Pippias, M., Jager, K. J., Caskey, F., Casula, A., Erlandsson, H., Finne, P., ... Stel, V. S. (2018). Kidney transplant outcomes from older deceased donors: a paired kidney analysis by the European Renal Association–European Dialysis and Transplant Association Registry. Transplant International, 31(7), 708-719. https://doi.org/10.1111/tri.13103 Peer reviewed version License (if available): Unspecified Link to published version (if available): 10.1111/tri.13103 Link to publication record in Explore Bristol Research PDF-document This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Wiley at https://onlinelibrary.wiley.com/doi/abs/10.1111/tri.13103 . Please refer to any applicable terms of use of the publisher. University of Bristol - Explore Bristol Research General rights This document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms brought to you by CORE View metadata, citation and similar papers at core.ac.uk provided by Explore Bristol Research
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Pippias, M., Jager, K. J., Caskey, F., Casula, A., Erlandsson, H., Finne, P., ...Stel, V. S. (2018). Kidney transplant outcomes from older deceased donors: apaired kidney analysis by the European Renal Association–EuropeanDialysis and Transplant Association Registry. Transplant International,31(7), 708-719. https://doi.org/10.1111/tri.13103
Peer reviewed version
License (if available):Unspecified
Link to published version (if available):10.1111/tri.13103
Link to publication record in Explore Bristol ResearchPDF-document
This is the author accepted manuscript (AAM). The final published version (version of record) is available onlinevia Wiley at https://onlinelibrary.wiley.com/doi/abs/10.1111/tri.13103 . Please refer to any applicable terms of useof the publisher.
University of Bristol - Explore Bristol ResearchGeneral rights
This document is made available in accordance with publisher policies. Please cite only the publishedversion using the reference above. Full terms of use are available:http://www.bristol.ac.uk/pure/about/ebr-terms
brought to you by COREView metadata, citation and similar papers at core.ac.uk
Table 4 Mean number of functioning graft years (95% confidence interval) for the group 1 and
group 2 younger and older recipients respectively. Adjusted for cold ischaemia time and
human leukocyte antigen mismatch. Differences highlighted in bold indicate a significant
difference (p<0.05).
22
Table 5 Relative risk (RR) of death-censored graft failure, graft failure and patient mortality for
the group 1 and group 2 younger recipient groups as compared to their paired older
recipients. *Adjusted for cold ischaemia time and human leukocyte antigen (HLA) mismatch.
** Adjusted for cold ischaemia time, HLA mismatch, recipient sex, primary renal disease and
initial modality of renal replacement therapy. Differences highlighted in bold indicate a
significant difference (p<0.05).
23
References 1. Wu DA, Watson CJ, Bradley JA, Johnson RJ, Forsythe JL, Oniscu GC. Global trends and challenges in deceased donor kidney allocation. Kidney Int. 2017;91(6):1287-99. 2. Kidney Transplantation: Deceased Donor Organ Allocation http://wwwodtnhsuk/pdf/kidney_allocation_policypdf
4, last accessed 23.09.2015. 3. Akoh JA, Rana TA. Impact of donor age on outcome of kidney transplantation from controlled donation after cardiac death. Saudi J Kidney Dis Transpl. 2013;24(4):673-81. 4. Keith DS, Demattos A, Golconda M, Prather J, Norman D. Effect of donor recipient age match on survival after first deceased donor renal transplantation. Journal of the American Society of Nephrology : JASN. 2004;15(4):1086-91. 5. Lim WH, Chang S, Chadban S, Campbell S, Dent H, Russ GR, et al. Donor-recipient age matching improves years of graft function in deceased-donor kidney transplantation. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2010;25(9):3082-9. 