Improving the outcome of kidney transplantation by ameliorating renal ischemia reperfusion injury: lost in translation?

Abstract

Kidney transplantation is the treatment of choice in patients with end stage renal disease. During kidney transplantation ischemia reperfusion injury (IRI) occurs, which is a risk factor for acute kidney injury, delayed graft function and acute and chronic rejection. Kidneys from living donors show a superior short- and long-term graft survival compared with deceased donors. However, the shortage of donor kidneys has resulted in expansion of the donor pool by using not only living- and brain death donors but also kidneys from donation after circulatory death and from extended criteria donors. These grafts are associated with an increased sensitivity to IRI and decreased graft outcome due to prolonged ischemia and donor comorbidity. Therefore, preventing or ameliorating IRI may improve graft survival. Animal experiments focus on understanding the mechanism behind IRI and try to find methods to minimize IRI either before, during or after ischemia. This review evaluates the different experimental strategies that have been investigated to prevent or ameliorate renal IRI. In addition, we review the current state of translation to the clinical setting. Experimental research has contributed to the development of strategies to prevent or ameliorate IRI, but promising results in animal studies have not yet been successfully translated to clinical use.

miR-191 secreted by platelet-derived microvesicles induced apoptosis of renal tubular epithelial cells and participated in renal ischemia-reperfusion injury via inhibiting CBS

“…Renal transplantation is a good treatment for patients with end stage renal disease, and renal IR injury is a common cause for delayed function of renal transplantation which is a relevant factor in determining high morbidity and mortality in renal allograft rejection [12,13]. Strategies to reduce renal IR injury can be focused on metabolic and anti-inflammatory strategies, antioxidant therapy, inhibition of innate inflammatory response, and anti-apoptosis treatment [14].…”

Transplantation and Damage-Associated Molecular Patterns (DAMPs)

“…Certainly, these severe systemic innate immune processes occurring under BD conditions can causatively be made responsible, besides IRI, for the well‐known phenomenon of delayed graft function of kidneys removed from BD donors .…”

Evaluation of Vitamin C Supplementation on Kidney Function and Vascular Reactivity Following Renal Ischemic Injury in Mice

“…Ischemia/reperfusion injury (IRI) is an unavoidable consequence of organ transplantation procedure [3]. The inflammatory response involved in IRI could expose the organ to immune responses and cause delayed graft function and allograft rejection [4]. There is convincing evidence revealing the role of oxidative stress which activates different signaling pathways in renal ischemic injury [5,6].…”