iScience (Oct 2023)
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
Affiliations
- Adam Wahida
- Medical Department III of Hematology and Oncology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Christoph Schmaderer
- Department of Nephrology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Maike Büttner-Herold
- Department of Nephropathology, Friedrich-Alexander University (FAU) Erlangen-Nurnberg, Erlangen, Germany
- Caterina Branca
- Medical Department III of Hematology and Oncology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Sainitin Donakonda
- Nephropathology Unit, Institute of Pathology, Hannover Medical School, Hannover, Germany
- Flora Haberfellner
- Department of Nephrology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Carlos Torrez
- Department of Nephrology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Jessica Schmitz
- Nephropathology Unit, Institute of Pathology, Hannover Medical School, Hannover, Germany
- Tobias Schulze
- Medical Department III of Hematology and Oncology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Tobias Seibt
- Transplant Center, University Hospital Munich, Ludwig-Maximilians-University (LMU), Munich, Germany
- Rupert Öllinger
- Institute of Molecular Oncology and Functional Genomics, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Thomas Engleitner
- Institute of Molecular Oncology and Functional Genomics, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Bernhard Haller
- Institute of AI and Informatics in Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
- Katja Steiger
- Institute of Pathology, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Roman Günthner
- Department of Nephrology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Georg Lorenz
- Department of Nephrology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Monica Yabal
- Nephropathology Unit, Institute of Pathology, Hannover Medical School, Hannover, Germany
- Quirin Bachmann
- Department of Nephrology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Matthias C. Braunisch
- Department of Nephrology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Philipp Moog
- Department of Nephrology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Edouard Matevossian
- Clinic of General, Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital Munich, Ludwig-Maximilians-University (LMU), Munich, Germany
- Volker Aßfalg
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
- Stefan Thorban
- Institute of Molecular Immunology and Experimental Oncology, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Lutz Renders
- Department of Nephrology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Martin R. Späth
- Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; CECAD, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
- Roman-Ulrich Müller
- Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; CECAD, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
- Dirk L. Stippel
- Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany
- Wilko Weichert
- Institute of Pathology, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Julia Slotta-Huspenina
- Institute of Pathology, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Sibylle von Vietinghoff
- Nephrology Section, Medical Clinic 1, University Hospital Bonn, Rheinische Friedrich Wilhelm University of Bonn, Bonn, Germany
- Ondrej Viklicky
- Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Douglas R. Green
- Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USA
- Roland Rad
- Nephropathology Unit, Institute of Pathology, Hannover Medical School, Hannover, Germany
- Kerstin Amann
- Department of Nephropathology, Friedrich-Alexander University (FAU) Erlangen-Nurnberg, Erlangen, Germany
- Andreas Linkermann
- Division of Nephrology, Clinic of Internal Medicine 3, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA
- Jan Hinrich Bräsen
- Nephropathology Unit, Institute of Pathology, Hannover Medical School, Hannover, Germany
- Uwe Heemann
- Department of Nephrology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany
- Stephan Kemmner
- Department of Nephrology, Klinikum rechts der Isar, TUM School of Medicine, Technical University of Munich, Munich, Germany; Transplant Center, University Hospital Munich, Ludwig-Maximilians-University (LMU), Munich, Germany; Corresponding author
- Journal volume & issue
-
Vol. 26,
no. 10
p. 107879
Abstract
Summary: 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.
