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

Int J Mol Sci. 2024 Feb 12;25(4):2210. doi: 10.3390/ijms25042210.

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.

Keywords: Hemopure; graft and recipient survival; ischemia–reperfusion injury (IRI); kidney transplantation; sodium thiosulfate (STS); static cold storage (SCS).

MeSH terms

  • Animals
  • Graft Survival
  • Hemoglobins*
  • Kidney
  • Kidney Transplantation*
  • Organ Preservation
  • Rats
  • Rats, Inbred Lew
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / prevention & control
  • Thiosulfates*

Substances

  • HBOC 201
  • sodium thiosulfate
  • Hemoglobins
  • Thiosulfates

Grants and funding

This work was supported by the Department of Surgery Internal Research Fund, Western University.