Pyruvate-Enriched Anti-inflammatory Preservation of Explanted, Machine-Perfused Porcine Kidneys

Purpose: The gold-standard treatment for end-stage renal disease (ESRD) is kidney transplantation. Although the incidence of ESRD continues to mount, the supply of transplantable kidneys is woefully inadequate. Kidneys obtained from cardiac death victims are a potential source, but oxidative stress and inflammation predispose the organs to acute failure or delayed graft function after transplant. The intermediary metabolite pyruvate possesses energy-yielding, antioxidant and anti-inflammatory properties, and has been found to induce anti-inflammatory erythropoietin production in brain and heart. We postulate pyruvate-enriched preservation of machine-perfused kidneys will preserve organ integrity by increasing renal erythropoietin formation and dampening pro-inflammatory cytokine production. Methods: Kidneys are obtained from juvenile, Yorkshire pigs mechanically ventilated with 2and3% isoflurane. To model donation after cardiac death, the kidneys are harvested after induction of cardiac arrest and 60 minutes of ischemia in situ. After cold saline flush, the right kidney is explanted and perfused via the renal artery with standard organ preservation solution +/- 20 mM pyruvate in a LifePort® organ preservation system at 2-5°C for 72 h. Perfusate is sampled periodically for measurements of pro-inflammatory cytokines TNF-alpha and IL-6 and anti-inflammatory cytokines erythropoietin and IL-1beta. Results: The results are pending, as we are currently acquiring data. Conclusions: The conclusions are pending, but we expect hypothermic machine perfusion with pyruvate-enriched versus standard perfusate will suppress renal release of pro-inflammatory cytokines and increase anti-inflammatory cytokine formation, thereby blunting renal inflammation before transplant.