Effect of initial immunosuppression on long-term kidney transplant outcome in immunological low-risk patients

Laura A. Michielsen, Arjan D. van Zuilen, Marianne C. Verhaar, Bram W. Wisse, Elena G. Kamburova, Irma Joosten, Wil A. Allebes, Arnold van der Meer, Marije C. Baas, Eric Spierings, Cornelis E. Hack, Franka E. van Reekum, Michiel L. Bots, Adriaan C. A. D. Drop, Loes Plaisier, Marc A. J. Seelen, Jan-Stephan F. Sanders, Bouke G. Hepkema, Annechien J. Lambeck, Laura B. BungenerCaroline Roozendaal, Marcel G. J. Tilanus, Christien E. Voorter, Lotte Wieten, Elizabeth M. van Duijnhoven, Mariëlle A. C. J. Gelens, Maarten H. L. Christiaans, Frans J. van Ittersum, Shaikh A. Nurmohamed, Neubury M. Lardy, Wendy Swelsen, Karlijn A. van der Pant, Neelke C. van der Weerd, Ineke J. M. ten Berge, Frederike J. Bemelman, Andries Hoitsma, Paul J. M. van der Boog, Johan W. de Fijter, Michiel G. H. Betjes, Sebastiaan Heidt, Dave L. Roelen, Frans H. Claas, Henderikus G. Otten, Luuk B. Hilbrands

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Abstract

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.
Original languageEnglish
Pages (from-to)1417-1422
JournalNephrology, Dialysis, Transplantation
Volume34
Issue number8
DOIs
Publication statusPublished - 2019

Cite this

Michielsen, L. A., van Zuilen, A. D., Verhaar, M. C., Wisse, B. W., Kamburova, E. G., Joosten, I., Allebes, W. A., van der Meer, A., Baas, M. C., Spierings, E., Hack, C. E., van Reekum, F. E., Bots, M. L., Drop, A. C. A. D., Plaisier, L., Seelen, M. A. J., Sanders, J-S. F., Hepkema, B. G., Lambeck, A. J., ... Hilbrands, L. B. (2019). Effect of initial immunosuppression on long-term kidney transplant outcome in immunological low-risk patients. Nephrology, Dialysis, Transplantation, 34(8), 1417-1422. https://doi.org/10.1093/ndt/gfy377