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ORIGINAL ARTICLE
Adv Biomed Res 2016,  5:118

Association of E-selectin with hematological, hormonal levels and plasma proteins in children with end stage renal disease


1 Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan; Department of Medical Sciences, Najafabad Branch, Islamic Azad University, Isfahan, Iran
2 Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
3 Isfahan Center of Health Research, Isfahan University of Medical Sciences, Isfahan; National Institute of Health Research, Tehran University of Medical Sciences, Tehran, Iran
4 National Institute of Health Research, Tehran University of Medical Sciences, Tehran, Iran

Date of Submission03-Feb-2014
Date of Acceptance01-Nov-2014
Date of Web Publication29-Jul-2016

Correspondence Address:
Dr. Alaleh Gheissari
Department of Pediatric Nephrology, Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan
Iran
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Source of Support: This work was founded by Grant no. 291173 from Isfahan Kidney Diseases Research Center, Isfahan University of Medical sciences, Isfahan, Iran,, Conflict of Interest: None


DOI: 10.4103/2277-9175.186992

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  Abstract 

Background: Hypercoagulable state is a common serious problem in patients with end-stage renal disease (ESRD). ESRD patients are in a condition of chronic inflammation. An increased level of E-selectin, “a key adhesion molecule that regulates leukocyte bindings to endothelium at damaged sites,” accompanies the higher risk of inflammation in ESRD patients. We aimed to investigate the possible correlation among E-selectin as an adhesion molecule, coagulation factors, and inflammatory factors in children with ESRD.
Materials and Methods: Thirty-five child patients with ESRD who had been on regular dialysis treatment were registered in our study. Nighteen sex- and age-matched healthy volunteers were used as the control group. Laboratory tests were requested for the evaluation of hematological and biochemical parameters, and parathyroid hormone (PTH), and for coagulation state; fibrinogen, protein C, and protein S were measured. The enzyme-linked immunosorbent assay (ELISA) (Biomerica, CA, and IDS, UK). for serum E-selectin assay was provided by R and D Systems (Abingdon, UK).
Results: Hemoglubolin (Hb), blood urea nitrogen (BUN), creatinine, calcium, PTH, triglyceride (TG) concentrations in serum as well as E-selectin showed significant difference between the two study groups, as indeed was expected. Serum E-selectin was significantly higher (P value = 0.033) in dialysis patients than in healthy subjects. E-selectin was positively correlated only with phosphorus in ESRD children (r = 0.398,P = 0.018). No association was found for other parameters.
Conclusion: Although in our study circulating E-selectin concentration “as an inflammatory maker” is independently positively associated with limited blood markers, for better evaluation, well-designed cohort studies should be examined in ESRD children.

Keywords: E-selectin, hematological and hormonal levels, plasma proteins, renal disease


How to cite this article:
Meamar R, Shafiei M, Abedini A, Ghazvini MR, Roomizadeh P, Taheri S, Gheissari A. Association of E-selectin with hematological, hormonal levels and plasma proteins in children with end stage renal disease. Adv Biomed Res 2016;5:118

How to cite this URL:
Meamar R, Shafiei M, Abedini A, Ghazvini MR, Roomizadeh P, Taheri S, Gheissari A. Association of E-selectin with hematological, hormonal levels and plasma proteins in children with end stage renal disease. Adv Biomed Res [serial online] 2016 [cited 2020 Oct 19];5:118. Available from: https://www.advbiores.net/text.asp?2016/5/1/118/186992


