Evaluating the Effects of Kidney Preservation at 10 °C with Hemopure and Sodium Thiosulfate in a Rat Model of Syngeneic Orthotopic Kidney Transplantation

Author:

Abou Taka Maria12ORCID,Dugbartey George J.2345ORCID,Richard-Mohamed Mahms23ORCID,McLeod Patrick2,Jiang Jifu2,Major Sally2,Arp Jacqueline2,O’Neil Caroline6,Liu Winnie7,Gabril Manal7,Moussa Madeleine7,Luke Patrick2357,Sener Alp1235

Affiliation:

1. Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada

2. Matthew Mailing Centre for Translational Transplant Studies, London Health Sciences Centre, London, ON N6A 5A5, Canada

3. Multi-Organ Transplant Program, London Health Sciences Centre, London, ON N6A 5A5, Canada

4. Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra P.O. Box LG 1181, Ghana

5. London Health Sciences Centre, Department of Surgery, Division of Urology, London, ON N6A 5A5, Canada

6. The Molecular Pathology Core, Robarts Research Institute, London, ON N6A 5A5, Canada

7. London Health Sciences Centre, Department of Pathology and Laboratory Medicine, London, ON N6A 5A5, Canada

Abstract

Kidney transplantation is preferred for end-stage renal disease. The current gold standard for kidney preservation is static cold storage (SCS) at 4 °C. However, SCS contributes to renal graft damage through ischemia–reperfusion injury (IRI). We previously reported renal graft protection after SCS with a hydrogen sulfide donor, sodium thiosulfate (STS), at 4 °C. Therefore, this study aims to investigate whether SCS at 10 °C with STS and Hemopure (blood substitute), will provide similar protection. Using in vitro model of IRI, we subjected rat renal proximal tubular epithelial cells to hypoxia–reoxygenation for 24 h at 10 °C with or without STS and measured cell viability. In vivo, we preserved 36 donor kidneys of Lewis rats for 24 h in a preservation solution at 10 °C supplemented with STS, Hemopure, or both followed by transplantation. Tissue damage and recipient graft function parameters, including serum creatinine, blood urea nitrogen, urine osmolality, and glomerular filtration rate (GFR), were evaluated. STS-treated proximal tubular epithelial cells exhibited enhanced viability at 10 °C compared with untreated control cells (p < 0.05). Also, STS and Hemopure improved renal graft function compared with control grafts (p < 0.05) in the early time period after the transplant, but long-term function did not reach significance. Overall, renal graft preservation at 10 °C with STS and Hemopure supplementation has the potential to enhance graft function and reduce kidney damage, suggesting a novel approach to reducing IRI and post-transplant complications.

Funder

Department of Surgery Internal Research Fund, Western University

Publisher

MDPI AG

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