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

Ludimila Leite Marzochi^1,2, Heloisa Cristina Caldas^1,3, Dafni Efraimoglou²

¹Departamento de Medicina I, Laboratório de Imunologia e Transplante Experimental (LITEX), Faculdade de Medicina de São José do Rio Preto (FAMERP), São Paulo, Brazil.

Transplantation

|June 30, 2026

Summary

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Blocking the Interleukin-1 receptor (IL-1R) with Anakinra during machine perfusion improved kidney function in a porcine model. This strategy reduced inflammation and enhanced metabolic coupling, offering a promising approach for organ preservation.

Area of Science:

Transplantation immunology
Organ preservation
Renal physiology

Background:

Donor organ shortage and suboptimal transplant outcomes necessitate improved organ recovery and preservation.
Ischemia-reperfusion injury (IRI) significantly compromises kidney quality, especially from marginal donors.
Interleukin-1 (IL-1) family cytokines exacerbate sterile inflammatory responses during IRI, impairing organ viability.

Purpose of the Study:

To evaluate the efficacy of IL-1 receptor (IL-1R) antagonism using Anakinra during sequential machine perfusion in an ex vivo porcine kidney model.
To assess the impact of Anakinra on inflammatory markers and renal function following ischemia and machine perfusion.

Main Methods:

A porcine kidney model (n=24) underwent warm ischemia followed by hypothermic and normothermic machine perfusion.

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Anakinra was administered during either hypothermic or normothermic machine perfusion (n=8 per group).

Outcomes were compared to untreated control kidneys.

Main Results:

IL-1R blockade with Anakinra reduced renal expression of IL-1β, IL-1α, and IL-6, and lowered IL-1/IL-6 protein levels in perfusate and urine.
Anakinra treatment led to decreased sodium and lactate excretion.
Both Anakinra protocols demonstrated higher creatinine clearance and improved metabolic coupling compared to controls.

Conclusions:

Modulating the IL-1 pathway via IL-1R antagonism attenuated inflammatory activation in an ex vivo kidney perfusion model.
IL-1 pathway inhibition was associated with improved renal functional parameters during reperfusion.
These findings support IL-1 signaling as a viable target for immunomodulation in machine perfusion, warranting further investigation in transplant models.