IL-1 receptor antagonist anakinra downregulates inflammatory cytokines during renal normothermic machine perfusion: Preliminary results.

Abstract

The interleukin 1 (IL-1) cytokine group plays a key role in sterile inflammation and may be an important target for transplant-related renal injury. This study examined the effects of anakinra, a non-specific IL-1 receptor antagonist, administered during normothermic machine perfusion (NMP) of porcine kidneys. Paired porcine kidneys (n = 5 pairs) underwent 15 min of warm ischemia plus 2 h of static cold storage in ice. Kidneys were then perfused with autologous whole blood using an exvivo NMP platform. Kidneys were randomly allocated to receive anakinra or vehicle administered at the start of NMP. Cortical biopsies were collected at baseline before ischemic injury and at the end of NMP. Functional parameters were recorded and calculated, and inflammatory markers were measured by qPCR and ELISA techniques. During NMP, there were no statistically significant differences in renal blood flow, urine output, creatinine clearance or fractional excretion of sodium in the anakinra and control groups. The administration of anakinra significantly downregulated transcriptional expression of IL-6, Fas ligand and intercellular adhesion molecule 1 (p = 0.029, 0.029, 0.028, respectively). Anakinra, an IL-1 receptor blocker, successfully attenuated the downstream inflammatory and immune-mediated response within the kidney during NMP.