Ann Lab Med.  2017 Mar;37(2):155-158. 10.3343/alm.2017.37.2.155.

Effect of Vitamin D Status on Von Willebrand Factor and ADAMTS13 in Diabetic Patients on Chronic Hemodialysis

Affiliations
  • 1Renal Physiology Laboratory, Department of Nephrology and Hypertension, Meir Medical Center, Kfar Saba, Israel. tali.gal@clalit.org.il
  • 2Medical Laboratories, Meir Medical Center, Kfar Saba, Israel.
  • 3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Abstract

Von Willebrand factor (vWF) is a glycoprotein with a crucial role in the formation of platelet thrombi, and ADAMTS13 is the main enzyme responsible for vWF cleavage. Both are important in the relationship between diabetic nephropathy, hypercoagulability, and cardiovascular disease. This study evaluated a potential relationship between vitamin D (vitD) levels, vWF, ADAMTS13 activity, and inflammation in diabetic patients on chronic hemodialysis (HD). Blood samples from 52 diabetic patients on chronic HD were obtained to determine vitD levels, vWF, and ADAMTS13 activity, and inflammatory markers. HD patients were grouped according to 25-hydroxyvitamin D [25(OH) VitD]<25 nmol/L (n=16) or >25 nmol/L (n=36). vWF antigen and vWF activity were elevated in both groups, with an average of 214.3±82.6% and 175.8±72.6%, respectively. Average ADAMTS13 activity was within the normal range in both groups. Blood samples from the vitD <25 nmol/L group showed a positive correlation between c-reactive protein (CRP) and vWF levels (P=0.023; r=0.564; 95% confidence interval=0.095-0.828), with a negative correlation between HbA1c and 25(OH) VitD (P=0.015; r=-0.337; 95% confidence interval=-0.337-0.19). Diabetic patients on chronic HD had elevated vWF levels and activity with no significant change in ADAMTS13 activity. The correlation between CRP and vWF levels in the 25(OH) VitD<25 nmol/L group suggests inflammatory-related endothelial dysfunction in these patients.

Keyword

von Willebrand factor; ADAMTS13; Hemodialysis; Diabetes; Vitamin D; Inflammation

MeSH Terms

ADAMTS13 Protein/*metabolism
Aged
C-Reactive Protein/analysis
Diabetes Mellitus, Type 2/complications/*diagnosis/metabolism
Female
Hemoglobin A, Glycosylated/analysis
Humans
Male
Middle Aged
Renal Dialysis
Renal Insufficiency, Chronic/complications/*diagnosis/metabolism
Vitamin D/*analogs & derivatives/blood
von Willebrand Factor/*metabolism
ADAMTS13 Protein
C-Reactive Protein
Hemoglobin A, Glycosylated
Vitamin D
von Willebrand Factor

Figure

  • Fig. 1 Positive correlation between CRP and vWF in hemodialysis patients with 25(OH) VitD <25 nmol/L (P=0.023; r=0.564). Regression line: y=7.52x+175.88Abbreviations: CRP, c- reactive protein; vWF, von Willebrand factor; Ag, antigen.


