High RIPK3 expression is associated with a higher risk of early kidney transplant failure

Adam Wahida; Christoph Schmaderer; Maike Büttner-Herold; Caterina Branca; Sainitin Donakonda; Flora Haberfellner; Carlos Torrez; Jessica Schmitz; Tobias Schulze; Tobias Seibt; Rupert Öllinger; Thomas Engleitner; Bernhard Haller; Katja Steiger; Roman Günthner; Georg Lorenz; Monica Yabal; Quirin Bachmann; Matthias C. Braunisch; Philipp Moog; Edouard Matevossian; Volker Aßfalg; Stefan Thorban; Lutz Renders; Martin R. Späth; Roman Ulrich Müller; Dirk L. Stippel; Wilko Weichert; Julia Slotta-Huspenina; Sibylle von Vietinghoff; Ondrej Viklicky; Douglas R. Green; Roland Rad; Kerstin Amann; Andreas Linkermann; Jan Hinrich Bräsen; Uwe Heemann; Stephan Kemmner

doi:10.1016/j.isci.2023.107879

High RIPK3 expression is associated with a higher risk of early kidney transplant failure

Adam Wahida, Christoph Schmaderer, Maike Büttner-Herold, Caterina Branca, Sainitin Donakonda, Flora Haberfellner, Carlos Torrez, Jessica Schmitz, Tobias Schulze, Tobias Seibt, Rupert Öllinger, Thomas Engleitner, Bernhard Haller, Katja Steiger, Roman Günthner, Georg Lorenz, Monica Yabal, Quirin Bachmann, Matthias C. Braunisch, Philipp MoogEdouard Matevossian, Volker Aßfalg, Stefan Thorban, Lutz Renders, Martin R. Späth, Roman Ulrich Müller, Dirk L. Stippel, Wilko Weichert, Julia Slotta-Huspenina, Sibylle von Vietinghoff, Ondrej Viklicky, Douglas R. Green, Roland Rad, Kerstin Amann, Andreas Linkermann, Jan Hinrich Bräsen, Uwe Heemann, Stephan Kemmner

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Abstract

Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation. The primary analysis included 374 baseline biopsy samples obtained from renal allografts 10 minutes after onset of reperfusion. RIPK3 was primarily detected in proximal tubular cells and distal tubular cells, both of which are affected by IRI. Time-to-event analysis revealed that high RIPK3 expression is associated with a significantly higher risk of one-year transplant failure and prognostic for one-year (death-censored) transplant failure independent of donor and recipient associated risk factors in multivariable analyses. The RIPK3 score also correlated with deceased donation, cold ischemia time and the extent of tubular injury.

Originalsprache	Englisch
Aufsatznummer	107879
Fachzeitschrift	iScience
Jahrgang	26
Ausgabenummer	10
DOIs	https://doi.org/10.1016/j.isci.2023.107879
Publikationsstatus	Veröffentlicht - 20 Okt. 2023

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Wahida, A., Schmaderer, C., Büttner-Herold, M., Branca, C., Donakonda, S., Haberfellner, F., Torrez, C., Schmitz, J., Schulze, T., Seibt, T., Öllinger, R., Engleitner, T., Haller, B., Steiger, K., Günthner, R., Lorenz, G., Yabal, M., Bachmann, Q., Braunisch, M. C., ... Kemmner, S. (2023). High RIPK3 expression is associated with a higher risk of early kidney transplant failure. iScience, 26(10), Artikel 107879. https://doi.org/10.1016/j.isci.2023.107879

@article{e6ef52eabbea4df5917859e147b4655e,

title = "High RIPK3 expression is associated with a higher risk of early kidney transplant failure",

abstract = "Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation. The primary analysis included 374 baseline biopsy samples obtained from renal allografts 10 minutes after onset of reperfusion. RIPK3 was primarily detected in proximal tubular cells and distal tubular cells, both of which are affected by IRI. Time-to-event analysis revealed that high RIPK3 expression is associated with a significantly higher risk of one-year transplant failure and prognostic for one-year (death-censored) transplant failure independent of donor and recipient associated risk factors in multivariable analyses. The RIPK3 score also correlated with deceased donation, cold ischemia time and the extent of tubular injury.",

