Characterizing Renal Tubular Epithelial Injury during Donation after Cardiocircualtory Death (DCD) and Possible Amelioration with PKX-001

Abstract

Deceased donor kidneys from Donation after Circulatory Death (DCD) contribute significantly to transplantation yet pose challenges due to ischemia-reperfusion injury (IRI). This study characterizes renal tubular epithelial injury during DCD and evaluates the protective potential of PKX-001, an antifreeze protein. Using a rat model, we simulated ischemia by prolonged cold preservation followed by warm preservation to mimic reperfusion injury. Biomarkers including NAG and cleaved caspase-3 quantified proximal tubular damage, supported by immunohistochemical staining for caspase-3 and KIM-1. Findings indicate increased proximal tubular damage with extended cold ischemic time, exacerbated by PKX-001 under static cold storage (SCS), contrasting with protective trends under hypothermic machine perfusion (HMP). Sex-based differences in susceptibility to tubular injury were noted, with female rats showing increased vulnerability. While PKX-001 shows promise in mitigating renal damage, its efficacy varies with preservation method. This study advances understanding of IRI in DCD grafts, highlighting the need for tailored interventions to improve outcomes and reduce healthcare costs associated with DCD kidney transplantation.