Thesis Format
Monograph
Degree
Master of Science
Program
Microbiology and Immunology
Supervisor
Sener, Alp
Abstract
Kidney transplantation is the best treatment for end-stage renal disease but is challenged by ischemia-reperfusion injury (IRI). We recently showed that adding sodium thiosulfate (STS), a hydrogen sulfide (H2S) donor, during organ storage protects against IRI. However, pre-treating the transplant donor with STS may further suppress IRI by establishing a protective environment in the kidney before ischemia. We hypothesized that STS pre-treatment would protect renal grafts against transplantation-induced IRI by suppressing oxidative stress, cell death, and inflammation, thereby improving graft function. STS pre-treatment reduced cell death in an in vitro model of hypoxia-reoxygenation injury. In a rat model of kidney transplantation, STS pre-treatment reduced graft apoptosis, acute tubular necrosis, and neutrophil inflammation, which may be due to reduced oxidative stress. Our results suggest that STS pre-treatment may protect against IRI induced by kidney transplantation, warranting future study.
Summary for Lay Audience
Kidney transplantation is the best treatment for patients with kidney failure. However, during transplantation, the kidney is damaged due to the process of stopping and restoring blood supply and oxygen to the kidney. This damage is known as ischemia-reperfusion injury (IRI). The main causes of IRI are cell death, inflammation, and toxic molecules called reactive oxygen species (ROS). These events damage the transplanted kidney and reduce its function. We recently found that sodium thiosulfate (STS), a clinically approved drug that releases hydrogen sulfide (H2S) in the body, can protect against IRI when it is added to the solution in which the kidney is stored before transplantation. However, treating the kidney donor with STS before the kidney is removed could prepare the kidney to better resist the damage that occurs from IRI during transplantation. As a result, we predicted that treating kidney donors with STS would reduce damage to the kidney caused by IRI by decreasing ROS levels, cell death, and inflammation, leading to better kidney function after transplantation. We found that treating kidney cells with STS before reducing and then restoring their oxygen supply, which mimics IRI, reduced cell death. In a rat model of kidney transplantation, treating the kidney donors with STS reduced cell death and inflammation in the transplanted kidneys, which may be due to reduced ROS levels. Our results suggest that treating kidney donors with STS can protect transplanted kidneys against damage caused by IRI. This approach could be a feasible and affordable way to improve outcomes for kidney transplant recipients. Our study provides evidence for future research on STS pre-treatment.
Recommended Citation
Nelson, Pierce BR, "Effect of sodium thiosulfate pre-treatment on renal ischemia-reperfusion injury" (2024). Electronic Thesis and Dissertation Repository. 10121.
https://ir.lib.uwo.ca/etd/10121