Cold Ischemia Time in Kidney Transplantation: Pathophysiology, Clinical Impact, and Emerging Preservation Strategies – A Narrative Review

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Abstract
Chronic kidney disease remains a major global health burden, and kidney transplantation is the preferred treatment for patients with end-stage disease. Among the modifiable factors influencing graft outcomes, cold ischemia time (CIT) plays a central role in determining early allograft performance. Prolonged CIT exacerbates ischemia–reperfusion injury through metabolic depletion, oxidative stress, endothelial dysfunction, and innate immune activation, thereby increasing the risk of delayed graft function and subsequent graft impairment. This narrative review critically synthesizes current evidence on the pathophysiological mechanisms linking CIT to kidney graft dysfunction, as well as contemporary preservation strategies and emerging biomarkers of early injury. The literature consistently demonstrates a time-dependent association between prolonged CIT and adverse post-transplant outcomes, although effect magnitude varies according to donor profile and preservation method. In the context of expanding donor criteria and increasingly complex transplant logistics, optimization of CIT remains a key, potentially modifiable target to improve graft performance and resource utilization. Future studies integrating advanced preservation technologies and sensitive biomarkers are warranted to refine risk stratification and guide personalized graft management

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