Relationship between renal oxidative stress levels and disease severity in patients with chronic kidney disease assessed by [Cu-64]ATSM PET/MRI

Abstract The purpose of the study was to investigate renal oxidative stress (OS) and its relationship with disease severity in patients with chronic kidney disease (CKD) using positron emission tomography coupled with magnetic resonance imaging (PET/MRI), employing 64Cu-diacetyl-bis(N4-methylthiosem...

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Main Authors: Ya’nan Huang, Yudai Nishikawa, Tetsuya Mori, Munenobu Nogami, Akira Makino, Yasushi Kiyono, Tadashi Toyama, Hidehiko Okazawa
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-85027-2
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author Ya’nan Huang
Yudai Nishikawa
Tetsuya Mori
Munenobu Nogami
Akira Makino
Yasushi Kiyono
Tadashi Toyama
Hidehiko Okazawa
author_facet Ya’nan Huang
Yudai Nishikawa
Tetsuya Mori
Munenobu Nogami
Akira Makino
Yasushi Kiyono
Tadashi Toyama
Hidehiko Okazawa
author_sort Ya’nan Huang
collection DOAJ
description Abstract The purpose of the study was to investigate renal oxidative stress (OS) and its relationship with disease severity in patients with chronic kidney disease (CKD) using positron emission tomography coupled with magnetic resonance imaging (PET/MRI), employing 64Cu-diacetyl-bis(N4-methylthiosemicarbazonate) (64Cu-ATSM) as the PET tracer for OS imaging. Thirty patients with CKD (66.4 ± 8.2 y.o.) and seven healthy controls (HC) subjects (58.3 ± 3.8 y.o.) underwent 64Cu-ATSM PET/MRI. Participants were categorized into three groups based on their estimated glomerular filtration rate (eGFR): HC, mild CKD (stages 2-3a), and advanced CKD (stages 3b-5). All subjects underwent 30-min dynamic PET/MRI starting with the injection of 64Cu-ATSM to evaluate renal blood flow (RBF) and OS levels. RBF (mL/min/100 g) images were calculated from the first 3 min PET data, and standardized uptake value (SUV) images were obtained from delayed frames of 15–30 min after injection. The 64Cu-ATSM SUV images were corrected to RBF-adjusted SUV using individual RBF images to estimate the OS levels of individual kidneys using the following equation: adjusted OS index (aOSi) = (SUV/RBF)x100. Significant correlation was observed between eGFR and RBF (r = 0.81, P < 0.001). RBF in patients with advanced CKD is significantly lower than that in HC (P < 0.001) and patients with mild CKD (P = 0.004). 64Cu-ATSM SUV did not differ significantly among the three groups (P = 0.171). 64Cu-ATSM SUVs did not correlate with creatinine in the HC subjects or in the patients with CKD. However, these values did correlate with eGFR (r = 0.33, P = 0.049) in all subjects, whereas the CKD patients showed no significant correlation. Following RBF correction, the aOSi demonstrated significant correlations with creatinine (r = 0.75, P < 0.001), eGFR (r= -0.65, P < 0.001), and CKD stages (r = 0.57, P < 0.001) in all subjects. This preliminary study has revealed that 64Cu-ATSM PET may provide a estimate of renal OS reasonably in CKD patients noninvasively. Increased aOSi values were correlated with the CKD stages and creatinine levels, suggesting that OS increases with the severity of renal dysfunction.
