Journal of Diabetes Investigation (Dec 2021)

Plasma heparin cofactor II activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes

  • Tomoyo Hara,
  • Ryoko Uemoto,
  • Akiko Sekine,
  • Yukari Mitsui,
  • Shiho Masuda,
  • Kiyoe Kurahashi,
  • Sumiko Yoshida,
  • Toshiki Otoda,
  • Tomoyuki Yuasa,
  • Akio Kuroda,
  • Yasumasa Ikeda,
  • Itsuro Endo,
  • Soichi Honda,
  • Katsuhiko Yoshimoto,
  • Akira Kondo,
  • Toshiaki Tamaki,
  • Toshio Matsumoto,
  • Munehide Matsuhisa,
  • Masahiro Abe,
  • Ken‐ichi Aihara

DOI
https://doi.org/10.1111/jdi.13602
Journal volume & issue
Vol. 12, no. 12
pp. 2172 – 2182

Abstract

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Abstract 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.

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