Imaging aberrant oxidative and gluconeogenic metabolism in acute kidney injury using hyperpolarized [1-13C]pyruvate and [1,4-13C2]fumarate

Motivation: Clinical diagnosis and management of acute kidney injury rely on systemic blood biomarkers, lacking specificity and sensitivity of associated renal metabolism. Goal(s): To examine changes of renal oxidative and gluconeogenic metabolism induced by acute kidney injury. Approach: Hyperpolarized (HP) [1-13C]pyruvate and HP [1,4-13C2]fumarate were separately used to assess pyruvate dehydrogenase (PDH) and phosphoenolpyruvate carboxykinase (PEPCK) activities in rat kidneys with unilateral ischemia reperfusion injury. Results: [13C]Bicarbonate produced from HP [1-13C]pyruvate and HP [1,4-13C2]fumarate decreased, suggesting suppressed PDH flux and gluconeogenic pathway, respectively. Impact: The proposed imaging methods and biomarkers can be broadly applicable to other types of tissue injuries, as well as renal or hepatic diseases that affect metabolism.