ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO641

Cellular and Molecular Landscape of AKI Post-Renal Transplant

Session Information

  • Transplantation: Basic
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 2001 Transplantation: Basic

Authors

  • McDaniels, Jennifer M., University of Maryland Baltimore, Baltimore, Maryland, United States
  • Shetty, Amol C., University of Maryland Baltimore, Baltimore, Maryland, United States
  • Rousselle, Thomas, University of Maryland Baltimore, Baltimore, Maryland, United States
  • Bardhi, Elissa, University of Maryland Baltimore, Baltimore, Maryland, United States
  • Maluf, Daniel G., University of Maryland Baltimore, Baltimore, Maryland, United States
  • Akalin, Enver, Albert Einstein College of Medicine, Bronx, New York, United States
  • Mas, Valeria R., University of Maryland Baltimore, Baltimore, Maryland, United States
Background

Acute kidney injury (AKI) is a risk factor for chronic kidney disease. Delayed graft function (DGF) post kidney transplantation (KT) is common due to ischemia/reperfusion injury and acute tubular necrosis (ATN). The pathophysiology of AKI post-KT and acute-to-chronic transition is unknown.

Methods

Kidney grafts with DGF <6 weeks post-KT (AKI graft with ATN (n=4); no evidence of acute/chronic Banff injury scores) and normal allografts (NA, n=4) (normal function/histology) were tested using single nuclei (sn)RNA-seq (10X Genomic Chromium Platform). Analysis was done with CellRanger. DEGs (FDR≤0.05) identified enriched GO terms and pathways.

Results

31,803 nuclei UMAP showed 19 main clusters (Fig 1A). AKI KT patients were divided as with (WGFr; n=2) and without graft function recovery (WoGFr; n=2). ATN WoGFr showed lower proximal tubule epithelial cells (PTEC) and increased fibroblasts (FB). Also, monocytes and T cells were increased in ATN WoGFr. FBs were higher (Fig 1B) and more transcriptionally active in AKI WoGFr compared to NA and AKI WGFr. A paired pre-implantation biopsy for an AKI WoGFr patient presented a temporal increase in FB with AKI onset (Fig 1C). PTECs showed high heterogeneity between NA and AKI grafts (Fig 1D). PTEC clusters 9-11 were mainly present in AKI grafts and enriched in myofibroblast markers (COL1A1,COL1A2, SLC26A3) (Fig 1E), marked metabolic dysfunction, and produced ECM. PTEC DEGs in AKI WoGFr were enriched in epithelial cell differentiation and tubule morphogenesis, suggesting a transitional cellular state.

Conclusion

Different immune and PTEC clusters were identified based on condition (NA vs ATN) and graft outcome (WGFr vs WoGFr), showing cell-type specific transcriptional profiles and pathways associated with impaired repair in AKI post-KT.

Funding

  • NIDDK Support