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Kidney Week

Abstract: SA-OR19

Immune Cells as Drivers of Kidney Myofibroblast Formation and Fibrosis After Acute Cardiac Dysfunction

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Burfeind, Kevin G., Oregon Health & Science University, Portland, Oregon, United States
  • Funahashi, Yoshio, Portland VA Medical Center, Portland, Oregon, United States
  • Munhall, Adam C., Oregon Health & Science University, Portland, Oregon, United States
  • Eiwaz, Mahaba B., Oregon Health & Science University, Portland, Oregon, United States
  • Hutchens, Michael, Portland VA Medical Center, Portland, Oregon, United States
Background

Acute kidney injury (AKI) is a cause of chronic kidney disease (CKD). The AKI to CKD transition presents an opportunity for early intervention to prevent CKD. Myofibroblast formation is a hallmark of CKD. We have performed extensive mechanistic investigation in a translational model of AKI-CKD transition, cardiac arrest and cardiopulmonary resuscitation (CA/CPR), in which all animals develop CKD at 7 weeks. The purpose of this study was to identify potential immune drivers of myofibroblast formation.

Methods

Cardiac arrest was induced with potassium chloride in anesthestized intubated mice. Resuscitation was performed with epinephrine and chest compressions. Flow cytometry was used to profile the immune and mesenchymal landscapes during the AKI to CKD transition after CA/CPR (Fig. 1A). Kidney single nuclear RNA sequencing (snRNASeq) was performed at 1 day after CA/CPR, and CellChat was used to interrogate interactions between immune cells and myofibroblast precursors.

Results

Monocytes and natural killer cells increased in the kidney after CA/CPR (Fig. 1B). PDGFRB+ cells increased at 7 days (Fig. 1C), and immune cells colocalized with aSMA+ myofibroblasts after CA/CPR (Fig. 1D). snRNASeq revealed several distinct populations of kidney cells (Fig. 1E). High resolution subclustering combined with CellChat identified significantly upregulated interaction networks between immune cells and mesenchymal cells, including CD226 and CD96 signaling (Fig. 1E and F).

Conclusion

CA/CPR induces acute and lasting renal inflammation, which correlates with myofibroblast expansion. Lymphocytes communicate with myofibroblast precursors, revealing potential therapeutic targets.

Funding

  • Veterans Affairs Support