6. Pascual J, Zamora J, Pirsch JD. A systematic review of kidney transplantation from expanded criteria donors. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2008;52(3):553-86. 7. Oppenheimer F, Aljama P, Asensio Peinado C, Bustamante Bustamante J, Crespo Albiach JF, Guirado Perich L. The impact of donor age on the results of renal transplantation. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2004;19 Suppl 3:iii11-5. 8. de Fijter JW. Counselling the elderly between hope and reality. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2011;26(7):2079-81. 9. Eurotransplant. Annual report 2015. https://wwweurotransplantorg/cms/mediaobjectphp?file=AR_ET_20153pdf. Accessed 22nd June 2016. 10. Scandiatransplant. Annual Report 2014. http://wwwscandiatransplantorg/resources/AnnualScandiatransplantdatareport2014pdf. 2015. 11. Pippias M, Jager KJ, Kramer A, Leivestad T, Sanchez MB, Caskey FJ, et al. The changing trends and outcomes in renal replacement therapy: data from the ERA-EDTA Registry. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2015. 12. Zhang X. Comparison of restricted mean survival times between treatments based on a stratified Cox model. Bio-Algorithms and Med-Systems. 2013; 9(4):183–9. 13. Heinzl H, Kaider A. Gaining more flexibility in Cox proportional hazards regression models with cubic spline functions. Computer methods and programs in biomedicine. 1997;54(3):201-8. 14. Royston P, Parmar MK. Restricted mean survival time: an alternative to the hazard ratio for the design and analysis of randomized trials with a time-to-event outcome. BMC Med Res Methodol. 2013;13:152. 15. Noordzij M, Leffondre K, van Stralen KJ, Zoccali C, Dekker FW, Jager KJ. When do we need competing risks methods for survival analysis in nephrology? Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2013;28(11):2670-7. 16. Transplantation EEGoR. European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.13 Analysis of patient and graft survival.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2002;17 Suppl 4:60-7. 17. Couchoud C, Dantony E, Elsensohn MH, Villar E, Vigneau C, Moranne O, et al. Restricted mean survival time over 15 years for patients starting renal replacement therapy. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2017;32(suppl_2):ii60-ii7. 18. Waiser J, Schreiber M, Budde K, Fritsche L, Bohler T, Hauser I, et al. Age-matching in renal transplantation. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2000;15(5):696-700. 19. de Fijter JW. The impact of age on rejection in kidney transplantation. Drugs & aging. 2005;22(5):433-49. 20. Curschellas E, Landmann J, Durig M, Huser B, Kyo M, Basler V, et al. Morphologic findings in "zero-hour" biopsies of renal transplants. Clinical nephrology. 1991;36(5):215-22. 21. Melk A, Schmidt BM, Braun H, Vongwiwatana A, Urmson J, Zhu LF, et al. Effects of donor age and cell senescence on kidney allograft survival. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2009;9(1):114-23. 22. Woo YM, Gill JS, Johnson N, Pereira BJ, Hariharan S. The advanced age deceased kidney donor: current outcomes and future opportunities. Kidney Int. 2005;67(6):2407-14. 23. Tullius SG, Tran H, Guleria I, Malek SK, Tilney NL, Milford E. The combination of donor and recipient age is critical in determining host immunoresponsiveness and renal transplant outcome. Ann Surg. 2010;252(4):662-74. 24. Martinez-Vaquera S, Navarro Cabello MD, Lopez-Andreu M, Jurado JM, Haad CR, Salas RO, et al. Outcomes in renal transplantation with expanded-criteria donors. Transplantation proceedings. 2013;45(10):3595-8. 25. Ma MK, Lim WH, Craig JC, Russ GR, Chapman JR, Wong G. Mortality among Younger and Older Recipients of Kidney Transplants from Expanded Criteria Donors Compared with Standard Criteria Donors. Clinical journal of the American Society of Nephrology : CJASN. 2016;11(1):128-36.
