Assessment of early diabetic renal changes with hyperpolarized [1‐<sup>13</sup>C]pyruvate

Laustsen, Christoffer; Østergaard, Jakob Appel; Lauritzen, M.; Nørregaard, Rikke; Bowen, Sean; Søgaard, Lise Vejby; Flyvbjerg, Allan; Pedersen, Michael; Ardenkjær‐Larsen, Jan Henrik

doi:10.1002/dmrr.2370

Cited by 88 publications

(114 citation statements)

References 13 publications

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“…The diabetic kidney is, though, generally hypertrophic with an increased kidney weight early in the development toward diabetic nephropathy. However, this is without substantial alterations in the renal function albeit an increased oxygen consumption (20,21).…”

Section: Discussionmentioning

confidence: 99%

Diabetes induced renal urea transport alterations assessed with 3D hyperpolarized¹³C,¹⁵N-Urea

Bertelsen

Nielsen

et al. 2016

Magn. Reson. Med.

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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

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Section: Discussionmentioning

confidence: 99%

Diabetes induced renal urea transport alterations assessed with 3D hyperpolarized¹³C,¹⁵N-Urea

Bertelsen

Nielsen

et al. 2016

Magn. Reson. Med.

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“…Hyperpolarization of 13 C-labeled molecules remarkably enhances its sensitivity and allows noninvasive investigation of dynamic metabolic processes of the substrates. Using a hyperpolarized [1- 13 C]pyruvate, Laustsen et al has shown that reduction of inspired oxygen increases renal lactate and alanine formation in diabetic mice, while this effect is not observed in non-diabetic controls [41, 42], indicating that reduced oxygen availability alters renal energy metabolism in diabetes. Further, Keshari et al has assessed the oxidative stress in diabetic mouse kidneys using a hyperpolarized [1- 13 C] dehydroascorbate (DHA), a new endogenous redox sensor, and shown that redox capacity is decreased in diabetic kidneys prior to histological evidence of nephropathy and that angiotensin converting enzyme inhibition restores the renal redox status in diabetic mice [43].…”

Section: Assessment Of Renal Metabolismmentioning

confidence: 99%

Current MRI techniques for the assessment of renal disease

Takahashi

Wang²,

Quarles³

2015

Current Opinion in Nephrology and Hypertension

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Purpose of review Over the past decade a variety of magnetic resonance imaging (MRI) methods have been developed and applied to many kidney diseases. These MRI techniques show great promise, enabling the noninvasive assessment of renal structure, function, and injury in individual subjects. This review will highlight current applications of functional MRI techniques for the assessment of renal disease and discuss future directions. Recent findings Many pathological (functional and structural) changes or factors in renal disease can be assessed by advanced MRI techniques. These include renal vascular structure and function (contrast-enhanced MRI, arterial spin labeling), tissue oxygenation (blood oxygen level-dependent MRI), renal tissue injury and fibrosis (diffusion or magnetization transfer imaging, MR elastography), renal metabolism (chemical exchange saturation transfer, spectroscopic imaging), nephron endowment (cationic-contrast imaging), sodium concentration (23Na-MRI), and molecular events (targeted-contrast imaging). Summary Current advances in MRI techniques have enabled the non-invasive investigation of renal disease. Further development, evaluation, and application of the MRI techniques should facilitate better understanding and assessment of renal disease and the development of new imaging biomarkers, enabling the intensified treatment to high-risk populations and a more rapid interrogation of novel therapeutic agents and protocols.

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“…The observable conversion of HP substrate [1][2][3][4][5][6][7][8][9][10][11][12][13] C]pyruvate to HP [1-13 C]lactate catalyzed by lactate dehydrogenase (LDH) has generated particular interest as a glycolytic marker, with promising applications in cancer (4), cardiovascular disease (5,6), and diabetes (7), including a recent "first-in-man" HP 13 C MRI clinical Phase 1 safety trial in prostate cancer patients (8).…”

Section: Introductionmentioning

confidence: 99%

Hyperpolarized [¹³ C]ketobutyrate, a molecular analog of pyruvate with modified specificity for LDH isoforms

et al. 2016

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Purpose-The purpose of this study was to investigate 13 C hyperpolarization of α-ketobutyrate (αKB), an endogenous molecular analog of pyruvate, and its in vivo enzymatic conversion via lactate dehydrogenase (LDH), using localized MR spectroscopy.Methods-Hyperpolarized (HP) 13 C MR experiments were conducted using [ 13 C]αKB with rats in vivo and with isolated LDH enzyme in vitro, along with comparative experiments using [ 13 C]pyruvate. Based on differences in the kinetics of its reaction with individual LDH isoforms, HP [ 13 C]αKB was investigated as a novel MR probe with added specificity for activity of LDHB expressed H ("heart"-type) subunits of LDH (e.g. constituents of LDH-1 isoform).Results-Comparable T 1 and polarization values to pyruvate were attained (T 1 = 52s at 3T, polarization= 10%, at C 1 ). MR experiments showed rapid enzymatic conversion with substantially increased specificity. Formation of product HP [ 13 C]α-hydroxybutyrate (αHB) from αKB in vivo was increased 2.7-fold in cardiac slabs relative to liver and kidney slabs. In vitro studies resulted in 5.0-fold higher product production from αKB with bovine heart LDH-1, as compared with pyruvate.Conclusions-HP [ 13 C]αKB may be a useful MR probe of cardiac metabolism and other applications where the role of H subunits of LDH is significant (e.g. renal cortex and brain).

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

Abstract: 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.

Cited by 88 publications

References 13 publications

Diabetes induced renal urea transport alterations assessed with 3D hyperpolarized¹³C,¹⁵N-Urea

Diabetes induced renal urea transport alterations assessed with 3D hyperpolarized¹³C,¹⁵N-Urea

Current MRI techniques for the assessment of renal disease

Hyperpolarized [¹³ C]ketobutyrate, a molecular analog of pyruvate with modified specificity for LDH isoforms

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

Abstract: 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.

Cited by 88 publications

References 13 publications

Diabetes induced renal urea transport alterations assessed with 3D hyperpolarized13C,15N-Urea

Diabetes induced renal urea transport alterations assessed with 3D hyperpolarized13C,15N-Urea

Current MRI techniques for the assessment of renal disease

Hyperpolarized [13 C]ketobutyrate, a molecular analog of pyruvate with modified specificity for LDH isoforms

Contact Info

Product

Resources

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

Diabetes induced renal urea transport alterations assessed with 3D hyperpolarized¹³C,¹⁵N-Urea

Diabetes induced renal urea transport alterations assessed with 3D hyperpolarized¹³C,¹⁵N-Urea

Hyperpolarized [¹³ C]ketobutyrate, a molecular analog of pyruvate with modified specificity for LDH isoforms