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ID 116545
Title Alternative
Heparin cofactor II reduces albuminuria
Author
Uemoto, Ryoko Tokushima University
Sekine, Akiko Tokushima University
Mitsui, Yukari Tokushima University
Masuda, Shiho Tokushima University
Otoda, Toshiki Tokushima University
Honda, Soichi Minami Municipal National Insurance Hospital
Kondo, Akira Kondo Naika Hospital
Keywords
Albuminuria
Heparin cofactor II
Protease-Activated Receptors
Content Type
Journal Article
Description
Aims/Introduction: Thrombin exerts various pathophysiological functions by activating protease-activated receptors (PARs). Recent data have shown that PARs influence the development of glomerular diseases including diabetic kidney disease (DKD) by regulating inflammation. Heparin cofactor II (HCII) specifically inactivates thrombin; thus, we hypothesized that low plasma HCII activity correlates with DKD development, as represented by albuminuria.
Materials and Methods: Plasma HCII activity and spot urine biomarkers, including albumin and liver-type fatty acid-binding protein (L-FABP), were determined as the urine albumin-to-creatinine ratio (uACR) and the urine L-FABP-to-creatinine ratio (uL-FABPCR) in 310 Japanese patients with diabetes mellitus (176 males and 134 females). The relationships between plasma HCII activities and those DKD urine biomarkers were statistically evaluated. In addition, the relationship between plasma HCII activities and annual uACR changes was statistically evaluated for 201/310 patients (115 males and 86 females).
Results: The mean plasma HCII activity of all participants was 93.8 ± 17.7%. Multivariate-regression analysis including confounding factors showed that plasma HCII activity independently contributed to the suppression of the uACR and log-transformed uACR values (P = 0.036 and P = 0.006, respectively) but not uL-FABPCR (P = 0.541). In addition, plasma HCII activity significantly and inversely correlated with annual uACR and log-transformed uACR increments after adjusting for confounding factors (P = 0.001 and P = 0.014, respectively).
Conclusions: The plasma HCII activity was inversely and specifically associated with glomerular injury in patients with diabetes. The results suggest that HCII can serve as a novel predictive factor for early-stage DKD development, as represented by albuminuria.
Journal Title
Journal of Diabetes Investigation
ISSN
20401124
NCID
AA12488319
Publisher
Asian Association for the Study of Diabetes|John Wiley & Sons
Volume
12
Issue
12
Start Page
2172
End Page
2182
Published Date
2021-05-27
Rights
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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DOI (Published Version)
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language
eng
TextVersion
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departments
University Hospital
Medical Sciences
Institute of Advanced Medical Sciences
Oral Sciences