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Table 1 Additional data sources and number of recipients provided by country or region
Country / Region supplying data
Data source(s) Number of recipients
Proportion (%)
Austria Austrian dialysis and transplant registry 90 6.4
Basque country (Spain)
Information unit about renal patients from the Basque Country
58 4.1
Catalonia (Spain) Catalan Renal Registry, Catalan Transplant Organization, Health Department, Generalitat of Catalonia
182 12.9
Denmark Danish Renal Registry and Scandiatransplant 46 3.3
Finland Finnish Registry for Kidney Diseases and the Finnish Kidney Transplant Registry
96 6.8
the Netherlands Dutch transplant foundation 138 9.8
Norway Norwegian Renal Registry 38 2.7
Sweden Swedish Renal Registry and Scandiatransplant 96 6.8
United Kingdom United Kingdom Renal Registry and UK Transplant Registry held by NHS Blood and Transplant
666 47.2
Total 1410 100
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Table 2 Overview of the different types of survival analyses used in this paper. The adjustments were made in a step-wise manner; (1) transplant related parameters influencing graft survival, i.e. cold ischaemia time (CIT) and human leukocyte antigen mismatch (HLA MM) and (2) recipient factors influencing graft survival, i.e. recipient sex, primary renal disease and initial modality of renal replacement therapy.
Survival analysis outcome Survival analysis method Starting point Event of interest Competing event Censoring observations Variables adjusted for
Cumulative risk of graft failure
Cumulative incidence competing risk method
Date of kidney transplant
Graft failure Death with a functioning graft*
End of follow-up period Loss to follow-up
Restricted mean number of functioning graft years
Area under the estimated graft survival function
Date of kidney transplant
Graft failure or Death with a functioning graft
End of follow-up period or End of 10 year follow-up; whichever event occurred first Loss to follow-up
CIT, HLA MM
Relative risk of death-censored graft failure between paired recipients
Graft failure Death with a functioning graft** End of follow-up period Loss to follow-up
1. CIT & HLA MM. 2. CIT, HLA MM, recipient sex, PRD & first RRT modality
Relative risk of graft failure between paired recipients
Pair-stratified Cox regression
Date of kidney transplant
Graft failure or Death with a functioning graft
End of follow-up period Loss to follow-up
1. CIT & HLA MM. 2. CIT, HLA MM, recipient sex, PRD & first RRT modality
Relative risk of mortality between paired recipients
Pair-stratified Cox regression
Date of kidney transplant
Patient death End of follow-up period Loss to follow-up
1. CIT & HLA MM. 2. CIT, HLA MM, recipient sex, PRD & first RRT modality
HLA MM: human leukocyte antigen mismatch. CIT: cold ischaemia time. PRD: primary renal disease. RRT: renal replacement therapy. End of follow-up period: 31st December 2013 * Using the cumulative incidence competing risk method, “death with a functioning graft” was interpreted as a competing event. **Using the pair-stratified cause-specific Cox regression, “death with a functioning graft” was interpreted as a censored event (15)
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Table 3 Baseline characteristics of the group 1 and group 2 younger recipients and their paired older recipients and the corresponding donor details. (RRT: Renal replacement therapy. HLA: human leukocyte antigen mismatch [favourable HLA-A, HLA-B and HLA-DR mismatches: 000, 100, 010, 110]. IQR: inter-quartile range)
Total follow-up time, years 2228.20 2092.23 2571.47 2372.33
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Table 4 Mean number of functioning graft years (95% confidence interval) for the group 1 and group 2 younger and older recipients respectively. Adjusted for cold ischaemia time and human leukocyte antigen mismatch. Differences highlighted in bold indicate a significant difference (p<0.05).
Group 1 Group 2
Follow-up time restricted to:
Mean number of functioning graft years for the younger recipients and the paired older recipients
Mean number of functioning graft years for the younger recipients and the paired older recipients
Based on deceased donors with a median age of 61 (interquartile range, 58-65)
Based on deceased donors with a median age of 60 (interquartile range, 57-63)
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Table 5 Relative risk (RR) of death-censored graft failure, graft failure and patient mortality for the group 1 and group 2 younger recipient groups as compared to their paired older recipients. *Adjusted for cold ischaemia time and human leukocyte antigen (HLA) mismatch. ** Adjusted for cold ischaemia time, HLA mismatch, recipient sex, primary renal disease and initial modality of renal replacement therapy. Differences highlighted in bold indicate a significant difference (p<0.05).
Group 1 younger recipients compared to paired older recipients
Group 2 younger recipients compared to paired older recipients