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Plasma heparin cofactor II activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes
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)...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8668075/ https://www.ncbi.nlm.nih.gov/pubmed/34043882 http://dx.doi.org/10.1111/jdi.13602 |
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author | Hara, Tomoyo Uemoto, Ryoko Sekine, Akiko Mitsui, Yukari Masuda, Shiho Kurahashi, Kiyoe Yoshida, Sumiko Otoda, Toshiki Yuasa, Tomoyuki Kuroda, Akio Ikeda, Yasumasa Endo, Itsuro Honda, Soichi Yoshimoto, Katsuhiko Kondo, Akira Tamaki, Toshiaki Matsumoto, Toshio Matsuhisa, Munehide Abe, Masahiro Aihara, Ken‐ichi |
author_facet | Hara, Tomoyo Uemoto, Ryoko Sekine, Akiko Mitsui, Yukari Masuda, Shiho Kurahashi, Kiyoe Yoshida, Sumiko Otoda, Toshiki Yuasa, Tomoyuki Kuroda, Akio Ikeda, Yasumasa Endo, Itsuro Honda, Soichi Yoshimoto, Katsuhiko Kondo, Akira Tamaki, Toshiaki Matsumoto, Toshio Matsuhisa, Munehide Abe, Masahiro Aihara, Ken‐ichi |
author_sort | Hara, Tomoyo |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8668075 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86680752021-12-21 Plasma heparin cofactor II activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes Hara, Tomoyo Uemoto, Ryoko Sekine, Akiko Mitsui, Yukari Masuda, Shiho Kurahashi, Kiyoe Yoshida, Sumiko Otoda, Toshiki Yuasa, Tomoyuki Kuroda, Akio Ikeda, Yasumasa Endo, Itsuro Honda, Soichi Yoshimoto, Katsuhiko Kondo, Akira Tamaki, Toshiaki Matsumoto, Toshio Matsuhisa, Munehide Abe, Masahiro Aihara, Ken‐ichi J Diabetes Investig Articles 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. John Wiley and Sons Inc. 2021-06-23 2021-12 /pmc/articles/PMC8668075/ /pubmed/34043882 http://dx.doi.org/10.1111/jdi.13602 Text en © 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Articles Hara, Tomoyo Uemoto, Ryoko Sekine, Akiko Mitsui, Yukari Masuda, Shiho Kurahashi, Kiyoe Yoshida, Sumiko Otoda, Toshiki Yuasa, Tomoyuki Kuroda, Akio Ikeda, Yasumasa Endo, Itsuro Honda, Soichi Yoshimoto, Katsuhiko Kondo, Akira Tamaki, Toshiaki Matsumoto, Toshio Matsuhisa, Munehide Abe, Masahiro Aihara, Ken‐ichi Plasma heparin cofactor II activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes |
title | Plasma heparin cofactor II activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes |
title_full | Plasma heparin cofactor II activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes |
title_fullStr | Plasma heparin cofactor II activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes |
title_full_unstemmed | Plasma heparin cofactor II activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes |
title_short | Plasma heparin cofactor II activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes |
title_sort | plasma heparin cofactor ii activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8668075/ https://www.ncbi.nlm.nih.gov/pubmed/34043882 http://dx.doi.org/10.1111/jdi.13602 |
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