{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:09:59Z","timestamp":1787015399652,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/Introduction<\/jats:title>\n                    <jats:p>Thrombin exerts various pathophysiological functions by activating protease\u2010activated 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Plasma HCII activity and spot urine biomarkers, including albumin and liver\u2010type fatty acid\u2010binding protein (L\u2010FABP), were determined as the urine albumin\u2010to\u2010creatinine ratio (uACR) and the urine L\u2010FABP\u2010to\u2010creatinine ratio (uL\u2010FABPCR) 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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The mean plasma HCII activity of all participants was 93.8\u2009\u00b1\u200917.7%. Multivariate\u2010regression analysis including confounding factors showed that plasma HCII activity independently contributed to the suppression of the uACR and log\u2010transformed uACR values (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.036 and\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.006, respectively) but not uL\u2010FABPCR (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.541). In addition, plasma HCII activity significantly and inversely correlated with annual uACR and log\u2010transformed uACR increments after adjusting for confounding factors (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.001 and\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.014, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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\u2010stage DKD development, as represented by albuminuria.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdi.13602","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T13:51:37Z","timestamp":1622123497000},"page":"2172-2182","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Plasma heparin cofactor II activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes"],"prefix":"10.1111","volume":"12","author":[{"given":"Tomoyo","family":"Hara","sequence":"first","affiliation":[{"name":"Department of Hematology, Endocrinology and Metabolism Tokushima University Graduate School of Biomedical Sciences Tokushima 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Metabolism Tokushima University Graduate School of Biomedical Sciences Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoe","family":"Kurahashi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Endocrinology and Metabolism Tokushima University Graduate School of Biomedical Sciences Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumiko","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Hematology, Endocrinology and Metabolism Tokushima University Graduate School of Biomedical Sciences Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Otoda","sequence":"additional","affiliation":[{"name":"Department of Community Medicine and Medical Science Tokushima University Graduate School of Biomedical Sciences Tokushima 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