  Introduction Top


Hypercoagulable state is a common serious problem in patients with end-stage renal disease (ESRD). ESRD patients are in a state of chronic inflammation. Inflammation in conjunction with hypercoagulability increases mortality and CV morbidity in dialysis patients.[1],[2] Various factors have been investigated as the possible causes of inflammation. Among these factors, pro-inflammatory cytokines, adhesion molecules, homocysteine, and parathyroid hormone-related protein (PTHrP) have been widely discussed.[3],[4],[5],[6] Since adhesion of leukocytes to the impaired endothelium plays a crucial role in the inflammatory process, focusing on different adhesion molecules conveys new evidence. E-selectin, a member of the selectin family is a key adhesion molecule that regulates leukocyte bindings to endothelium at damaged sites.[7],[8] An increased level of E-selectin accompanies the higher risk of inflammation in ESRD patients.[7] In spite of the bulk of studies considering the levels of adhesion molecules in ESRD adults, data on ESRD children is scarce. Therefore, we aimed to investigate the possible correlation among E-selectin as a key adhesion molecule, proteins C and S as markers of anticoagulation state, fibrinogen as a coagulation factor, homocysteine as an independent factor of thrombosis, and parathyroid hormone (PTH) as a known inflammatory factor in ESRD children.


  Materials and Methods Top


Thirty-five child patients with ESRD (13 male and 22 female) who had been on regular dialysis treatment (on hemodialysis [HD] and on peritoneal dialysis [PD]) for at least 6 months were registered in our study. Nineteen sex- and age-matched healthy volunteers were used as the control group. A fasting blood sampling was performed between 8.00 and 10.00 am.

The following laboratory tests were requested for the evaluation of hematological and biochemical parameters: complete blood count (CBC), hemoglobulin (Hb) (g/dl), blood urea nitrogen (BUN) (mg/dl), creatinine (mg/dl), triglyceride (TG) (mg/dl), cholesterol (mg/dl), low density lipoprotein (LDL) (mg/dl), and high density lipoprotein (HDL) (mg/dl). Serum biochemicals were measured with Hitach 902 (Boehringer Mannheim, Germany) autoanalyzer using commercial kits. Hematological parameters were determined by using the Sysmex K1000 (TOA Medical Electronics, Japan). PTH (normal range: 10-65 IU/l) were analyzed by ELISA (Biomerica, CA, and IDS, UK). Other laboratory data from peripheral blood including calcium (mg/dl) and phosphorus (mg/dl) were assessed by spectrophotometric methods Hitach 902 (Boehringer Mannheim, Germany) autoanalyzer). Fibrinogen (mg/dl), Protein C(%) and Protein S (%) were measured by coagulation based assays using Mahsa-yaran (Iran) and Hyphen Biomed (France) products. Serum homocystein(μmol/L) levels were enzymaticallydetermined by using a commercial kit from Axis-shield diagnostics (UK). The ELISA kit for serum E-selectin (ng/ml) assay was provided by R and D Systems (Abingdon, UK).

Statistical analysis

Standard statistical methods (mean ± SD) were utilized to summarize parametric values, and t-test and D'Agostino's K2 test were performed to compare the control group with the case group of children with ESRD. Statistical analysis was conducted by using the SPSS version 18 (IBM, USA). The Pearson correlation analysis was used to examine the correlations between plasma E-selectin and the values of the other parameters.


  Results Top


The mean values for age in the case and control groups were 13.37 ± 4.7 years and 11.14 ± 3.93 years, respectively, P > 0.05. Demographic data of the case group are demonstrated in [Table 1]. [Table 2] shows different variables in patients with ESRD and in the control group. Hb, BUN, creatinine, calcium, PTH, and TG concentrations in serum as well as E-selectin behaved significantly differently in the two study groups, as indeed was expected. Serum E-selectin was significantly higher (P = 0.033) in dialysis patients than in healthy subjects. The correlation analysis for E-selectin and relevant parameters is included in [Table 3]. According to this table E-selectin was positively correlated only with phosphorus in ESRD patients. No association was found for the other parameters.
Table 1: Demographic data of case group

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Table 2: Biometric, biochemical, and hormonal levels in patients with ESRD and controls group

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Table 3: Correlation between plasma E-selectin and relevant parameters in 39 patients with ESRD

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  Discussion Top


In the present study, we evaluated the levels of leukocyte adhesion molecules (E-selectin) and its correlation with some inflammatory and thrombosis factors in ESRD children. To the best of our knowledge, it is the first study that compares such markers in this age group.

