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 X

Kidney Week

Abstract: SA-OR66

Cell Subtypes and Cell-Specific Pathways Associated with Acute-to-Chronic Injury Transition in Posttransplant AKI

Session Information

Category: Transplantation

  • 2102 Transplantation: Clinical

Authors

  • Akalin, Enver, Montefiore Medical Center, New York, New York, United States
  • Azim, Shafquat, University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Shetty, Amol C., University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Rousselle, Thomas, University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Zubair, Haseeb, University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Mas, Valeria R., University of Maryland School of Medicine, Baltimore, Maryland, United States
Background

Kidney transplants (KT) offer a unique opportunity to evaluate molecular pathways involved in development and response to acute kidney injury (AKI). This study of transplanted kidneys with AKI aims to identify cells involved in injury or impaired reparation.

Methods

A total of 14 kidney samples (normal donor kidneys, n=5, normal allografts, n=4, and samples from patients with post-KT AKI, n=4 (<6weeks post-KT)) were evaluated using single nuclei (sn) RNA-seq.

Results

The analyses of 49,787 combined nuclei showed increased fibroblasts in post-KT AKI samples. Fibroblasts in post-KT AKI compared to normal allografts showed increased expression of genes enriched in extracellular matrix (ECM) organization, proteoglycans, ecollagen formation, and response to wounding. The analyses of these fibroblasts in 3 sex-mismatched cases using an XY-gene expression signature showed both donor- and recipient-derived fibroblasts (Fig 1A) not observed in normal allografts. Up-regulated genes in recipient fibroblasts were enriched in laminin interactions, ECM organization, and cellular response to TGF-β stimulus. Increased macrophages (MΦ) proportions in AKI samples, and 3 MΦ subsets were identified, including: MΦ1 (MRC1, LGMN, STAB1) and MΦ3 (FCN1, LYN1, KYNU1, RTN11), and the MΦ2 (CSF3R, LUCAT1, NCF1, LIMK2) (Fig 1B-C) characterized by markers of myofibroblasts/fibroblast-like (COL18A1, COL4A3, COL4A4, VCAN, AB3BP, FGL2, GAS6, THSD4). Resident and infiltrating MΦ present a pro-inflammatory profile and enriched in immunoregulatory response signaling pathways.

Conclusion

These novel data emphasize the critical role of resident MΦ in responding to injury transform into MΦ with fibroblast-like markers and a transcriptomic phenotype leading to impaired repair.

Funding

  • Other NIH Support