Defects in Kim-1 Do Not Result In Delayed Graft Function After Kidney Transplantation

R. S. Suri¹, J. Lee², M. Ban³, B. Shrum², O. Z. Ismail⁴, S. Leckie⁵, A. McIntyre³, Q. Xu⁶, S. H. Lee², S. de Chickera², R. A. Hegele², L. Gunaratnam²

¹Research Institute of the McGill University Health Center, Montreal, QC, Canada, ²Schulich School of Medicine and Dentistry, Western University, Lodnon, ON, Canada, ³Robarts Research Institute, Lodnon, ON, Canada, ⁴University of Alberta, Edmonton, AB, Canada, ⁵London Health Sciences Centre, Lodnon, ON, Canada, ⁶University of Pittsburg Medical Center, Pittsburg, PA

Meeting: 2022 American Transplant Congress

Abstract number: 672

Keywords: Epithelial cells, Genomics, Graft function, Kidney transplantation

Topic: Basic Science » Basic Science » 14 - Ischemia Reperfusion

Session Information

Session Name: Ischemia Reperfusion

Session Type: Poster Abstract

Date: Saturday, June 4, 2022

Session Time: 5:30pm-7:00pm

Presentation Time: 5:30pm-7:00pm

Location: Hynes Halls C & D

*Purpose: Tissue repair is critical to restore organ function after ischemia-reperfusion injury (IRI) during transplantation. During renal injury, upregulation of kidney injury molecule-1 (KIM-1) transforms kidney epithelial cells into phagocytes which, via KIM-1 mucin domain, bind to and engulf apoptotic and necrotic cells. In murine models, KIM-1-mediated phagocytosis reduces renal dysfunction and promotes repair after native kidney and transplant-related IRI, but this has not been studied in humans.

*Methods: We expressed three common mucin domain nonsynonymous variants (rs12522248, rs45439103, rs6149307) of the human KIM-1 gene (HAVCR1) in human kidney cells and tested phagocytic capacity of the resulting proteins. To determine if impaired KIM-1-mediated phagocytosis predisposes to acute kidney injury after IRI in humans, we genotyped 627 consecutive kidney donors and assessed risk of delayed graft function (DGF) in recipients.

*Results: Cells expressing these variants exhibited markedly reduced phagocytosis of apoptotic and necrotic cells, with rs6149307 being the most severe (<5% phagocytosis). Risk of DGF in recipients of donor kidneys homozygous for rs6149307 was not significantly increased compared to recipients of donor kidneys with one or no copies (adjusted relative risk 1.0 [0.7-1.3]).

*Conclusions: Contrary to prevailing theory, our results suggest KIM-1-mediated phagocytosis is not essential for tissue repair after renal IRI in humans.

To cite this abstract in AMA style:

Suri RS, Lee J, Ban M, Shrum B, Ismail OZ, Leckie S, McIntyre A, Xu Q, Lee SH, Chickera Sde, Hegele RA, Gunaratnam L. Defects in Kim-1 Do Not Result In Delayed Graft Function After Kidney Transplantation [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/defects-in-kim-1-do-not-result-in-delayed-graft-function-after-kidney-transplantation/. Accessed May 30, 2025.

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