Impact of Expanded Criteria Variables on Outcomes of Kidney Transplantation from Donors After Cardiac Death

Nagaraja, Pramod; Roberts, Gareth W.; Stephens, Michael; Horvath, Szabolcs; Káposztás, Zsolt; Chávez, Rafael; Asderakis, Argiris

doi:10.1097/tp.0000000000000304

Cited by 44 publications

(31 citation statements)

References 12 publications

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“…The extent to which donor and recipient‐related characteristics influence the magnitude of IRI and/or DGF occurrence, beyond accepted clinical risk factors for DGF, remains to be proven (Menke et al, 2014; Mundt et al, 2015; Schroppel & Legendre, 2014), particularly in the context of allograft repair, or regeneration pathways, activated in response to IRI. Increased demand for organ donation, coupled with increasing chronological age and associated comorbidities in the donor population, has necessitated the use of organs that have been previously deemed as marginal for clinical use (Morrissey & Monaco, 2014; Nagaraja et al, 2015). …”

Section: Introductionmentioning

confidence: 99%

A molecular signature for delayed graft function

et al. 2018

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Chronic kidney disease and associated comorbidities (diabetes, cardiovascular diseases) manifest with an accelerated ageing phenotype, leading ultimately to organ failure and renal replacement therapy. This process can be modulated by epigenetic and environmental factors which promote loss of physiological function and resilience to stress earlier, linking biological age with adverse outcomes post‐transplantation including delayed graft function (DGF). The molecular features underpinning this have yet to be fully elucidated. We have determined a molecular signature for loss of resilience and impaired physiological function, via a synchronous genome, transcriptome and proteome snapshot, using human renal allografts as a source of healthy tissue as an in vivo model of ageing in humans. This comprises 42 specific transcripts, related through IFNγ signalling, which in allografts displaying clinically impaired physiological function (DGF) exhibited a greater magnitude of change in transcriptional amplitude and elevated expression of noncoding RNAs and pseudogenes, consistent with increased allostatic load. This was accompanied by increased DNA methylation within the promoter and intragenic regions of the DGF panel in preperfusion allografts with immediate graft function. Pathway analysis indicated that an inability to sufficiently resolve inflammatory responses was enabled by decreased resilience to stress and resulted in impaired physiological function in biologically older allografts. Cross‐comparison with publically available data sets for renal pathologies identified significant transcriptional commonality for over 20 DGF transcripts. Our data are clinically relevant and important, as they provide a clear molecular signature for the burden of “wear and tear” within the kidney and thus age‐related physiological capability and resilience.

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Section: Introductionmentioning

confidence: 99%

A molecular signature for delayed graft function

et al. 2018

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“…Inkstų transplantacijų rezultatus tyrusių studijų rezultatai patvirtina, kad donorystės tipas nepakeičia pacientų po transplantacijos baigčių (21)(22)(23)(24). Pacientams, kuriems buvo persodinti inkstai, paimti iš DNNK donoro, buvo didesnis procentas vėluojančios inkstų funkcijos ankstyvuoju potransplantaciniu periodu, tačiau vėlyvajame periode kreatinino kiekis ir recipientų išgyvenamumas statistiškai reikšmingai nesiskyrė, lyginant su transplantuotais organais iš donorų po smegenų mirties (13,25).…”

Section: įVadasunclassified

Naujo Donorystės Modelio Reikšmė Potencialių Mirusių Donorų Skaičiui Kauno Donoriniame Centre

et al. 2017

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Raktažodžiai: organų donoras, donorystė dėl negrįžta-mai nutrūkusios kraujotakos, potencialus donoras, mirčių analizė, donorinis centras. SantraukaOrganų transplantacija yra efektyviausias ir ekonomiškai naudingiausias, o kai kuriais atvejais ir vienintelis gydymo būdas esant terminaliniam vidaus organų funkcijos nepakankamumui. Pagrindinė kliūtis transplantacijai -donorinių organų trūkumas. Pasaulinėje praktikoje geriausi rezultatai pasiekiami, kai kartu taikomi skirtingi donorystės modeliai: gyvoji donorytė, donorystė po smegenų mirties ir donorystė dėl negrįžtamai nutrūkusios kraujotakos (DNNK). Nuo 2016 m. sausio 1d., pakeitus įstatyminę bazę, Lietuvoje atsirado galimybė ruošti DNNK, tačiau kokia galima šio modelio įtaka organų donorų skaičiui šalyje nėra žinoma. Siekiant pamatuoto ir tvaraus DNNK programos diegimo LSMUL KK atlikta visų suaugusių pacientų mirčių, 2015 m. registruotų Kauno klinikose ir Valstybinės teismo medicinos tarnybos (VTMT) Kauno skyriaus registre, analizė ir identifikuoti potencialūs DNNK. Analizės metu naudoti visuotinai priimti potencialaus DNNK demografiniai, ligos anamnezės ir su mirties procesu susiję laiko kriterijai. Dėl Lietuvoje galiojančių įsta-tymų įtraukti tik nekontroliuojami DNNK. Nustatyta, kad iš 2356 mirusiųjų potencialaus DNNK kriterijus atitiko 56 mirusieji, taip padidindami potencialių organų donorų skaičių LSMUL KK donoriniame centre 119,5 %. Remiantis atlikta analize galima teigti, kad sėkmingai įdiegus nekontroliuojamos DNNK modelį Kauno klinikų donoriniame centre galima tikėtis žen-klaus donorinių organų padidėjimo. DNNK -donoras dėl negrįžtamai nutrūkusios kraujotakos, ŽIV -žmogaus imunodeficito virusas, CD -cukrinis diabetas, IFN -inkstų funkcijos nepakankamumas, CNS -centrinė nervų sistema. PD -potencialūs donorai, SM -smegenų mirtis, DNNK -donorai dėl negrįžtamai nutrūkusios kraujotakos. DNNK -donorai dėl negrįžtamai nutrūkusios kraujotakos, SPS -skubios pagalbos skyrius, ITS -intensyviosios terapijos skyrius. ĮvadasOrganų transplantacija pagerina gyvenimo kokybę, pailgina gyvenimo trukmę ir yra ekonomiškai naudingiausias gydymo būdas pacientams, sergantiems paskutinės stadijos inkstų nepakankamumu (1-4). Esant kepenų ar plaučių terminaliniam nepakankamumui tai gali būti vienintelis gydymo būdas (5-7). Pagrindinė kliūtis organų transplantacijai -donorinių organų trūkumas (2, 4). Pasaulinė sveikatos organizacija (PSO) skatina maksimaliai išnaudoti kiekvienos šalies organų donorystės galimybes siekiant užtikrinti donorinių organų poreikio patenkinimą. Tai atlikti optimizuojant vidinius resursus ir ypatingas pastangas skiriant negyvosios donorystės skatinimui, nes tokiu būdu kovojama su organų prekyba iš trečiųjų šalių (8, 9). Lietuvoje, kaip ir kitose išsivysčiusiose Vakarų šalyse, stebimos organų donorų po smegenų mirties mažėjimo tendencijos, sąlygotos mažėjančio eismo įvykių skaičiaus su letaliomis baigtimis, gerėjančių neurokritinių ligonių gydymo rezultatų (10-12). Organų trū-kumo problemai spręsti įvairios šalys naudoja skirtingas strategijas ir donoryst...

