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 Bungener, Caroline 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

Published: 01/08/2019


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.

Full Access Link: Nephrology Dialysis Transplantation