Plasma Xanthine Oxidoreductase Activity Associated with Glycemic Control in Patients with Pre-Dialysis Chronic Kidney Disease

Introduction: Xanthine oxidoreductase (XOR) activity plays an important role as a pivotal source of reactive oxygen species, which is associated with cardiovascular disease (CVD) events. Patients with CKD have increased risk of CVD events. In the present study, factors associated with plasma XOR act...

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Main Authors: Shinya Nakatani, Eiji Ishimura, Takayo Murase, Takashi Nakamura, Ayumi Nakatani, Norikazu Toi, Kozo Nishide, Hideki Uedono, Akihiro Tsuda, Masafumi Kurajoh, Shinsuke Yamada, Katsuhito Mori, Masaaki Inaba, Masanori Emoto
Format: Article
Language:English
Published: Karger Publishers 2021-06-01
Series:Kidney & Blood Pressure Research
Subjects:
Online Access:https://www.karger.com/Article/FullText/516610
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author Shinya Nakatani
Eiji Ishimura
Takayo Murase
Takashi Nakamura
Ayumi Nakatani
Norikazu Toi
Kozo Nishide
Hideki Uedono
Akihiro Tsuda
Masafumi Kurajoh
Shinsuke Yamada
Katsuhito Mori
Masaaki Inaba
Masanori Emoto
author_facet Shinya Nakatani
Eiji Ishimura
Takayo Murase
Takashi Nakamura
Ayumi Nakatani
Norikazu Toi
Kozo Nishide
Hideki Uedono
Akihiro Tsuda
Masafumi Kurajoh
Shinsuke Yamada
Katsuhito Mori
Masaaki Inaba
Masanori Emoto
author_sort Shinya Nakatani
collection DOAJ
description Introduction: Xanthine oxidoreductase (XOR) activity plays an important role as a pivotal source of reactive oxygen species, which is associated with cardiovascular disease (CVD) events. Patients with CKD have increased risk of CVD events. In the present study, factors associated with plasma XOR activity in pre-dialysis CKD patients were investigated. Methods: In this cross-sectional study, plasma XOR activity in 118 pre-dialysis CKD patients (age 68 [57–75] years; 64 males, 26 with diabetes mellitus [DM]) was determined using a newly established highly sensitive assay based on (13C2,15N2) xanthine and liquid chromatography/triple quadrupole mass spectrometry. Results: Plasma glucose, hemoglobin A1c, and estimated glomerular filtration (eGFR) were significantly and positively correlated with plasma logarithmically transformed XOR (ln-XOR) activity. In multiple regression analyses, eGFR and hemoglobin A1c or plasma glucose were significantly, independently, and positively associated with plasma ln-XOR activity after adjusting for several confounders. Plasma XOR activity was significantly higher in CKD patients with (n = 26) than in those without (n = 92) DM (62.7 [32.3–122] vs. 25.7 [13.4–45.8] pmol/h/mL, p < 0.001). A total of 38 patients were taking uric acid-lowering drugs. Multiple regression analysis of CKD patients not administered uric acid-lowering drugs (n = 80) showed no significant association between eGFR and plasma ln-XOR activity. In contrast, association between glycemic control and plasma ln-XOR activity was significant even in CKD patients without uric acid-lowering drug treatment. Conclusions: These results indicate the importance of glycemic control in CKD patients in regard to decreased XOR, possibly leading to a decrease in CVD events.
