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

Author:

Michielsen Laura A1ORCID,van Zuilen Arjan D1,Verhaar Marianne C1,Wisse Bram W2,Kamburova Elena G2,Joosten Irma3,Allebes Wil A3,van der Meer Arnold3,Baas Marije C4,Spierings Eric2,Hack Cornelis E2,van Reekum Franka E1,Bots Michiel L5,Drop Adriaan C A D2,Plaisier Loes2,Seelen Marc A J6,Sanders Jan-Stephan F6,Hepkema Bouke G7,Lambeck Annechien J7,Bungener Laura B7,Roozendaal Caroline7,Tilanus Marcel G J8,Voorter Christien E8,Wieten Lotte8,van Duijnhoven Elizabeth M9,Gelens Mariëlle A C J9,Christiaans Maarten H L9,van Ittersum Frans J10,Nurmohamed Shaikh A10,Lardy Neubury M11,Swelsen Wendy11,van der Pant Karlijn A12,van der Weerd Neelke C12,ten Berge Ineke J M12,Bemelman Frederike J12,Hoitsma Andries13,van der Boog Paul J M14,de Fijter Johan W14,Betjes Michiel G H15,Heidt Sebastiaan16,Roelen Dave L16,Claas Frans H16,Otten Henderikus G2,Hilbrands Luuk B4

Affiliation:

1. Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

2. Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

3. Laboratory Medicine, Lab. Medical Immunology, Radboud University Medical Center, Nijmegen, The Netherlands

4. Radboud Institute for Health Sciences, Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands

5. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

6. Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

7. Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

8. Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands

9. Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center, Maastricht, The Netherlands

10. Department of Nephrology, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands

11. Department of Immunogenetics, Sanquin, Amsterdam, The Netherlands

12. Renal Transplant Unit, Department of Internal Medicine, Amsterdam UMC, Academic Medical Center, Amsterdam, The Netherlands

13. Dutch Organ Transplant Registry (NOTR), Dutch Transplant Foundation (NTS), Leiden, The Netherlands

14. Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands

15. Department of Nephrology, Erasmus Medical Center, Rotterdam, The Netherlands

16. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands

Abstract

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.

Funder

Dutch Kidney Foundation

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

Reference38 articles.

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2. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients;Am J Transplant,2009

3. Endorsement of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines on kidney transplantation: a European Renal Best Practice (ERBP) position statement;Heemann;Nephrol Dial Transplant,2011

4. Reduced exposure to calcineurin inhibitors in renal transplantation;Ekberg;N Engl J Med,2007

5. Calcineurin inhibitor minimization in the Symphony study: observational results 3 years after transplantation;Ekberg;Am J Transplant,2009

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