Plasma heparin cofactor II activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes.
Adult
Aged
Albumins
/ metabolism
Albuminuria
/ blood
Biomarkers
/ blood
Creatinine
/ urine
Diabetes Mellitus, Type 1
/ blood
Diabetes Mellitus, Type 2
/ blood
Diabetic Nephropathies
/ etiology
Fatty Acid-Binding Proteins
/ urine
Female
Heparin Cofactor II
/ analysis
Humans
Male
Middle Aged
Receptors, Proteinase-Activated
/ blood
Regression Analysis
Thrombin
/ metabolism
Albuminuria
Heparin cofactor II
Protease-Activated Receptors
Journal
Journal of diabetes investigation
ISSN: 2040-1124
Titre abrégé: J Diabetes Investig
Pays: Japan
ID NLM: 101520702
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
revised:
10
05
2021
received:
03
03
2021
accepted:
20
05
2021
pubmed:
28
5
2021
medline:
28
1
2022
entrez:
27
5
2021
Statut:
ppublish
Résumé
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. 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). 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). 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.
Identifiants
pubmed: 34043882
doi: 10.1111/jdi.13602
pmc: PMC8668075
doi:
Substances chimiques
Albumins
0
Biomarkers
0
FABP1 protein, human
0
Fatty Acid-Binding Proteins
0
Receptors, Proteinase-Activated
0
SERPIND1 protein, human
0
Heparin Cofactor II
81604-65-1
Creatinine
AYI8EX34EU
Thrombin
EC 3.4.21.5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2172-2182Subventions
Organisme : Nippon Boehringer Ingelheim Co., Ltd.
Organisme : Ono Pharmaceutical Co., Ltd.
Organisme : Japan Society for the Promotion of Science KAKENHI
ID : 19K08680
Organisme : Teijin Pharma Ltd.
Informations de copyright
© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
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