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spelling doaj-art-fc1a129f241c4e7bb1f182f09f7ccde92025-08-20T02:01:35ZengNature PortfolioScientific Reports2045-23222025-02-011511910.1038/s41598-024-85027-2Relationship between renal oxidative stress levels and disease severity in patients with chronic kidney disease assessed by [Cu-64]ATSM PET/MRIYa’nan Huang0Yudai Nishikawa1Tetsuya Mori2Munenobu Nogami3Akira Makino4Yasushi Kiyono5Tadashi Toyama6Hidehiko Okazawa7Biomedical Imaging Research Center, University of FukuiDepartment of Nephrology, Faculty of Medical Sciences, University of FukuiBiomedical Imaging Research Center, University of FukuiBiomedical Imaging Research Center, University of FukuiBiomedical Imaging Research Center, University of FukuiBiomedical Imaging Research Center, University of FukuiDepartment of Nephrology, Faculty of Medical Sciences, University of FukuiBiomedical Imaging Research Center, University of FukuiAbstract The purpose of the study was to investigate renal oxidative stress (OS) and its relationship with disease severity in patients with chronic kidney disease (CKD) using positron emission tomography coupled with magnetic resonance imaging (PET/MRI), employing 64Cu-diacetyl-bis(N4-methylthiosemicarbazonate) (64Cu-ATSM) as the PET tracer for OS imaging. Thirty patients with CKD (66.4 ± 8.2 y.o.) and seven healthy controls (HC) subjects (58.3 ± 3.8 y.o.) underwent 64Cu-ATSM PET/MRI. Participants were categorized into three groups based on their estimated glomerular filtration rate (eGFR): HC, mild CKD (stages 2-3a), and advanced CKD (stages 3b-5). All subjects underwent 30-min dynamic PET/MRI starting with the injection of 64Cu-ATSM to evaluate renal blood flow (RBF) and OS levels. RBF (mL/min/100 g) images were calculated from the first 3 min PET data, and standardized uptake value (SUV) images were obtained from delayed frames of 15–30 min after injection. The 64Cu-ATSM SUV images were corrected to RBF-adjusted SUV using individual RBF images to estimate the OS levels of individual kidneys using the following equation: adjusted OS index (aOSi) = (SUV/RBF)x100. Significant correlation was observed between eGFR and RBF (r = 0.81, P < 0.001). RBF in patients with advanced CKD is significantly lower than that in HC (P < 0.001) and patients with mild CKD (P = 0.004). 64Cu-ATSM SUV did not differ significantly among the three groups (P = 0.171). 64Cu-ATSM SUVs did not correlate with creatinine in the HC subjects or in the patients with CKD. However, these values did correlate with eGFR (r = 0.33, P = 0.049) in all subjects, whereas the CKD patients showed no significant correlation. Following RBF correction, the aOSi demonstrated significant correlations with creatinine (r = 0.75, P < 0.001), eGFR (r= -0.65, P < 0.001), and CKD stages (r = 0.57, P < 0.001) in all subjects. This preliminary study has revealed that 64Cu-ATSM PET may provide a estimate of renal OS reasonably in CKD patients noninvasively. Increased aOSi values were correlated with the CKD stages and creatinine levels, suggesting that OS increases with the severity of renal dysfunction.https://doi.org/10.1038/s41598-024-85027-2Oxidative stressChronic kidney disease64Cu-ATSMPET/MRI
spellingShingle Ya’nan Huang
Yudai Nishikawa
Tetsuya Mori
Munenobu Nogami
Akira Makino
Yasushi Kiyono
Tadashi Toyama
Hidehiko Okazawa
Relationship between renal oxidative stress levels and disease severity in patients with chronic kidney disease assessed by [Cu-64]ATSM PET/MRI
Scientific Reports
Oxidative stress
Chronic kidney disease
64Cu-ATSM
PET/MRI
title Relationship between renal oxidative stress levels and disease severity in patients with chronic kidney disease assessed by [Cu-64]ATSM PET/MRI
title_full Relationship between renal oxidative stress levels and disease severity in patients with chronic kidney disease assessed by [Cu-64]ATSM PET/MRI
title_fullStr Relationship between renal oxidative stress levels and disease severity in patients with chronic kidney disease assessed by [Cu-64]ATSM PET/MRI
title_full_unstemmed Relationship between renal oxidative stress levels and disease severity in patients with chronic kidney disease assessed by [Cu-64]ATSM PET/MRI
title_short Relationship between renal oxidative stress levels and disease severity in patients with chronic kidney disease assessed by [Cu-64]ATSM PET/MRI
title_sort relationship between renal oxidative stress levels and disease severity in patients with chronic kidney disease assessed by cu 64 atsm pet mri
topic Oxidative stress
Chronic kidney disease
64Cu-ATSM
PET/MRI
url https://doi.org/10.1038/s41598-024-85027-2
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