Metabolic MRI With Hyperpolarized 13 C-Pyruvate for Early Detection of Fibrogenic Kidney Metabolism.

Autor:	Bøgh N; From the MR Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark (N.B., L.B.B., C.W.R., S.K.B., T.H.T., I.K.M., E.S.S.H., C.L.); Department of Urology, Aarhus University Hospital, Aarhus, Denmark (A.K.K., M.G.M.); and Department of Pathology, Aalborg University Hospital, Aalborg, Denmark (F.H., A.W.)., Bertelsen LB, Rasmussen CW, Bech SK, Keller AK, Madsen MG, Harving F, Thorsen TH, Mieritz IK, Hansen ES, Wanders A, Laustsen C
Jazyk:	angličtina
Zdroj:	Investigative radiology [Invest Radiol] 2024 Dec 01; Vol. 59 (12), pp. 813-822. Date of Electronic Publication: 2024 Jun 25.
DOI:	10.1097/RLI.0000000000001094
Abstrakt:	Objectives: Fibrosis is the final common pathway for chronic kidney disease and the best predictor for disease progression. Besides invasive biopsies, biomarkers for its detection are lacking. To address this, we used hyperpolarized 13 C-pyruvate MRI to detect the metabolic changes associated with fibrogenic activity of myofibroblasts. Materials and Methods: Hyperpolarized 13 C-pyruvate MRI was performed in 2 pig models of kidney fibrosis (unilateral ureteral obstruction and ischemia-reperfusion injury). The imaging data were correlated with histology, biochemical, and genetic measures of metabolism and fibrosis. The porcine experiments were supplemented with cell-line experiments to inform the origins of metabolic changes in fibrogenesis. Lastly, healthy and fibrotic human kidneys were analyzed for the metabolic alterations accessible with hyperpolarized 13 C-pyruvate MRI. Results: In the 2 large animal models of kidney fibrosis, metabolic imaging revealed alterations in amino acid metabolism and glycolysis. Conversion from hyperpolarized 13 C-pyruvate to 13 C-alanine decreased, whereas conversion to 13 C-lactate increased. These changes were shown to reflect profibrotic activity in cultured epithelial cells, macrophages, and fibroblasts, which are important precursors of myofibroblasts. Importantly, metabolic MRI using hyperpolarized 13 C-pyruvate was able to detect these changes earlier than fibrosis-sensitive structural imaging. Lastly, we found that the same metabolic profile is present in fibrotic tissue from human kidneys. This affirms the translational potential of metabolic MRI as an early indicator of fibrogenesis associated metabolism. Conclusions: Our findings demonstrate the promise of hyperpolarized 13 C-pyruvate MRI for noninvasive detection of fibrosis development, which could enable earlier diagnosis and intervention for patients at risk of kidney fibrosis. Competing Interests: Conflicts of interest and sources of funding: This study was funded by The Lundbeck Foundation and The Karen Elise Jensen Foundation. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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