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

Nakatani, Shinya; Ishimura, Eiji; Murase, Takayo; Nakamura, Takashi; Nakatani, Ayumi; Toi, Norikazu; Nishide, Kozo; Uedono, Hideki; Tsuda, Akihiro; Kurajoh, Masafumi; Yamada, Shinsuke; Mori, Katsuhito; Inaba, Masaaki; Emoto, Masanori

doi:10.1159/000516610

Cited by 10 publications

(6 citation statements)

References 49 publications

(65 reference statements)

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“…A correlation has been suggested between eGFR and serum XOD activity in patients with chronic kidney disease (CKD) before dialysis, as well as in obese subjects. [15] Taken together with the results of the present study, these observations suggest that, in the population with normal renal function, XOD level is higher in those with higher than lower eGFR. After oral administration of inosine, the higher XOD level in the high-eGFR group transformed the exogenous purine into urate at a faster rate.…”

Section: Discussionsupporting

confidence: 85%

Purine Metabolic Pathway Alterations and Serum Urate Changes after Oral Inosine Loading in Male Chinese Volunteers

Liang,

Wu,

Gao

et al. 2023

Molecular Nutrition Food Res

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BackgroundOral inosine loading is a new method to evaluate the effects of purine on urate metabolism. However, individuals respond differently to acute purine intake, and the effects on the metabolism of other purines remain to be explored.Methods35 male participants are recruited. Participants received 500 mg of inosine orally after an overnight fast, and blood and urine samples are collected before and at various time points over 180 min after inosine administration.ResultsThe serum urate concentration is significantly different between the hyperuricemia (n = 14) and non‐hyperuricemia (n = 16) groups before inosine intake, but there is no in urate change after inosine intake. When grouped according to the baseline estimated glomerular filtration rate (eGFR), the increase in urate level in the high‐eGFR group is significantly higher than that in the low‐eGFR group (p = 0.047). The high‐eGFR group showed higher levels of serum xanthine and xanthine oxidase (XOD), the key enzyme in urate synthesis, after inosine loading (p < 0.01).ConclusionsThe increase in urate level is positively related to eGFR after oral acute inosine administration, which may have been due to a higher level of XOD.

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Section: Discussionsupporting

confidence: 85%

Purine Metabolic Pathway Alterations and Serum Urate Changes after Oral Inosine Loading in Male Chinese Volunteers

Liang,

Wu,

Gao

et al. 2023

Molecular Nutrition Food Res

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“…Therefore, XOR inhibition can reduce the oxidative stress related to organ damage from renal failure. A positive correlation between XOR activity and serum creatinine levels in CKD patients has been reported [30]. There was a negative correlation between XOR activity and eGFR in patients with chronic heart failure [31].…”

Section: Discussionmentioning

confidence: 79%

Association between Plasma Xanthine Oxidoreductase Activity and the Renal Function in a General Japanese Population: The Tohoku Medical Megabank Community-Based Cohort Study

Taguchi

Nasu

Satoh

et al. 2022

Kidney Blood Press Res

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Introduction: Xanthine oxidoreductase (XOR) has been identified as a critical source of reactive oxygen species in various pathophysiological conditions, including hypertension, endothelial dysfunction and atherosclerosis. This study investigated the association between XOR and renal function in a general Japanese population. Methods: The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a community-based cohort study in Iwate prefecture. Chronic kidney disease (CKD) was estimated using the estimated glomerular filtration rate of cystatin C (eGFRcys). Individuals with a history of hyperuricemia or severe renal dysfunction (eGFRcys < 15 ml/min/1.73 m2 or undergoing dialysis) were excluded from the study. We performed a multinominal multivariate logistic analysis adjusted for age, blood pressure, uric acid, glycated hemoglobin A1c, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol to associate XOR activity and renal function. Results: The present study included 4,248 participants (male/female: 1,373/2,875, age: 62.9 ± 11.7 years). When participants were divided according to XOR quartiles, blood pressure, body mass index, uric acid, low-density lipoprotein cholesterol and glycated hemoglobin A1c were highest in the highest XOR quartile (all p < 0.001). The XOR activity was significantly higher in the subgroup with CKD stage G3 and G4 (G1 vs. G2 vs. G3-G4: 44.8 ± 40.5 vs 52.0 ± 42.9 vs. 54.1 ± 43.9 pmol / h / mL, p = 0.02). The higher XOR activity was significantly associated with an increase of CKD stage: the odd ratios (95% confidence intervals) per 1 pmol/h/mL increase in XOR activity with CKD stage G1 as a reference were 1.37 (1.13-1.73) in G2 and 1.51 (1.30-1.84) in G3-G4. Conclusion: The present study concluded that high XOR activity was associated with the severity of CKD in a general Japanese population, suggesting that upregulated XOR activity may be involved in advanced renal dysfunction.

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“…A study of 118 patients with CKD showed that estimated glomerular filtration (eGFR) and levels of HbA1c or plasma glucose were significantly, independently, and positively associated with plasma XOR activity after adjusting for several confounders; in addition, plasma XOR activity was significantly higher in diabetic CKD patients than in those without diabetes, and the relationship between glycemic control and plasma XOR activity was significant even in CKD patients without uric acid-lowering drug treatment. The findings of this study suggest that glycemic control in CKD patients in regard to decreased XOR is important and could possibly lead to a decrease in CVD events [ 65 ]. A prospective study of 101 patients with CKD or on chronic hemodialysis who were followed for up to three years showed that the serum level of XOR activity, but not UA, was an independent predictor of cardiovascular events.…”

Section: Plasma Xor Activity and Cardiovascular Events In Patients Wi...mentioning

confidence: 99%

Human Plasma Xanthine Oxidoreductase Activity in Cardiovascular Disease: Evidence from a Population-Based Study

et al. 2023

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Xanthine oxidoreductase (XOR) and its products contribute to the development of chronic inflammation and oxidative stress. Excessive XOR activity is believed to promote inflammatory responses and atherosclerotic plaque formation, which are major cardiovascular risk factors. The mechanisms of XOR activity in the development and progression of cardiovascular disease (CVD), coupled with the complexity of the relationship between XOR activity and the biological effects of uric acid; reactive oxygen species; and nitric oxide, which are the major products of XOR activity, have long been debated, but have not yet been clearly elucidated. Recently, a system for measuring highly sensitive XOR activity in human plasma was established, and there has been progress in the research on the mechanisms of XOR activity. In addition, there are accumulating findings about the relationship between XOR activity and CVD. In this narrative review, we summarize existing knowledge regarding plasma XOR activity and its relationship with CVD and discuss future perspectives.

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

Cited by 10 publications

References 49 publications

Purine Metabolic Pathway Alterations and Serum Urate Changes after Oral Inosine Loading in Male Chinese Volunteers

Purine Metabolic Pathway Alterations and Serum Urate Changes after Oral Inosine Loading in Male Chinese Volunteers

Association between Plasma Xanthine Oxidoreductase Activity and the Renal Function in a General Japanese Population: The Tohoku Medical Megabank Community-Based Cohort Study

Human Plasma Xanthine Oxidoreductase Activity in Cardiovascular Disease: Evidence from a Population-Based Study

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