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Characterization of Chronic Renal Allograft Dysfunction at Single Cell Resolution

C. Kuscu1, C. Kuscu2, A. Shetty3, M. Talwar4, J. Eason2, D. G. Maluf5, V. Mas6

1Surgery, James D Eason Transplant Institute, UTHSC, Memphis, TN, 2Surgery, James D Eason Transplant Institute, Memphis, TN, 3Institute for Genome Sciences, School of Medicine, University of Maryland, Baltimore, MD, 4Nephrology, James D Eason Transplant Institute, Memphis, TN, 5Surgery, Program in Transplantation - University of Maryland, Baltimore, MD, 6Surgery, Division of Surgical Science - University of Maryland, Baltimore, MD

Meeting: 2021 American Transplant Congress

Abstract number: 1065

Keywords: Graft function, Kidney, Kidney transplantation, Outcome

Topic: Clinical Science » Kidney » Kidney Complications: Immune Mediated Late Graft Failure

Session Information

Session Name: Kidney Complications: Immune Mediated Late Graft Failure

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: Chronic allograft dysfunction (CAD) is one of the major complications after kidney transplantation. Hereby, we aim to assess the molecular and cellular mechanism of Chronic Allograft Dysfunction at a single cell resolution to identify potential interventions. Single-cell genomics has played unprecedented role for diagnosis and finding novel treatment methods.

*Methods: We performed single nuclei sequencing from 8 kidney allograft biopsies (3 normal allografts (normal histology and normal creatinine at 24 months post-transplant), 2 Chronic Allograft Dysfunction (CAD) with inflammation, and 3 CAD without inflammation) using droplet based 10X Genomics Chromium platform. Data is analyzed on “Cell-Ranger” pipeline and “Seurat” package was used for cell clustering and cell identification. CAD classifications were done using Banff criteria.

*Results: We obtained >40,000 cells in our analysis with an average of 1400 genes per cell (Fig 1a). We identified 17 different clusters in aggregated analysis. Our single-nuclei RNA-seq allow us to identify rare pericytes and kidney progenitor cells in addition to the main cell types of kidney such as tubular cells and endothelial cells (Fig 1 A-B). Interestingly, we identified significant number podocytes which cannot be detected by ordinary single-cell RNA sequencing. ARL17B and FKBP5 genes are found to be differentially expressed in several cell types including tubular cells, podocytes when CAD(- inflammation) compared to CAD(+ inflammation).

*Conclusions: Our results identified pericytes and kidney progenitor cells (in addition to the main cell types of kidney such as tubular cells and endothelial cells) in patients with chronic allograft dysfunction

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To cite this abstract in AMA style:

Kuscu C, Kuscu C, Shetty A, Talwar M, Eason J, Maluf DG, Mas V. Characterization of Chronic Renal Allograft Dysfunction at Single Cell Resolution [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/characterization-of-chronic-renal-allograft-dysfunction-at-single-cell-resolution/. Accessed May 16, 2025.

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