Assessment of early diabetic renal changes with hyperpolarized [1‐13C]pyruvate

Abstract

This experimental study explores a novel magnetic resonance imaging/spectroscopic (MRI/MRS) method that measures changes in renal metabolism in a diabetic rat model. This hyperpolarized metabolic MRI/MRS method allows monitoring of metabolic processes in seconds by >10 000-fold enhancement of the MR signal. The method has shown that the conversion of pyruvate to bicarbonate, i.e. pyruvate dehydrogenase (PDH) activity, is significantly altered in the myocardium already at the onset of diabetes, and the predominant Warburg effect is a valuable cancer maker via the lactate dehydrogenase (LDH) activity. We hypothesize that a similar change in PDH and LDH could be found in the early diabetic kidney. In a streptozotocin rat model of type 1 diabetes, hyperpolarized (13) C-MRI and blood oxygenation level-dependent (1) H-MRI was employed to investigate the changes in renal metabolism in the diabetic and the control kidneys in vivo. The diabetic kidney showed a 149% increase in the lactate/pyruvate ratio compared with the control rat kidney, whereas the bicarbonate/pyruvate ratio was unchanged between the diabetic and the control rat kidneys, consistent with literature findings. These metabolic findings paralleled a reduced intrarenal oxygen availability as found by blood oxygenation level-dependent MRI. Hyperpolarized (13) C-MRI shows promise in the diagnosis and monitoring of early renal changes associated with diabetes, with the pyruvate/lactate ratio as an imaging biomarker for regional renal changes.