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“…2,[6][7][8][9][10][11] This strategy would permit organ recovery prior to withdrawal of life sustaining treatments and provide an opportunity for patients with severe neurologic injury to donate. 4,[13][14][15] Despite benefits, recovery of organs before circulatory death raises ethical concerns for stakeholders particularly related to the boundaries between life and death and how donation is causally associated with donor death. 4,[13][14][15] Despite benefits, recovery of organs before circulatory death raises ethical concerns for stakeholders particularly related to the boundaries between life and death and how donation is causally associated with donor death.…”

Section: Introductionmentioning

confidence: 99%

“…Given estimates that 27% of patients fail to donate after circulatory death (DCD), 12 this proposal has potential to reduce the harms of nondonation, increase organs for transplant, and reduce ischemic damage suffered during withdrawal of mechanical support. 4,[13][14][15] Despite benefits, recovery of organs before circulatory death raises ethical concerns for stakeholders particularly related to the boundaries between life and death and how donation is causally associated with donor death. Although a 2017 Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) Ethics Committee white paper expressed support for exploring living donation in patients with fatal diseases, 15 data about stakeholder interests are limited.…”

Section: Introductionmentioning

confidence: 99%

Family and transplant professionals’ views of organ recovery before circulatory death for imminently dying patients: A qualitative study using semistructured interviews and focus groups

Zimmermann

Baggett

Taylor

et al. 2019

American Journal of Transplantation

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Abbreviations: DBD, donation after brain death; DCD, donation after circulatory death;OPO, organ procurement organization; UNOS, United Network for Organ Sharing.Donation before circulatory death for imminently dying patients has been proposed to address organ scarcity and harms of nondonation. To characterize stakeholder attitudes about organ recovery before circulatory death we conducted semistructured interviews with family members (N = 15) who had experienced a loved one's unsuccessful donation after circulatory death and focus groups with professional stakeholders (surgeons, anesthesiologists, critical care specialists, palliative care specialists, organ procurement personnel, and policymakers, N = 46). We then used qualitative content analysis to characterize these perspectives. Professional stakeholders believed that donation of all organs before circulatory death was unacceptable, morally repulsive, and equivalent to murder; consent for such a procedure would be impermissible. Respondents feared the social costs related to recovery before death were too high. Although beliefs about recovery of all organs were widely shared, some professional stakeholders could accommodate removal of a single kidney before circulatory death. In contrast, family members were typically accepting of donation before circulatory death for a single kidney, and many believed recovery of all organs was permissible because they believed the cause of death was the donor's injury, not organ procurement. These findings suggest that definitions of death and precise rules around organ donation are critical for professional stakeholders, whereas donor families find less relevance in these constructs for determining the acceptability of organ donation. Donation of a single kidney before circulatory death warrants future exploration. K E Y W O R D Sclinical research/practice, donors and donation, ethics, ethics and public policy, organ procurement, organ procurement and allocation, organ transplantation in general, qualitative research | 2233 ZIMMERMANN Et Al.

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Impact of Expanded Criteria Variables on Outcomes of Kidney Transplantation from Donors After Cardiac Death

Abstract: Short-term graft survival in DCD-ECD transplants was comparable to DCD-SCD and DBD-ECD transplants albeit with poorer allograft function at 2 years. Quality-of-life studies are needed to determine the true value of these transplants, particularly when performed to older recipients.

Cited by 44 publications

References 12 publications

A molecular signature for delayed graft function

A molecular signature for delayed graft function

Naujo Donorystės Modelio Reikšmė Potencialių Mirusių Donorų Skaičiui Kauno Donoriniame Centre

Family and transplant professionals’ views of organ recovery before circulatory death for imminently dying patients: A qualitative study using semistructured interviews and focus groups

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