Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.
Matthew Mailing Centre for Translational Transplant Studies, London Health Sciences Centre, London, ON N6A 5A5, Canada.
Int J Mol Sci. 2024 Feb 12;25(4):2210. doi: 10.3390/ijms25042210.
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 ( < 0.05). Also, STS and Hemopure improved renal graft function compared with control grafts ( < 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.
肾移植是治疗终末期肾病的首选方法。目前,肾脏保存的金标准是在 4°C 下进行静态冷保存(SCS)。然而,SCS 会通过缺血再灌注损伤(IRI)导致肾移植物损伤。我们之前报道过在 4°C 下使用硫化氢供体硫代硫酸钠(STS)进行 SCS 后肾移植物的保护作用。因此,本研究旨在探讨在 10°C 下使用 STS 和血卟啉(血液替代品)进行 SCS 是否会提供类似的保护作用。我们在体外 IRI 模型中,将大鼠肾近端管状上皮细胞在 10°C 下进行缺氧-复氧 24 小时,并用或不用 STS 进行处理,并测量细胞活力。在体内,我们将 36 个 Lewis 大鼠供体肾脏在 10°C 下保存 24 小时,保存液中添加 STS、血卟啉或两者,然后进行移植。评估组织损伤和受体移植物功能参数,包括血清肌酐、血尿素氮、尿渗透压和肾小球滤过率(GFR)。与未处理的对照组细胞相比,在 10°C 下用 STS 处理的近端肾小管上皮细胞表现出更高的活力(<0.05)。此外,与对照组移植物相比,STS 和血卟啉在移植后早期改善了肾脏移植物的功能(<0.05),但长期功能未达到显著水平。总的来说,在 10°C 下使用 STS 和血卟啉补充进行肾移植保存具有增强移植物功能和减少肾脏损伤的潜力,提示一种减少 IRI 和移植后并发症的新方法。