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spelling doaj.art-882587d59e744151a580b1ae6b41f0882022-12-21T19:24:59ZengKarger PublishersKidney & Blood Pressure Research1420-40961423-01432021-06-011910.1159/000516610516610Plasma Xanthine Oxidoreductase Activity Associated with Glycemic Control in Patients with Pre-Dialysis Chronic Kidney DiseaseShinya Nakatani0Eiji Ishimura1Takayo Murase2Takashi Nakamura3Ayumi Nakatani4Norikazu Toi5Kozo Nishide6Hideki Uedono7Akihiro Tsuda8Masafumi Kurajoh9Shinsuke Yamada10Katsuhito Mori11Masaaki Inaba12Masanori Emoto13Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, JapanDepartment of Nephrology, Osaka City University Graduate School of Medicine, Osaka, JapanMie Research Laboratories, Sanwa Kagaku Kenkyusho Co., Ltd., Inabe-shi, JapanMie Research Laboratories, Sanwa Kagaku Kenkyusho Co., Ltd., Inabe-shi, JapanDepartment of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, JapanDepartment of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, JapanDepartment of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, JapanDepartment of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, JapanDepartment of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, JapanDepartment of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, JapanDepartment of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, JapanDepartment of Nephrology, Osaka City University Graduate School of Medicine, Osaka, JapanDepartment of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, JapanDepartment of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, JapanIntroduction: Xanthine oxidoreductase (XOR) activity plays an important role as a pivotal source of reactive oxygen species, which is associated with cardiovascular disease (CVD) events. Patients with CKD have increased risk of CVD events. In the present study, factors associated with plasma XOR activity in pre-dialysis CKD patients were investigated. Methods: In this cross-sectional study, plasma XOR activity in 118 pre-dialysis CKD patients (age 68 [57–75] years; 64 males, 26 with diabetes mellitus [DM]) was determined using a newly established highly sensitive assay based on (13C2,15N2) xanthine and liquid chromatography/triple quadrupole mass spectrometry. Results: Plasma glucose, hemoglobin A1c, and estimated glomerular filtration (eGFR) were significantly and positively correlated with plasma logarithmically transformed XOR (ln-XOR) activity. In multiple regression analyses, eGFR and hemoglobin A1c or plasma glucose were significantly, independently, and positively associated with plasma ln-XOR activity after adjusting for several confounders. Plasma XOR activity was significantly higher in CKD patients with (n = 26) than in those without (n = 92) DM (62.7 [32.3–122] vs. 25.7 [13.4–45.8] pmol/h/mL, p < 0.001). A total of 38 patients were taking uric acid-lowering drugs. Multiple regression analysis of CKD patients not administered uric acid-lowering drugs (n = 80) showed no significant association between eGFR and plasma ln-XOR activity. In contrast, association between glycemic control and plasma ln-XOR activity was significant even in CKD patients without uric acid-lowering drug treatment. Conclusions: These results indicate the importance of glycemic control in CKD patients in regard to decreased XOR, possibly leading to a decrease in CVD events.https://www.karger.com/Article/FullText/516610xanthine oxidoreductase activitychronic kidney diseasediabetes mellitus
spellingShingle Shinya Nakatani
Eiji Ishimura
Takayo Murase
Takashi Nakamura
Ayumi Nakatani
Norikazu Toi
Kozo Nishide
Hideki Uedono
Akihiro Tsuda
Masafumi Kurajoh
Shinsuke Yamada
Katsuhito Mori
Masaaki Inaba
Masanori Emoto
Plasma Xanthine Oxidoreductase Activity Associated with Glycemic Control in Patients with Pre-Dialysis Chronic Kidney Disease
Kidney & Blood Pressure Research
xanthine oxidoreductase activity
chronic kidney disease
diabetes mellitus
title Plasma Xanthine Oxidoreductase Activity Associated with Glycemic Control in Patients with Pre-Dialysis Chronic Kidney Disease
title_full Plasma Xanthine Oxidoreductase Activity Associated with Glycemic Control in Patients with Pre-Dialysis Chronic Kidney Disease
title_fullStr Plasma Xanthine Oxidoreductase Activity Associated with Glycemic Control in Patients with Pre-Dialysis Chronic Kidney Disease
title_full_unstemmed Plasma Xanthine Oxidoreductase Activity Associated with Glycemic Control in Patients with Pre-Dialysis Chronic Kidney Disease
title_short Plasma Xanthine Oxidoreductase Activity Associated with Glycemic Control in Patients with Pre-Dialysis Chronic Kidney Disease
title_sort plasma xanthine oxidoreductase activity associated with glycemic control in patients with pre dialysis chronic kidney disease
topic xanthine oxidoreductase activity
chronic kidney disease
diabetes mellitus
url https://www.karger.com/Article/FullText/516610
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