Clinical Trial

. 2015 Jul 31:351:h3557.

doi: 10.1136/bmj.h3557.

Long term outcomes of transplantation using kidneys from expanded criteria donors: prospective, population based cohort study

Olivier Aubert¹, Nassim Kamar², Dewi Vernerey¹, Denis Viglietti³, Frank Martinez⁴, Jean-Paul Duong-Van-Huyen⁵, Dominique Eladari⁶, Jean-Philippe Empana¹, Marion Rabant⁷, Jerome Verine⁸, Lionel Rostaing², Nicolas Congy⁹, Céline Guilbeau-Frugier¹⁰, Georges Mourad¹¹, Valérie Garrigue¹¹, Emmanuel Morelon¹², Magali Giral¹³, Michèle Kessler¹⁴, Marc Ladrière¹⁴, Michel Delahousse¹⁵, Denis Glotz¹⁶, Christophe Legendre¹⁷, Xavier Jouven¹⁸, Carmen Lefaucheur¹⁶, Alexandre Loupy¹⁹

Affiliations

¹ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France.
² Department of Nephrology and Organ Transplantation, Rangueil, Toulouse, France INSERM U1043, Purpan, Toulouse Paul Sabatier University, Toulouse DIVAT (Données Informatiques VAlidées en Transplantation Network), France.
³ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris.
⁴ Department of Kidney Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Sorbonne Paris.
⁵ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Pathology, Necker Hospital, Paris.
⁶ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Renal Physiology, Georges Pompidou European Hospital, Paris.
⁷ Department of Pathology, Necker Hospital, Paris.
⁸ Department of Pathology, Saint-Louis Hospital, Paris.
⁹ Paul Sabatier University, Toulouse Molecular Immunogenetics Laboratory, EA 3034, Faculty of Medicine Purpan, IFR150 (INSERM), Toulouse, France Department of Immunology, Rangueil Hospital, Toulouse.
¹⁰ Paul Sabatier University, Toulouse Department of Pathology, Rangueil, Toulouse.
¹¹ DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Nephrology and Kidney Transplantation, Montpellier, France.
¹² DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Nephrology and Kidney Transplantation, Groupement Hospitalier, Hôpital Edouard Herriot, Lyon, France Centaure Network, France.
¹³ DIVAT (Données Informatiques VAlidées en Transplantation Network), France Centaure Network, France Department of Nephrology and Kidney Transplantation, Nantes, France.
¹⁴ DIVAT (Données Informatiques VAlidées en Transplantation Network), France Centaure Network, France Department of Nephrology and Kidney Transplantation, Nancy, France.
¹⁵ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Nephrology and Kidney Transplantation, Foch Hospital, Suresnes, Paris.
¹⁶ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris.
¹⁷ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Kidney Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Sorbonne Paris Centaure Network, France.
¹⁸ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Cardiology, Georges Pompidou European Hospital, Paris.
¹⁹ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Kidney Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Sorbonne Paris alexandreloupy@gmail.com.

PMID: 26232393
PMCID: PMC4521904
DOI: 10.1136/bmj.h3557

Clinical Trial

Long term outcomes of transplantation using kidneys from expanded criteria donors: prospective, population based cohort study

Olivier Aubert et al. BMJ. 2015.

. 2015 Jul 31:351:h3557.

doi: 10.1136/bmj.h3557.

Authors

Affiliations

¹ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France.
² Department of Nephrology and Organ Transplantation, Rangueil, Toulouse, France INSERM U1043, Purpan, Toulouse Paul Sabatier University, Toulouse DIVAT (Données Informatiques VAlidées en Transplantation Network), France.
³ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris.
⁴ Department of Kidney Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Sorbonne Paris.
⁵ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Pathology, Necker Hospital, Paris.
⁶ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Renal Physiology, Georges Pompidou European Hospital, Paris.
⁷ Department of Pathology, Necker Hospital, Paris.
⁸ Department of Pathology, Saint-Louis Hospital, Paris.
⁹ Paul Sabatier University, Toulouse Molecular Immunogenetics Laboratory, EA 3034, Faculty of Medicine Purpan, IFR150 (INSERM), Toulouse, France Department of Immunology, Rangueil Hospital, Toulouse.
¹⁰ Paul Sabatier University, Toulouse Department of Pathology, Rangueil, Toulouse.
¹¹ DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Nephrology and Kidney Transplantation, Montpellier, France.
¹² DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Nephrology and Kidney Transplantation, Groupement Hospitalier, Hôpital Edouard Herriot, Lyon, France Centaure Network, France.
¹³ DIVAT (Données Informatiques VAlidées en Transplantation Network), France Centaure Network, France Department of Nephrology and Kidney Transplantation, Nantes, France.
¹⁴ DIVAT (Données Informatiques VAlidées en Transplantation Network), France Centaure Network, France Department of Nephrology and Kidney Transplantation, Nancy, France.
¹⁵ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Nephrology and Kidney Transplantation, Foch Hospital, Suresnes, Paris.
¹⁶ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris.
¹⁷ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Kidney Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Sorbonne Paris Centaure Network, France.
¹⁸ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France Department of Cardiology, Georges Pompidou European Hospital, Paris.
¹⁹ Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, Paris Descartes University, 75015 Paris, France DIVAT (Données Informatiques VAlidées en Transplantation Network), France Department of Kidney Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Sorbonne Paris alexandreloupy@gmail.com.

