Glucagon infusion alters the hyperpolarized ¹³C‐urea renal hemodynamic signature

Abstract

Renal urea handling is central to the urine concentrating mechanism, and as such the ability to image urea transport in the kidney is an important potential imaging biomarker for renal functional assessment. Glucagon levels associated with changes in dietary protein intake have been shown to influence renal urea handling; however, the exact mechanism has still to be fully understood. Here we investigate renal function and osmolite distribution using [13C,15N] urea dynamics and 23Na distribution before and 60 min after glucagon infusion in six female rats. Glucagon infusion increased the renal [13C,15N] urea mean transit time by 14%, while no change was seen in the sodium distribution, glomerular filtration rate or oxygen consumption. This change is related to the well‐known effect of increased urea excretion associated with glucagon infusion, independent of renal functional effects. This study demonstrates for the first time that hyperpolarized 13C‐urea enables monitoring of renal urinary excretion effects in vivo.

Hyperpolarized 13C MRI: A novel approach for probing cerebral metabolism in health and neurological disease

“…Early clinical studies have focused on the use of hyperpolarized pyruvate to probe both glycolysis and TCA metabolism for oncological, renal, and cardiac metabolism. [22][23][24][25][26][27][28][29][30][31] This review explores the application of 13 C-MRI to cerebral imaging and its future potential in the clinic.…”

The hemodynamic and metabolic effects of spironolactone treatment in acute kidney injury assessed by hyperpolarized MRI

“…The fact that the two non-metabolic perfusion tracers show different hemodynamic patterns might originate from the differences in handling of the two: one being an artificial non-physiologic molecule excreted by the kidneys and the other being an important osmolyte being actively reabsorbed besides being excreted by the kidneys. 23 We speculate that the surprising finding that the absolute perfusion did not agree between urea and gadolinium is likely linked to the acquisition strategies employed and/or the underlying hemodynamic handling. Further studies are needed to fully understand these inconsistencies.…”

Hyperpolarised 13C-MRI metabolic and functional imaging: an emerging renal MR diagnostic modality

“…By repurposing a kinetic analysis approach developed for 11 C-acetate PET, it is possible to map the metabolic clearance rate of 13 C-acetate, similar to that reported in 11 The intrarenal osmolality-gradient is driven by the active transport of ions and water and is closely linked to renal function. A particularly appealing emerging clinical probe for renal investigations is the osmolite 13 C-urea, which has been demonstrated in pre-clinical models to allow assessment of pathological changes in kidney diseases (28,32,61), as well as functional states such as the difference between hydration and diuresis (35,62,63). By utilising [ 13 C, 15 N]urea as a probe, it is possible to increase the longitudinal and transverse relaxation times (T1 and T2 relaxation) of the hyperpolarised state, and thus, [ 13 C, 15 N]urea could potentially be used in future clinical studies, thereby extending the imaging window (33).…”