Figure 6. Proposed hypothesis for the sensitive biomarker of renal necrosis in AKI.

In healthy cells the transport of hyperpolarized [1,4-¹³C]fumarate across the cell membrane is slow compared to the decay of the hyperpolarized signal and thus no conversion to [1,4-¹³C]malate via fumarase is seen. In necrotic cells the plasma membrane is compromised and thus fumarase is freely available for the substrates [1,4-¹³C]fumarate and water to convert to [1,4-¹³C]malate. Additionally in the healthy rat little or no fumarase are present in blood or urine, however following AKI both blood and urine show necrosis dependent fumarase activity.