Pyruvate-Enriched Kidney Preservation for Transplant: Pilot Histology Study

Purpose: Hypothermic machine perfusion (HMP) has proven superior to Static Cold Storage (SCS) in preserving renal graft function, but HMP-preserved renal grafts still experience ischemia related injury. Inflammation, reactive oxygen species and depletion of ATP, all contribute to ischemia-induced damage in kidneys, and cause acute graft failure or delayed graft recovery in the recipient. Pyruvate has proven protective against ischemia-reperfusion injury of heart and brain. This study seeks to define the histopathological processes that porcine renal grafts incur during HMP and demonstrate the benefits of enriching perfusate solution with pyruvate. Methods: Laparotomy was performed on isoflurane-anesthetized Yorkshire pigs, and both kidneys excised. One kidney was immediately sectioned and samples of cortex and medulla were fixed in 10% formalin. The contralateral kidney underwent HMP in a LifePort organ preservation system at 2-5°C using University of Wisconsin (UW) solution containing 5 g/dl hetastarch ± 20 mM sodium pyruvate. At 72 h HMP, the kidney was sectioned and samples fixed in 10% formalin. Tissue samples were paraffin-embedded, sectioned and stained with hematoxylin-eosin for histological examination. Results: We expect kidneys preserved with pyruvate-enriched vs. standard UW solution will show less structural damage to renal parenchyma, particularly less extensive edema, brush border simplification, vacuolization, and tubular dilation. Conclusions: Pyruvate has proven protective against ischemia-induced organ damage by increasing ATP/ADP ratio, increasing endogenous antioxidants, suppressing inflammation, and inducing cytoprotective erythropoietin formation. Pyruvate-enriched HMP may afford robust renoprotection to improve function and reduce renal allografts failure.