Metabolic Characterization of Deceased Donor Kidneys Undergoing Hypothermic Machine Perfusion Before Transplantation Using 13C-enriched Glucose.

Abstract

The provision of a metabolic substrate is one mechanism by which hypothermic machine perfusion (HMP) of kidneys provides clinical benefit. This study aimed to describe de novo metabolism in ex vivo human kidneys undergoing HMP before transplantation using 13C-labeled glucose as a metabolic tracer. Cadaveric human kidneys were perfused with modified clinical-grade perfusion fluid (kidney perfusion solution [KPS-1], Organ Recovery Systems), in which glucose was uniformly enriched with the stable isotope 13C ([U-13C] glucose). The sampled perfusion fluid was analyzed using a blood gas analyzer, and metabolic profiling was performed using 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy and mass spectrometry. Functional outcome measures included serum creatinine levels and the development of delayed graft function. Fourteen kidneys were perfused with the modified KPS-1 and successfully transplanted. The mean duration of HMP was 8.7 h. There was a sustained increase in the conversion of glucose into de novo glycolytic end products, such as lactate, in donor kidneys during HMP. There was no significant association between functional outcomes and metabolism during the HMP. De novo anaerobic metabolism was indicated by continuing lactate production, as indicated by increasing concentrations of universally 13C-labeled lactate ([U-13C] lactate) in perfusion fluid from all kidneys. This was more evident in donation after circulatory death donor kidneys. Our study is the first to use [U-13C] glucose to describe the metabolism during HMP. The consequences of an initial warm ischemic insult on circulatory death in donor kidneys continue during the preservation period.