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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number107879
JournaliScience
Volume26
Issue number10
DOIs
StatePublished - 20 Oct 2023
Externally publishedYes

Keywords

  • Molecular biology
  • Nephrology

Fingerprint

Dive into the research topics of 'High RIPK3 expression is associated with a higher risk of early kidney transplant failure'. Together they form a unique fingerprint.

Cite this