Dataset Information

Impact of targeted hypothermia in expanded-criteria organ donors on recipient kidney-graft function: study protocol for a multicentre randomised controlled trial (HYPOREME).

ABSTRACT:

Introduction

Expanded-criteria donors (ECDs) are used to reduce the shortage of kidneys for transplantation. However, kidneys from ECDs are associated with an increased risk of delayed graft function (DGF), a risk factor for allograft loss and mortality. HYPOREME will be a multicentre randomised controlled trial (RCT) comparing targeted hypothermia to normothermia in ECDs, in a country where the use of machine perfusion for organ storage is the standard of care. We hypothesise that hypothermia will decrease the incidence of DGF.

Methods and analysis

HYPOREME is a multicentre RCT comparing the effect on kidney function in recipients of targeted hypothermia (34°C-35°C) and normothermia (36.5°C-37.5°C) in the ECDs. The temperature intervention starts from randomisation and is maintained until aortic clamping in the operating room. We aim to enrol 289 ECDs in order to analyse the kidney function of 516 recipients in the 53 participating centres. The primary outcome is the occurrence of DGF in kidney recipients, defined as a requirement for renal replacement therapy within 7 days after transplantation (not counting a single session for hyperkalemia during the first 24 hours). Secondary outcomes include the proportion of patients with individual organs transplanted in each group; the number of organs transplanted from each ECD and the vital status and kidney function of the recipients 7 days, 28 days, 3 months and 1 year after transplantation. An interim analysis is planned after the enrolment of 258 kidney recipients.

Ethics and dissemination

The trial was approved by the ethics committee of the French Intensive Care Society (CE-SRLF-16-07) on 26 April 2016 and by the competent French authorities on 20 April 2016 (Comité de Protection des Personnes-TOURS-Région Centre-Ouest 1, registration #2016-S3). Findings will be published in peer-reviewed journals and presented during national and international scientific meetings.

Trial registration number

NCT03098706.

SUBMITTER: Brule N

PROVIDER: S-EPMC8961135 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Impact of targeted hypothermia in expanded-criteria organ donors on recipient kidney-graft function: study protocol for a multicentre randomised controlled trial (HYPOREME).

Brulé Noëlle N Canet Emmanuel E Péré Morgane M Feuillet Fanny F Hourmant Maryvonne M Asehnoune Karim K Rozec Bertrand B Duveau Agnes A Dube Laurent L Pierrot Marc M Humbert Stanislas S Tirot Patrice P Boyer Jean-Marc JM Martin-Lefevre Laurent L Labadie François F Robert René R Benard Thierry T Kerforne Thomas T Thierry Antoine A Lesieur Olivier O Vincent Jean-François JF Lesouhaitier Mathieu M Larmet Raphaelle R Vigneau Cecile C Goepp Angelique A Bouju Pierre P Quentin Charlotte C Egreteau Pierre-Yves PY Huet Olivier O Renault Anne A Le Meur Yannick Y Venhard Jean-Christophe JC Buchler Mathias M Michel Olivier O Voellmy Marie-Hélène MH Herve Fabien F Schnell David D Courte Anne A Glotz Denis D Amrouche Lucile L Hazzan Marc M Kamar Nassim N Moal Valerie V Bourenne Jeremy J Le Quintrec-Donnette Moglie M Morelon Emmanuel E Boulain Thierry T Grimbert Philippe P Heng Anne Elisabeth AE Merville Pierre P Garin Aude A Hiesse Christian C Fermier Brice B Mousson Christiane C Guyot-Colosio Charlotte C Bouvier Nicolas N Rerolle Jean-Philippe JP Durrbach Antoine A Drouin Sarah S Caillard Sophie S Frimat Luc L Girerd Sophie S Albano Laetitia L Rostaing Lionel L Bertrand Dominique D Hertig Alexandre A Westeel Pierre-Francois PF Montini Florent F Delpierre Eric E Dorez Dider D Alamartine Eric E Ouisse Carole C Sebille Veronique V Reignier Jean J

BMJ open 20220328 3

<h4>Introduction</h4>Expanded-criteria donors (ECDs) are used to reduce the shortage of kidneys for transplantation. However, kidneys from ECDs are associated with an increased risk of delayed graft function (DGF), a risk factor for allograft loss and mortality. HYPOREME will be a multicentre randomised controlled trial (RCT) comparing targeted hypothermia to normothermia in ECDs, in a country where the use of machine perfusion for organ storage is the standard of care. We hypothesise that hypot ...[more]

PMID: 35351701

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Project description:Background and objectivesThe broader use of combined expanded criteria donor and donation after circulatory death (ECD/DCD) kidneys may help expand the deceased donor pool. The purpose of our study was to evaluate discard rates of kidneys from ECD/DCD donors and factors associated with discard.Design, setting, participants, & measurementsECD/DCD donors and kidneys were evaluated from January 1, 2000 to March 31, 2011 using data from the Scientific Registry of Transplant Recipients. The kidney donor risk index was calculated for all ECD/DCD kidneys. Multivariable logistic regression models were used to determine risk factors for discarding both donor kidneys. The Kaplan-Meier product limit method and the log-rank statistic were used to assess the cumulative probability of graft failure for transplants from ECD/DCD donors where the mate kidney was discarded versus both kidneys were used.ResultsThere were 896 ECD/DCD donors comprising 1792 kidneys. Both kidneys were discarded in 44.5% of donors, whereas 51.0% of all available kidneys were discarded. The kidney donor risk index scores were higher among donors of discarded versus transplanted kidneys (median, 1.82; interquartile range, 1.60, 2.07 versus median, 1.67; interquartile range, 1.49, 1.87, respectively; P<0.001); however, the distributions showed considerable overlap. The adjusted odds ratios for discard were higher among donors who were older, diabetic, AB blood type, and hepatitis C positive. The cumulative probabilities of total graft failure at 1, 3, and 5 years were 17.3%, 36.5%, and 55.4% versus 13.8%, 24.7%, and 40.5% among kidneys from donors where only one versus both kidneys were transplanted, respectively (log rank P=0.04).ConclusionsOur study shows a significantly higher discard rate for ECD/DCD kidneys versus prior reports. Some discarded ECD/DCD kidneys may be acceptable for transplantation. Additional studies are needed to evaluate the factors that influence decision making around the use of ECD/DCD kidneys.

Project description:ObjectivesTo 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.DesignProspective, population based cohort study.SettingFour French referral centres.ParticipantsConsecutive 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 measuresLong 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.ResultsThe 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.ConclusionsCirculating 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.

Dataset Information

Impact of targeted hypothermia in expanded-criteria organ donors on recipient kidney-graft function: study protocol for a multicentre randomised controlled trial (HYPOREME).

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Publications

Impact of targeted hypothermia in expanded-criteria organ donors on recipient kidney-graft function: study protocol for a multicentre randomised controlled trial (HYPOREME).

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