Von Willebrand factor, ADAMTS13 activity, TNF-α and their relationships in patients with chronic kidney disease

Shen,Lei; Lu,Guoyuan; Dong,Ningzheng; Jiang,Liqiong; Ma,Zhenni; Ruan,Changgeng

doi:10.3892/etm.2011.432

Von Willebrand factor, ADAMTS13 activity, TNF-α and their relationships in patients with chronic kidney disease

Authors:
- Lei Shen
- Guoyuan Lu
- Ningzheng Dong
- Liqiong Jiang
- Zhenni Ma
- Changgeng Ruan
View Affiliations

Affiliations: Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, Jiangsu 215006, P.R. China
Published online on: December 23, 2011 https://doi.org/10.3892/etm.2011.432
Pages: 530-534

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Patients with chronic kidney disease (CKD) often exhibit associated endothelial dysfunction and inflammation. Systemic inflammation may contribute to the endothelial dysfunction and accelerated thrombosis observed in CKD patients. In this study, we assessed the relationships among endothelial dysfunction, a disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13 (ADAMTS13) activity and levels of inflammatory cytokines in CKD patients. CKD patients were classified into three groups: The chronic glomerulonephritis group (CGN; n=31), the idiopathic nephritic syndrome group (NS; n=32) and the lupus nephritis group (LN; n=41). We measured the plasma levels of tumor necrosis factor-α (TNF-α), von Willebrand factor (VWF) antigen (VWF:Ag) and ADAMTS13 activity using an ELISA-based method in CKD patients (n=104) and normal controls (n=32). The ratio of the VWF:Ag levels to ADAMTS13 activity was calculated. The VWF:Ag levels were significantly higher and the ADAMTS13 activities were significantly lower in the disease groups compared to the controls (P<0.01). ADAMTS13 activity was lower in the NS group compared to the CGN and LN groups (P<0.05). The TNF-α levels were higher in the CKD group compared to the control group (P<0.01). TNF-α was positively correlated with the VWF:Ag levels (r=0.242, P=0.013) and negatively correlated with the glomerular filtration rate (GFR) (r=-0.193, P=0.049). ADAMTS13 activity was negatively correlated with the cholesterol levels in CKD patients (r=-0.2, P=0.042). TNF-α levels in CKD were positively correlated with the VWF:Ag levels and negatively correlated with GFR, which indicates that inflammation may be a major cause of endothelial dysfunction and an index of renal function. The VWF:Ag levels increased and ADAMTS13 activity decreased in CKD patients, which indicates that CKD leads to a prothrombotic state.

View Figures

View References

1.	G OcakM VerduijnCY VossenChronic kidney disease stages 1–3 increase the risk of venous thrombosisJ Thromb Haemost8242824352010
2.	CH BoltonLG DownsJG VictoryJF DwightCR TomsonMI MacknessJH PinkneyEndothelial dysfunction in chronic renal failure: roles of lipoprotein oxidation and pro-inflammatory cytokinesNephrol Dial Transplant1611891197200110.1093/ndt/16.6.118911390719
3.	F Guebre-EgziabherD FouqueMetabolic consequences of inflammation in kidney failureNephrologie24383386200314650751
4.	TV PatelBV MittalSR Keithi-ReddyJS DuffieldAK SinghEndothelial activation markers in anemic non-dialysis chronic kidney disease patientsNephron Clin Pract110c244c250200810.1159/00016787218974656
5.	Y Lopez-AguirreJA ParamoEndothelial cell and hemostatic activation in relation to cytokines in patients with sepsisThromb Res9495101199910.1016/S0049-3848(98)00200-X10230894
6.	GG LevyWC NicholsEC LianMutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpuraNature413488494200110.1038/3509700811586351
7.	TC NguyenA LiuL LiuAcquired ADAMTS-13 deficiency in pediatric patients with severe sepsisHaematologica92121124200710.3324/haematol.1026217229645
8.	AD BlannPlasma von Willebrand factor, thrombosis, and the endothelium: the first 30 yearsThromb Haemost954955200616543961
9.	T OnoJ MimuroS MadoiwaSevere secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failureBlood107528534200610.1182/blood-2005-03-1087
10.	GY LuL ShenZY WangXF GuoX BaiJ SuCG RuanSignificance of plasma von Willebrand factor level and von Willebrand factor-cleaving protease activity in patients with chronic renal diseasesChin Med J121133136200818272039
11.	AO SpielJC GilbertB Jilmavon Willebrand factor in cardiovascular disease: focus on acute coronary syndromesCirculation11714491459200810.1161/CIRCULATIONAHA.107.72282718347221
12.	L UlloaKJ TraceyThe ‘cytokine profile’: a code for sepsisTrends Mol Med1156632005
13.	RS HotchkissIE KarlThe pathophysiology and treatment of sepsisN Engl J Med348138150200310.1056/NEJMra02133312519925
14.	A BernardoC BallL NolascoJF MoakeJF DongEffects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flowBlood104100106200410.1182/blood-2004-01-010715026315
15.	WJ CaoM NiiyaXW ZhengDZ ShangXL ZhengInflammatory cytokines inhibit ADAMTS13 synthesis in hepatic stellate cells and endothelial cellsJ Thromb Haemost612331235200810.1111/j.1538-7836.2008.02989.x18433458
16.	M MatsukawaK KaikitaK SoejimaSerial changes in von Willebrand factor-cleaving protease (ADAMTS13) and prognosis after acute myocardial infarctionAm J Cardiol100758763200710.1016/j.amjcard.2007.03.09517719316
17.	RA ClausCL BockmeyerU BuddeVariations in the ratio between von Willebrand factor and its cleaving protease during systemic inflammation and association with severity and prognosis of organ failureThromb Haemost1012392472009
18.	National Kindney FoundationK/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratificationAm J Kidney Dis39S1S266200211904577
19.	JH BerdenLupus nephritisKidney Int52538558199710.1038/ki.1997.3659264014
20.	C BombardierDD GladmanMB UrowitzD CaronCH ChangDerivation of the SLEDAI. A disease activity index for lupus patients The Committee on Prognosis Studies in SLEArthritis Rheum35630640199210.1002/art.17803506061599520
21.	K KokameY NobeY KokuboA OkayamaT MiyataFRETS-VWF73, a first fluorogenic substrate for ADAMTS13 assayBr J Haematol12993100200510.1111/j.1365-2141.2005.05420.x15801961
22.	GC Del VecchioR PenzaM AltomareCytokine pattern and endothelium damage markers in Henoch-Schonlein purpuraImmunopharmacol Immunotoxicol30623629200818668398
23.	T KobayashiH WadaN NishiokaADAMTS13 related markers and von Willebrand factor in plasma from patients with thrombotic microangiopathy (TMA)Thromb Res121849854200810.1016/j.thromres.2007.08.00317900666
24.	AM SilveiraS SjobergM BlombackJ Ostmanvon Willebrand factor antigen in plasma and urine in patients with type I (insulin-dependent) diabetes mellitus with and without nephropathyJ Diabetes Complications68995199210.1016/1056-8727(92)90017-F
25.	JA Kremer HovingaS ZeerlederP KesslerADAMTS-13, von Willebrand factor and related parameters in severe sepsis and septic shockJ Thromb Haemost522842290200717764538
26.	SK NadarE Al YemeniAD BlannGY LipThrombomodulin, von Willebrand factor and E-selectin as plasma markers of endothelial damage/dysfunction and activation in pregnancy induced hypertensionThromb Res113123128200410.1016/j.thromres.2004.02.010