IL-1 Receptor Blockade Modulates Inflammation During Sequential Perfusion in Ex Vivo Porcine Kidneys

BACKGROUND: Donor shortage and suboptimal posttransplant outcomes highlight the need for improved organ recovery and preservation strategies. Ischemia-reperfusion injury remains a key challenge compromising kidney quality, particularly in marginal donors. Interleukin-1 (IL-1) family cytokines amplify sterile inflammatory responses during ischemia-reperfusion injury, further impairing organ viability. METHODS: We evaluated IL-1 receptor (IL-1R) antagonism with Anakinra during sequential machine perfusion in an ex vivo porcine kidney model. Kidneys (n = 24) underwent 30 min of warm ischemia followed by 24 h of hypothermic machine perfusion and 6 h of normothermic machine perfusion. Anakinra was administered either during hypothermic machine perfusion or during normothermic machine perfusion (n = 8 per treatment group) and compared with untreated controls. RESULTS: IL-1R blockade reduced renal expression of IL-1β, IL-1α, and IL-6 and lowered IL-1/IL-6 protein levels in perfusate and urine, accompanied by decreased sodium and lactate excretion. Perfusion flow, aspartate aminotransferase, lactate dehydrogenase, and tissue ATP were comparable between groups, whereas both Anakinra protocols were associated with higher creatinine clearance and metabolic coupling. CONCLUSIONS: In this ex vivo perfusion model, IL-1 pathway modulation attenuated inflammatory activation and was linked to better renal functional parameters during reperfusion. These findings support IL-1 signaling as a promising target for immunomodulation during machine perfusion and provide a rationale for further evaluation in transplant models.