript. A.D.v.Z. received personal fees from Astellas pharma, Novartis and Chiesi outside the manuscript. None of the other authors has any conflict of interest to disclose.
Publisher Copyright:
© 2018 The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
PY - 2019/8
Y1 - 2019/8
N2 - Background. Few studies have evaluated the effect of different immunosuppressive strategies on long-term kidney transplant outcomes. Moreover, as they were usually based on historical data, it was not possible to account for the presence of pretransplant donor-specific human-leukocyte antigen antibodies (DSA), a currently recognized risk marker for impaired graft survival. The aim of this study was to evaluate to what extent frequently used initial immunosuppressive therapies increase graft survival in immunological low-risk patients.Methods. We performed an analysis on the PROCARE cohort, a Dutch multicentre study including all transplantations performed in the Netherlands between 1995 and 2005 with available pretransplant serum (n = 4724). All sera were assessed for the presence of DSA by a luminex single-antigen bead assay. Patients with a previous kidney transplantation, pretransplant DSA or receiving induction therapy were excluded from the analysis.Results. Three regimes were used in over 200 patients: cyclosporine (CsA)/prednisolone (Pred) (n = 542), CsA/mycophenolate mofetil (MMF)/Pred (n = 857) and tacrolimus (TAC)/MMF/Pred (n = 811). Covariate-adjusted analysis revealed no significant differences in 10-year death-censored graft survival between patients on TAC/MMF/Pred therapy (79%) compared with patients on CsA/MMF/Pred (82%, P = 0.88) or CsA/Pred (79%, P = 0.21). However, 1-year rejection-free survival censored for death and failure unrelated to rejection was significantly higher for TAC/MMF/Pred (81%) when compared with CsA/MMF/Pred (67%, P<0.0001) and CsA/Pred (64%, P<0.0001).Conclusion. These results suggest that in immunological low-risk patients excellent long-term kidney graft survival can be achieved irrespective of the type of initial immunosuppressive therapy (CsA or TAC; with or without MMF), despite differences in 1-year rejection-free survival.
AB - Background. Few studies have evaluated the effect of different immunosuppressive strategies on long-term kidney transplant outcomes. Moreover, as they were usually based on historical data, it was not possible to account for the presence of pretransplant donor-specific human-leukocyte antigen antibodies (DSA), a currently recognized risk marker for impaired graft survival. The aim of this study was to evaluate to what extent frequently used initial immunosuppressive therapies increase graft survival in immunological low-risk patients.Methods. We performed an analysis on the PROCARE cohort, a Dutch multicentre study including all transplantations performed in the Netherlands between 1995 and 2005 with available pretransplant serum (n = 4724). All sera were assessed for the presence of DSA by a luminex single-antigen bead assay. Patients with a previous kidney transplantation, pretransplant DSA or receiving induction therapy were excluded from the analysis.Results. Three regimes were used in over 200 patients: cyclosporine (CsA)/prednisolone (Pred) (n = 542), CsA/mycophenolate mofetil (MMF)/Pred (n = 857) and tacrolimus (TAC)/MMF/Pred (n = 811). Covariate-adjusted analysis revealed no significant differences in 10-year death-censored graft survival between patients on TAC/MMF/Pred therapy (79%) compared with patients on CsA/MMF/Pred (82%, P = 0.88) or CsA/Pred (79%, P = 0.21). However, 1-year rejection-free survival censored for death and failure unrelated to rejection was significantly higher for TAC/MMF/Pred (81%) when compared with CsA/MMF/Pred (67%, P<0.0001) and CsA/Pred (64%, P<0.0001).Conclusion. These results suggest that in immunological low-risk patients excellent long-term kidney graft survival can be achieved irrespective of the type of initial immunosuppressive therapy (CsA or TAC; with or without MMF), despite differences in 1-year rejection-free survival.
KW - anti-HLA antibodies
KW - graft survival
KW - immunological low-risk
KW - immunosuppression
KW - kidney transplantation
KW - GRAFT-SURVIVAL
KW - RENAL-TRANSPLANTATION
KW - TACROLIMUS
KW - CYCLOSPORINE
KW - REJECTION
KW - MINIMIZATION
KW - NEPHROPATHY
KW - INFECTION
KW - FAILURE
KW - DISEASE
U2 - 10.1093/ndt/gfy377
DO - 10.1093/ndt/gfy377
M3 - Article
C2 - 30561730
SN - 0931-0509
VL - 34
SP - 1417
EP - 1422
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
IS - 8
ER -