Early detection of diabetic nephropathy using compartment-specific hyperpolarized 13C metabolic readouts

Motivation: There is a pressing need for new non-invasive markers of diabetic kidney disease. Goal(s): Our goal is to demonstrate that hyperpolarized (HP) 13C MRI can detect early metabolic indicators of diabetic nephropathy. Approach: We conducted serial HP 13C imaging studies of rats with uncontrolled diabetes using co-HP [1-13C]pyruvate and [1,3-13C2]acetoacetate for cellular compartment-specific metabolic measurements, in comparison with conventional serum markers of kidney function. Results: Metabolic conversions of HP substrates showed large, compartment-specific shifts in diabetic kidney over time, as compared with conventional serum markers. These metabolic changes indicate a progressive deficit of oxygen metabolism in diabetic kidney. Impact: Precise metabolic measurements obtained non-invasively by HP 13C MRI with multiple co-HP metabolic substrates, whose activities are localized to distinct cellular compartments, could enable early detection of diabetic kidney damage.