Reference

1. Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1999; 100:1134–1146. PMID: 10477542.
2. Taniguchi S, Hashiguchi T, Ono T, Takenouchi K, Nakayama K, Kawano T, et al. Association between reduced ADAMTS13 and diabetic nephropathy. Thromb Res. 2010; 125:e310–e316. PMID: 20307901.
3. Domingueti CP, Dusse LM, Fóscolo RB, Reis JS, Annichino-Bizzacchi JM, Orsi FL, et al. Von Willebrand factor, ADAMTS13 and D-Dimer are correlated with different levels of nephropathy in type 1 diabetes mellitus. PLoS One. 2015; 10:e0132784. PMID: 26168189.
4. Lu GY, Shen L, Wang ZY, Guo XF, Bai X, Su J, et al. Significance of plasma von Willebrand factor level and von Willebrand factor-cleaving protease activity in patients with chronic renal diseases. Chin Med J. 2008; 121:133–136. PMID: 18272039.
5. Turner NA, Nolasco L, Ruggeri ZM, Moake JL. Endothelial cell ADAMTS-13 and VWF: production, release, and VWF string cleavage. Blood. 2009; 114:5102–5111. PMID: 19822897.
6. Ford ES, Ajani UA, McGuire LC, Liu S. Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. Diabetes Care. 2005; 28:1228–1230. PMID: 15855599.
7. Holick MF. Vitamin D deficiency. N Engl J Med. 2007; 357:266–281. PMID: 17634462.
8. Cao WJ, Niiya M, Zheng XW, Shang DZ, Zheng XL. Inflammatory cytokines inhibit ADAMTS13 synthesis in hepatic stellate cells and endothelial cells. J Thromb Haemost. 2008; 6:1233–1235. PMID: 18433458.
9. Dugé de Bernonville T, Guyot S, Paulin JP, Gaucher M, Loufrani L, Henrion D, et al. Dihydrochalcones: Implication in resistance to oxidative stress and bioactivities against advanced glycation end-products and vasoconstriction. Phytochemistry. 2010; 71:443–452. PMID: 20022617.
10. Rios DR, Carvalho MG, Figueiredo RC, Ferreira CN, Rodrigues VL, Souza RA, et al. ADAMTS13 and Von Willebrand factor in patients undergoing hemodialysis. J Thromb Thrombolysis. 2012; 34:73–78. PMID: 22298244.
11. Kessler L, Wiesel ML, Attali P, Mossard JM, Cazenave JP, Pinget M. Von Willebrand factor in diabetic angiopathy. Diabetes Metab. 1998; 24:327–336. PMID: 9805643.
12. Dubin R, Cushman M, Folsom AR, Fried LF, Palmas W, Peralta CA, et al. Kidney function and multiple hemostatic markers: cross sectional associations in the multi-ethnic study of atherosclerosis. BMC Nephrol. 2011; 12:3. PMID: 21269477.
13. Taslipinar A, Yaman H, Yilmaz MI, Demirbas S, Saglam M, Taslipinar MY, et al. The relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy. Scand J Clin Lab Invest. 2011; 71:606–612. PMID: 21864054.
14. Reidy K, Kang HM, Hostetter T, Susztak K. Molecular mechanisms of diabetic kidney disease. J Clin Invest. 2014; 124:2333–2340. PMID: 24892707.
15. Rios DR, Fernandes AP, Figueiredo RC, Guimarães DA, Ferreira CN, Simões E, et al. Relationship between ABO blood groups and von Willebrand factor, ADAMTS13 and factor VIII in patients undergoing hemodialysis. J Thromb Thrombolysis. 2012; 33:416–421. PMID: 22466813.
16. Holden RM, Tuttle A, Burbidge T, Hegadorn C, Grabell J, Pruss C, et al. Quantitative and qualitative changes of von Willebrand factor and their impact on mortality in patients with end-stage kidney disease. Blood Coagul Fibrinolysis. 2013; 24:719–726. PMID: 23846000.
17. De Filippis V, Lancellotti S, Maset F, Spolaore B, Pozzi N, Gambaro G, et al. Oxidation of Met1606 in von Willebrand factor is a risk factor for thrombotic and septic complications in chronic renal failure. Biochem J. 2012; 442:423–432. PMID: 22091998.
18. Lancellotti S, De Filippis V, Pozzi N, Peyvandi F, Palla R, Rocca B, et al. Formation of methionine sulfoxide by peroxynitrite at position 1606 of von Willebrand factor inhibits its cleavage by ADAMTS-13: A new prothrombotic mechanism in diseases associated with oxidative stress. Free Radic Biol Med. 2010; 48:446–456. PMID: 19969076.
Full Text Links
  • ALM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr