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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 [ 13 C, 15 N] urea dynamics and 23 Na distribution before and 60 min after glucagon infusion in six female rats. Glucagon infusion increased the renal [ 13 C, 15 N] 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 13 C-urea enables monitoring of renal urinary excretion effects in vivo., (© 2018 John Wiley & Sons, Ltd.)

Purpose: In the current study, we investigated hyperpolarized urea as a possible imaging biomarker of the renal function by means of the intrarenal osmolality gradient., Methods: Hyperpolarized three-dimensional balanced steady state 13 C MRI experiments alongside kidney function parameters and quantitative polymerase chain reaction measurements was performed on two groups of rats, a streptozotocin type 1 diabetic group and a healthy control group., Results: A significant decline in intrarenal steepness of the urea gradient was found after 4 weeks of untreated insulinopenic diabetes in agreement with an increased urea transport transcription., Conclusion: MRI and hyperpolarized [ 13 C, 15 N]urea can monitor the changes in the corticomedullary urea concentration gradients in diabetic and healthy control rats. Magn Reson Med 77:1650-1655, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Early diabetic nephropathy is largely undetectable before substantial functional changes have occurred. In the present study, we investigated the distribution of electrolytes and urea in the early diabetic kidney in order to explore whether pathophysiological and metabolic changes appear concomitantly with a decreased sodium and urea gradient. By using hyperpolarized (13)C urea it was possible to measure the essential intrarenal electrolyte gradients and the acute changes following furosemide treatment. No differences in either intrarenal urea or sodium gradients were observed in early diabetes compared to healthy controls. These results indicate that the early metabolic and hypertrophic changes occurring in the diabetic kidney prelude the later functional alterations in diabetic kidney function, thus driving the increased metabolic demand commonly occurring in the diabetic kidney., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Purpose: Our aim was to assess a novel (13) C radial fast spin echo golden ratio single shot method for interrogating early renal changes in the diabetic kidney, using hyperpolarized (HP) [(13) C,(15) N2 ]urea as a T2 relaxation based contrast bio-probe., Methods: A novel HP (13) C MR contrast experiment was conducted in a group of streptozotocin type-1 diabetic rat model and age matched controls., Results: A significantly different relaxation time (P = 0.004) was found in the diabetic kidney (0.49 ± 0.03 s) compared with the controls (0.64 ± 0.02 s) and secondly, a strong correlation between the blood oxygen saturation level and the relaxation times were observed in the healthy controls., Conclusion: HP [(13) C,(15) N2 ]urea apparent T2 mapping may be a useful for interrogating local renal pO2 status and renal tissue alterations. Magn Reson Med, 2015. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., (© 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To assess the utility of Laplacian fitting to describe the differences in hyperpolarized [13C, 15N]urea T2 relaxation in ischemic and healthy rodent kidneys. Methods: Six rats with unilateral renal ischemia were investigated. [13C, 15N]Urea T2 mapping was undertaken with a radial fast spin echo method, with subsequent postprocessing performed with regularized Laplacian fitting. Results: Simulations showed that Laplacian fitting was stable down to a signal‐to‐noise ratio of 20. In vivo results showed a significant increase in the mono‐ and decrease in biexponential pools in ischemia reperfusion injury kidneys, in comparison to healthy (14 ± 10% versus 4 ± 2%, 85 ± 10% versus 95 ± 3%; P <.05). Conclusion: We demonstrate, for the first time, the differences in multiexponential behavior of [13C, 15N]urea between the healthy and ischemic rodent kidney. The distribution of relaxation pools were found to be both visually and numerically significantly different. The ability to improve the information level in hyperpolarized MR, by using the relaxation contrast mechanisms is an appealing option, that can easily be adopted in large animals and even in clinical studies in the near future. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the correlation between renal ischemia and 13C‐urea T2 relaxation rate in an acute kidney injury (AKI) rat model. Methods: Six rats subjected to unilateral renal ischemia were investigated. Creatinine clearance, urine output, plasma creatinine as well as blood‐urea nitrogen (BUN) values were acquired before and after the procedure. 1H T 2 * mapping was acquired using blood oxygenation level dependent (BOLD) MRI and hyperpolarized 13C‐urea T2 mapping was acquired using a 2D golden‐angle radial approach. Kidney perfusion was estimated using noncontrast flow alternating inversion recovery arterial spin labeling. Results: All rats showed clinical signs of AKI with increased plasma creatinine and increased BUN. Whole kidney 13C‐urea T2 significantly decreased 26% (P = 0.001) 24 h after reperfusion. A significantly different (3.7 times steeper; P = 0.008) osmolality gradient was observed in the contralateral kidney (P = 0.008; R2 = 0.86) compared with the postischemic kidney (P = 0.0004, R2=0.97). Whole kidney T 2 * signal (P = 0.14) and T 2 * gradient (P = 0.26) was similar between the two kidneys. Oxygen availability dependency on 13C‐urea T2 was investigated by means of the correlation between the BOLD and T2 signals; a statistically significant difference (P = 0.03) was found in the contralateral kidney (P = 0.0001; R2 = 0.95), but not in the postischemic kidney (P = 0.31; R2 = 0.25). Conclusion: We demonstrate that hyperpolarized [13C,15N2]urea T2 relaxation correlates with renal oxygen tension ( T 2 *) in the healthy contralateral kidney, but not in the postischemic kidney. The whole kidney T2 relaxation difference between the postischemic and contralateral kidney may originate from altered blood volume in the postischemic kidney. Magn Reson Med 80:696–702, 2018. © 2017 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

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 urea MRI during 60 min infusion of glucagon resulted in an increased 13C‐urea renal mean transit time for urea, without changing GFR, renal blood flow or renal oxygen tension. This change is related to the well‐known effect of increased urea excreation associated with the glucagon infusion, independent of renal functional effects. This study demonstrate that hyperpolarized 13C‐urea enables monitoring of renal urinary excretion effects in vivo. [ABSTRACT FROM AUTHOR]