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

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.