PMID: 26232393
PMCID: PMC4521904
DOI: 10.1136/bmj.h3557

Abstract

Objectives: To assess the long term outcomes of transplantation using expanded criteria donors (ECD; donors aged ≥ 60 years or aged 50-59 years with vascular comorbidities) and assess the main determinants of its prognosis.

Design: Prospective, population based cohort study.

Setting: Four French referral centres.

Participants: Consecutive patients who underwent kidney transplantation between January 2004 and January 2011, and were followed up to May 2014. A validation cohort included patients from another four referral centres in France who underwent kidney transplantation between January 2002 and December 2011.

Main outcome measures: Long term kidney allograft survival, based on systematic assessment of donor, recipient, and transplant clinical characteristics; preimplantation biopsy; and circulating levels of donor specific anti-HLA (human leucocyte antigen) antibody (DSA) at baseline.

Results: The study included 6891 patients (2763 in the principal cohort, 4128 in the validation cohort). Of 2763 transplantations performed, 916 (33.2%) used ECD kidneys. Overall, patients receiving ECD transplants had lower allograft survival after seven years than patients receiving transplants from standard criteria donors (SCD; 80% v 88%, P<0.001). Patients receiving ECD transplants who presented with circulating DSA at the time of transplantation had worse allograft survival after seven years than patients receiving ECD kidneys without circulating DSA at transplantation (44% v 85%, P < 0.001). After adjusting for donor, recipient, and transplant characteristics, as well as preimplantation biopsy findings and baseline immunological parameters, the main independent determinants of long term allograft loss were identified as allocation of ECDs (hazard ratio 1.84 (95% confidence interval 1.5 to 2.3); P < 0.001), presence of circulating DSA on the day of transplantation (3.00 (2.3 to 3.9); P < 0.001), and longer cold ischaemia time (> 12 h; 1.53 (1.1 to 2.1); P = 0.011). Recipients of ECD kidneys with circulating DSA showed a 5.6-fold increased risk of graft loss compared with all other transplant therapies (P < 0.001). ECD allograft survival at seven years significantly improved with screening and transplantation in the absence of circulating DSA (P < 0.001) and with shorter (<12 h) cold ischaemia time (P=0.030), respectively. This strategy achieved ECD graft survival comparable to that of patients receiving an SCD transplant overall, translating to a 544.6 allograft life years saved during the nine years of study inclusion time.

Conclusions: Circulating DSA and cold ischaemia time are the main independent determinants of outcome from ECD transplantation. Allocation policies to avoid DSA and reduction of cold ischaemia time to increase efficacy could promote wider implement of ECD transplantation in the context of organ shortage and improve its prognosis.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work, no financial relationships with any organisations that might have an interest in the submitted work in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

Figures

None — Kaplan-Meier curves of kidney allograft survival by (A) donor type and (B) presence of DSA on the day of transplantation. Panel A shows the classic approach to determine kidney allograft survival based on donor status (that is, SCD or ECD). Panel B integrates donor status with the presence or absence of DSA on the day of transplantation. SCD=standard criteria donor; ECD=expanded criteria donor; DSA=donor specific anti-HLA antibodies; SCD/DSA−=patients receiving SCD transplants without DSA; SCD/DSA+=patients receiving SCD transplants with DSA; ECD/DSA−=patients receiving ECD transplants without DSA; ECD/DSA+=patients receiving ECD transplants with DSA; HR=hazard ratio

See this image and copyright information in PMC

Comment in

Marginal kidneys for transplantation.
Chapman JR. Chapman JR. BMJ. 2015 Aug 3;351:h3856. doi: 10.1136/bmj.h3856. BMJ. 2015. PMID: 26239226 No abstract available.
Transplantation: Optimizing ECD graft outcomes.
Carney EF. Carney EF. Nat Rev Nephrol. 2015 Oct;11(10):567. doi: 10.1038/nrneph.2015.143. Epub 2015 Aug 18. Nat Rev Nephrol. 2015. PMID: 26281894 No abstract available.

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Long term outcomes of transplantation using kidneys from expanded criteria donors: prospective, population based cohort study

Affiliations

Long term outcomes of transplantation using kidneys from expanded criteria donors: prospective, population based cohort study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

Publication types

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LinkOut - more resources

Full Text Sources

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Medical

Research Materials