# Preclinical Models of Donation-After-Circulatory-Death and Brain-Death: Advances in Kidney Preservation and Transplantation

## TL;DR

This paper reviews strategies to improve kidney preservation from deceased donors to enhance transplant outcomes and address the donor shortage.

## Contribution

The paper provides a comprehensive review of preclinical models and emerging preservation techniques for deceased donor kidneys.

## Key findings

- Ischemia–reperfusion injury significantly impacts deceased donor kidney function.
- Alternative preservation methods like machine perfusion show promise in improving graft viability.
- Supplemental compounds and oxygen carriers during storage may reduce post-transplant complications.

## Abstract

Kidney transplantation is the optimal treatment for patients with kidney failure. Unfortunately, the demand for donor kidneys outweighs the number of donor kidneys available. This has created a global donor kidney shortage crisis and a long waiting list of transplant recipients, and thus, has necessitated the use of kidneys from deceased donors. However, compared to living donor kidneys, kidneys from deceased donors are more vulnerable to injury due to the lack of blood supply upon death, and injury from the transplantation procedure involving cold preservation and restoration of blood supply upon transplantation. In recent years, alternative preservation methods, including addition of protective agents to storage solutions, have emerged, with the goal of improving the quality and function of kidneys from deceased donors, reducing post-transplant complications, and eventually reducing the number of patients on the transplant waiting list. In this review, we discussed the mechanisms of injury in deceased donor kidneys. In addition, we also discussed within the limits of present literature the preservation strategies tested in animal models. Finally, the review ends with a discussion on emerging therapeutic interventions aimed at improving adverse post-transplant outcomes.

Chronic kidney disease (CKD) affects over 10% of the global population, with end-stage renal disease (ESRD) necessitating renal replacement therapy. Kidney transplantation remains the optimal treatment for ESRD. However, the global donor kidney shortage crisis has led to increased reliance on deceased donor kidneys. Donors are classified as either donation after brain death (DBD) or donation after circulatory death (DCD), each associated with distinct ischemic injuries that impact graft function. Ischemia–reperfusion injury (IRI) plays a pivotal role in transplant outcomes, triggering oxidative stress, inflammation, and endothelial dysfunction. While static cold storage (SCS) remains the gold standard for organ preservation, alternative strategies such as hypothermic or normothermic machine perfusion (HMP and NMP), use of oxygen carriers during storage, and supplemental compounds to storage solutions have emerged, offering potential benefits in preserving graft viability. This review explores the cellular and molecular mechanisms of ischemic injury in deceased donor kidneys, preservation strategies tested in preclinical models, and emerging therapeutic interventions aimed at improving adverse post-transplant outcomes.