Abstract
Xanthine oxidoreductase activity (XOR-a) plays an important role as a pivotal source of reactive oxygen species. In the present study, we investigated factors associated with plasma XOR-a in 163 hemodialysis patients (age 67.3 ± 10.9 years; 89 males and 74 females), using a newly established, highly-sensitive assay based on [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Plasma glucose and serum uric acid levels correlated significantly and positively with plasma XOR-a. In multiple regression analyses, the presence of type 2 diabetes mellitus (T2DM) and plasma glucose were associated significantly, independently, and positively with plasma XOR-a. While serum uric acid correlated significantly and positively with plasma XOR-a in hemodialysis patients without T2DM, plasma glucose and serum glycated albumin, a new marker of glycemic control in diabetic hemodialysis patients, correlated significantly and positively with plasma XOR-a in those with T2DM. Multivariate analyses in those with T2DM revealed that plasma glucose and serum glycated albumin were associated significantly and independently with plasma XOR-a, and that serum uric acid was associated significantly and independently with XOR-a in those without T2DM. Our results suggested that glycemic control in hemodialysis patients may be important in regard to a decrease in ROS induced by XOR.
Highlights
Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are strongly associated with cardiovascular disease (CVD)[1]
We investigated factors associated with plasma Xanthine oxidoreductase (XOR) activity in hemodialysis patients, using a newly established, highly-sensitive assay based on [13C2,15N2] xanthine and LC/triple quadrupole mass spectrometer (TQMS)
Our findings suggest the importance of determining uric acid level in hemodialysis patients without type 2 DM and plasma glucose level in hemodialysis patients with type 2 DM in regard to plasma XOR activity
Summary
Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are strongly associated with cardiovascular disease (CVD)[1]. It is clinically important to measure XOR activity in high-risk CVD populations, i.e., CKD and ESRD patients. There has been no previous investigation of the relationship between plasma XOR activity and clinical parameters in ESRD patients. We have developed a novel method to measure XOR activity in human plasma utilizing stable isotope-labeled [13C2,15N2] xanthine and liquid chromatography mass spectrometry, comprised of a Nano Space SI-2 LC system(LC/MS) and a TSQ-Quantum triple quadrupole mass spectrometer (TQMS). This assay provides highly accurate and highly sensitive measurements of human plasma XOR activity under physiologically equivalent conditions[9,10]. Hemodialysis patients, in which we measured plasma XOR activity using the newly developed method, and examined the relationship between plasma XOR activity and the clinical parameters
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