Kidney Week

Abstract: SA-PO0173

Analysis of the RNA-Binding Protein Landscape in Porcine Kidneys Following Ischemia-Reperfusion Injury

Session Information

• AKI: Mechanisms - 3
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Mueller, Roman-Ulrich, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany

Roman-Ulrich Mueller, MD

• Hinrichs, Steffen, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany

Steffen Hinrichs

• Bohl, Katrin, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany

Katrin Bohl, PhD

• Lopes, Francisco José Calheiros Craveiro, Exzellenzcluster CECAD in der Universitat zu Koln, Cologne, NRW, Germany

Francisco José Calheiros Craveiro Lopes, MSc

• Goebel, Heike, Institute of Pathology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany

Heike Goebel, MD

• Mueller, Stefan, Exzellenzcluster CECAD in der Universitat zu Koln, Cologne, NRW, Germany

Stefan Mueller, PhD

• Pollmann, Berit, Department of Anesthesiology and Intensive Care Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany

Berit Pollmann, DrMed

• Benzing, Thomas, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany

Thomas Benzing, MD, PhD, FASN

• Boor, Peter, Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Aachen, Germany

Peter Boor, MD, PhD

• Schermer, Bernhard, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany

Bernhard Schermer, MD

• Ignarski, Michael, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany

Michael Ignarski, PhD

Background

Acute kidney injury (AKI) is a common complication in hospitalized patients and is associated with increased mortality. Despite this, no targeted therapy is available to date. RNA-binding proteins (RBPs) are key regulators of cellular biology and have been implicated in AKI. However, a comprehensive analysis of their role in AKI is lacking. In this study, we used porcine kidneys to investigate how RBPs are affected by ischemia-reperfusion injury (IRI) following cardiopulmonary resuscitation. By using pigs as a model organism, we were able to benefit from a kidney damage pattern that is more similar to humans than to rodents. Using enhanced RNA interactome capture (eRIC), we identified and quantified these RBPs by mass spectrometry. Additionally, we used kidney proteome and transcriptome measurements to complement the analysis. To examine the tissue specific evolutionary conservation of renal RBPs, we isolated and measured RBPs from human kidneys.

Methods

Ischemia reperfusion injured porcine kidneys were obtained from a large-scale pig resuscitation study. In addition, healthy human kidney was harvested from three tumor nephrectomy patients. RBPs were isolated from these kidneys by eRIC and measured by LC-MS/MS. The RNA interactome data was complemented with whole proteome and transcriptome analysis.

Results

We identified 818 RBPs in porcine and 561 RBPs in human kidney with 403 RBPs shared between both. 5% of the identified RBPs have not been described previously. Following IRI, 27 RBPs showed differential RNA binding, with 6 of the 27 being metabolic enzymes. Furthermore, 19 of the 27 were found in our human renal RNA interactome and/or the mice renal RNA interactome from Perez-Perri et al. (2022).

Conclusion

With our combined eRIC and proteome approach we have identified differentially bound RBPs following IRI in porcine kidneys. Among these, RBPs that have been previously associated with AKI and/or function as metabolic enzymes. The tissue specific conservation of these RBPs in humans highlights the translational potential of these findings. A deeper understanding of the role these RNA-protein interactions play in AKI will potentially lead to the identification of novel therapeutic targets for AKI in human.

Funding

• Government Support – Non-U.S.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025v4xdbtgm