Kidney Week

Abstract: PO0336

Unraveling Single-Cell Responses in Human AKI

Session Information

• AKI: Mechanisms of Injury
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Hinze, Christian, Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin, Berlin, Germany

Christian Hinze, MD, DrMed

• Kocks, Christine, Berlin Institute for Medical Systems Biology, Max Delbrueck Center in the Helmholtz Association, Berlin, Germany

Christine Kocks,

• Leiz, Janna, Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin, Berlin, Germany

Janna Leiz,

• Karaiskos, Nikos, Berlin Institute for Medical Systems Biology, Max Delbrueck Center in the Helmholtz Association, Berlin, Germany

Nikos Karaiskos,

• Boltengagen, Anastasiya, Berlin Institute for Medical Systems Biology, Max Delbrueck Center in the Helmholtz Association, Berlin, Germany

Anastasiya Boltengagen,

• Skopnik, Christopher, Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin, Berlin, Germany

Christopher Skopnik,

• Klocke, Jan, Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin, Berlin, Germany

Jan Klocke,

• Hardenberg, Jan-Henderik Bernhard, Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin, Berlin, Germany

Jan-Henderik Bernhard Hardenberg,

• Stockmann, Helena, Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin, Berlin, Germany

Helena Stockmann,

• Gotthardt, Inka, Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin, Berlin, Germany

Inka Gotthardt,

• Obermayer, Benedikt, Berlin Institute of Health at Charité – Universitätsmedizin, Core Unit Bioinformatics, Berlin, Germany

Benedikt Obermayer,

• Haghverdi, Laleh, Berlin Institute for Medical Systems Biology, Max Delbrueck Center in the Helmholtz Association, Berlin, Germany

Laleh Haghverdi,

• Wyler, Emanuel, Berlin Institute for Medical Systems Biology, Max Delbrueck Center in the Helmholtz Association, Berlin, Germany

Emanuel Wyler,

• Landthaler, Markus, Berlin Institute for Medical Systems Biology, Max Delbrueck Center in the Helmholtz Association, Berlin, Germany

Markus Landthaler,

• Corman, Victor M., Institute of Virology, Charité-Universitätsmedizin, Berlin, Germany

Victor M. Corman,

• Busch, Jonas, Department of Urology, Charité-Universitätsmedizin, Berlin, Germany

Jonas Busch,

• Schneider, Wolfgang, Department of Pathology, Charité-Universitätsmedizin, Berlin, Germany

Wolfgang Schneider,

• Rudolph, Birgit, Department of Pathology, Charité-Universitätsmedizin, Berlin, Germany

Birgit Rudolph,

• Himmerkus, Nina, Institute of Physiology, Christian-Albrechts-Universität, Kiel, Germany

Nina Himmerkus,

• Bleich, Markus, Institute of Physiology, Christian-Albrechts-Universität, Kiel, Germany

Markus Bleich,

• Eckardt, Kai-Uwe, Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin, Berlin, Germany

Kai-Uwe Eckardt,

• Enghard, Philipp, Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin, Berlin, Germany

Philipp Enghard,

• Rajewsky, Nikolaus, Berlin Institute for Medical Systems Biology, Max Delbrueck Center in the Helmholtz Association, Berlin, Germany

Nikolaus Rajewsky,

• Schmidt-Ott, Kai M., Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin, Berlin, Germany

Kai M. Schmidt-Ott,

Background

Acute kidney injury (AKI) is frequently observed in critically ill patients and is associated with a poor prognosis. AKI has recently moved into the focus of interest during the SARS-CoV-2 pandemic as high rates of AKI have been reported in severe COVID-19. We aimed to delineate cell type-specific molecular phenotypes associated with human AKI, including COVID-associated AKI.

Methods

We analyzed human kidney tissues using histology and single-nuclei RNA sequencing. Samples included kidney biopsies obtained within 2 hours post mortem from patients who succumbed to critical illness with and without evidence of AKI. Samples also included tumor-adjacent normal kidney tissues obtained during surgeries. AKI cases included patients with severe courses of COVID-19 (COVID AKI) and patients with other types of critical illness associated with systemic inflammation (Non-COVID AKI). Post-mortem kidney tissues obtained 30 min, 1 hour and 2 hours after death from a brain-dead patient without AKI were analyzed to assess the impact of post-mortem effects.

Results

Single-nuclei sequencing from kidney tissues yielded data of high transcriptional depth, which allowed transcriptome-based identification and de-novo spatial reconstruction of kidney cells. Principal component and differential gene expression analyses indicated that the presence of clinically confirmed AKI was the primary driver of global kidney transcriptomes and that different molecular subtypes of AKI existed. In contrast, the sampling time post-mortem and the presence of COVID-19 had minor effects. Subclustering analyses of different kidney cell types identified subclasses of cells representing injured kidney tubular cells, which were marked by distinct biomarker expression and expression signatures signifying intrinsic responses to inflammation, an induction of epithelial-to-mesenchymal transition, and an upregulation of hitheto unrecognized novel receptor-ligand pairs.

Conclusion

We provide the first cell type-specific molecular atlas of human AKI, revealing unanticipated disease subtypes and cell type-specific injury patterns.