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Abstract: FR-PO157

Urinary Single-Cell Sequencing Captures Intrarenal Injury and Repair Processes in Human AKI

Session Information

  • AKI: Mechanisms - II
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Klocke, Jan, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Kim, Seung Joon, Max-Delbruck-Centrum fur Molekulare Medizin in der Helmholtz-Gemeinschaft, Buch, Berlin, Germany
  • Skopnik, Christopher, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Hinze, Christian, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Wagner, Leonie Felicitas, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Prskalo, Luka, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Grothgar, Emil, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Goerlich, Nina, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Schmidt-Ott, Kai M., Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Eckardt, Kai-Uwe, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Rajewsky, Nikolaus, Max-Delbruck-Centrum fur Molekulare Medizin in der Helmholtz-Gemeinschaft, Buch, Berlin, Germany
  • Enghard, Philipp, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
Background

Acute kidney injury (AKI) is a major health issue, the outcome of which depends primarily on damage and reparative processes of tubular epithelial cells (TEC). Mechanisms underlying AKI remain incompletely understood, specific therapies are lacking and monitoring the course of AKI in clinical routine is confined to measuring urine output and plasma levels of filtration markers.

Methods

Here we demonstrate feasibility and potential of a novel approach to assess the cellular and molecular dynamics of AKI by establishing a robust urine-to-single cell RNA sequencing (scRNAseq) pipeline for excreted kidney cells via flow cytometry sorting. We analyzed 42,608 single cell transcriptomes of 40 urine samples from 32 AKI patients and compared our data with reference material from human AKI post-mortem biopsies and published mouse data.

Results

We demonstrate that urine-excreted TEC are mostly derived from distal nephron segments and are more abundant in patients with severe kidney injury. Their transcriptomes mirror intrarenal pathology and reflect distinct injury and repair processes, including oxidative stress, inflammation, and tissue rearrangement. We also describe a potentially AKI-specific abundant urinary excretion of adaptive progenitor-like cells.

Conclusion

In conclusion, single cell transcriptomics of kidney cells excreted in urine provides non-invasive, unprecedented insight into cellular processes underlying AKI, thereby opening novel opportunities for target identification, AKI sub-categorization and monitoring of natural disease course and interventions.

Graphical abstract