keywords = "Molecular biology, Nephrology",

author = "Adam Wahida and Christoph Schmaderer and Maike B{\"u}ttner-Herold and Caterina Branca and Sainitin Donakonda and Flora Haberfellner and Carlos Torrez and Jessica Schmitz and Tobias Schulze and Tobias Seibt and Rupert {\"O}llinger and Thomas Engleitner and Bernhard Haller and Katja Steiger and Roman G{\"u}nthner and Georg Lorenz and Monica Yabal and Quirin Bachmann and Braunisch, {Matthias C.} and Philipp Moog and Edouard Matevossian and Volker A{\ss}falg and Stefan Thorban and Lutz Renders and Sp{\"a}th, {Martin R.} and M{\"u}ller, {Roman Ulrich} and Stippel, {Dirk L.} and Wilko Weichert and Julia Slotta-Huspenina and {von Vietinghoff}, Sibylle and Ondrej Viklicky and Green, {Douglas R.} and Roland Rad and Kerstin Amann and Andreas Linkermann and Br{\"a}sen, {Jan Hinrich} and Uwe Heemann and Stephan Kemmner",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = oct,

day = "20",

doi = "10.1016/j.isci.2023.107879",

language = "English",

volume = "26",

journal = "iScience",

issn = "2589-0042",

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Wahida, A, Schmaderer, C, Büttner-Herold, M, Branca, C, Donakonda, S, Haberfellner, F, Torrez, C, Schmitz, J, Schulze, T, Seibt, T, Öllinger, R, Engleitner, T, Haller, B, Steiger, K, Günthner, R, Lorenz, G, Yabal, M, Bachmann, Q, Braunisch, MC, Moog, P, Matevossian, E, Aßfalg, V , Thorban, S , Renders, L, Späth, MR, Müller, RU, Stippel, DL, Weichert, W, Slotta-Huspenina, J, von Vietinghoff, S, Viklicky, O, Green, DR, Rad, R, Amann, K, Linkermann, A, Bräsen, JH, Heemann, U & Kemmner, S 2023, 'High RIPK3 expression is associated with a higher risk of early kidney transplant failure', iScience, Jg. 26, Nr. 10, 107879. https://doi.org/10.1016/j.isci.2023.107879

TY - JOUR

T1 - High RIPK3 expression is associated with a higher risk of early kidney transplant failure

AU - Wahida, Adam

AU - Schmaderer, Christoph

AU - Büttner-Herold, Maike

AU - Branca, Caterina

AU - Donakonda, Sainitin

AU - Haberfellner, Flora

AU - Torrez, Carlos

AU - Schmitz, Jessica

AU - Schulze, Tobias

AU - Seibt, Tobias

AU - Öllinger, Rupert

AU - Engleitner, Thomas

AU - Haller, Bernhard

AU - Steiger, Katja

AU - Günthner, Roman

AU - Lorenz, Georg

AU - Yabal, Monica

AU - Bachmann, Quirin

AU - Braunisch, Matthias C.

AU - Moog, Philipp

AU - Matevossian, Edouard

AU - Aßfalg, Volker

AU - Thorban, Stefan

AU - Renders, Lutz

AU - Späth, Martin R.

AU - Müller, Roman Ulrich

AU - Stippel, Dirk L.

AU - Weichert, Wilko

AU - Slotta-Huspenina, Julia

AU - von Vietinghoff, Sibylle

AU - Viklicky, Ondrej

AU - Green, Douglas R.

AU - Rad, Roland

AU - Amann, Kerstin

AU - Linkermann, Andreas

AU - Bräsen, Jan Hinrich

AU - Heemann, Uwe

AU - Kemmner, Stephan

PY - 2023/10/20

Y1 - 2023/10/20

N2 - Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation. The primary analysis included 374 baseline biopsy samples obtained from renal allografts 10 minutes after onset of reperfusion. RIPK3 was primarily detected in proximal tubular cells and distal tubular cells, both of which are affected by IRI. Time-to-event analysis revealed that high RIPK3 expression is associated with a significantly higher risk of one-year transplant failure and prognostic for one-year (death-censored) transplant failure independent of donor and recipient associated risk factors in multivariable analyses. The RIPK3 score also correlated with deceased donation, cold ischemia time and the extent of tubular injury.

AB - Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation. The primary analysis included 374 baseline biopsy samples obtained from renal allografts 10 minutes after onset of reperfusion. RIPK3 was primarily detected in proximal tubular cells and distal tubular cells, both of which are affected by IRI. Time-to-event analysis revealed that high RIPK3 expression is associated with a significantly higher risk of one-year transplant failure and prognostic for one-year (death-censored) transplant failure independent of donor and recipient associated risk factors in multivariable analyses. The RIPK3 score also correlated with deceased donation, cold ischemia time and the extent of tubular injury.

KW - Molecular biology

KW - Nephrology

UR - http://www.scopus.com/inward/record.url?scp=85174810930&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2023.107879

DO - 10.1016/j.isci.2023.107879

M3 - Article

AN - SCOPUS:85174810930

SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 10

M1 - 107879

ER -

High RIPK3 expression is associated with a higher risk of early kidney transplant failure

Abstract

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