In addition to the traditional risk factors of CV morbidity in a normal population, such as hypertension and dyslipidemia, ESRD patients have a higher incidence of thrombosis due to disease-specific risk factors. Among these causes the following factors: hyperparathyroidism (HPT), hyperphosphatemia, anemia, and homocysteinemia have been given more attention.[9] In addition, it has been shown that endothelial dysfunction and inflammation are linked to renal function impairment [10] as well as acting as one of the first hallmarks in the pathogenesis of atherosclerosis.[11]

Adhesion molecules such as E-selectin, P-selectin, and L-selectin provoke leukocyte adhesion and advance a series of events to arterial injury. For a variety of proatherogenic conditions such as type 2 diabetes [12] and salt-sensitive hypertension,[13] increased levels of E-selectin have been described; this is compatible with our observation of a significant elevation of E-selectin in children with ESRD. Actually, high E-selectin in these conditions is currently explained as a marker of endothelium injury.[14] E-selectin, after stimulation by cytokines, is expressed provisionally on endothelial cells only upon damage,[15] therefore, it is reasonable that an elevated E-selectin level in the urine may serve as an early indicator for kidney damage.[16] Indeed, E-selectin was presented as a risk factor in ESRD [6] as the Leu554Phe polymorphism of the E-selectin gene is related with the severity of carotid atherosclerosis in ESRD patients leading to susceptibility to the damaging effects of inflammation on the arterial wall.[17] As regards this marker acting as a risk factor for ESRD, a relationship between E-selectin and different risk factors in ESRD seems logical. The positive correlation between E-selectin and BMI, blood pressure and TG in cases without a past medical history of cardiovascular disease (CVD), diabetes, or stroke has been presented,[18] but E-selectin had a positive association only with serum phosphorus in our reports.

Hyperphosphatemia is a predictable event of progressive chronic renal failure or after renal transplantation and in the majority of ESRD patients on dialysis.[19],[20] Hyperphosphatemia is one of the main risk factors for the progression of secondary HPT, and this condition is correlated with the enhancement of CV morbidity and mortality in ESRD patients.[21] The endothelium was recognized as a target for PTH, and HPT is associated with subclinical inflammation and endothelial dysfunction.[22] In HPT patients, the vasoactivity of endothelium was altered, and such modification may increase the risk of CVDs.[22] Regarding the fact that 97% of patients in our study had HPT; we conclude that HPT can be act as one of the reason for increment of E-selectin.

Another commonly used marker for kidney injury is serum creatinine, and it has been suggested that there is an inverse association between inflammatory molecules and creatinine clearance.[23] Previous studies have also presented that a reduced glomerular filtration rate was accompanied with an increased CV mortality and morbidity.[24] In patients with predialysis renal failure, reduction in endothelium vasodilatation has been shown. The association between creatinine clearance and some biochemical markers of endothelial dysfunction such as sVCAM-1 has been presented,[10] but in our study we did not find any correlation between creatinine and E-selectin; our small sample size could explain this difference.

In summary, the circulating E-selectin concentration is independently positively associated only with serum phosphorus in Iranian children with ESRD, but for better evaluation, well-designed cohort studies should be performed for this population.

 
  References Top

1.
Tripepi G, Mallamaci F, Zoccali C. Inflammation markers, adhesion molecules, and all-cause and cardiovascular mortality in patients with ESRD: Searching for the best risk marker by multivariate modeling. J Am Soc Nephrol 2005;16(Suppl 1):S83-8.  Back to cited text no. 1
    
2.
Zoccali C, Mallamaci F, Tripepi G. Inflammation and atherosclerosis in end-stage renal disease. Blood Purif 2003;21:29-36.  Back to cited text no. 2
    
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Stenvinkel P. Inflammation in end-stage renal failure: Could it be treated? Nephrol Dial Transplant 2002;17(Suppl 8):33-8; discussion 40.  Back to cited text no. 3
    
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Martín-Ventura JL, Ortego M, Esbrit P, Hernández-Presa MA, Ortega L, Egido J. Possible role of parathyroid hormone-related protein as a proinflammatory cytokine in atherosclerosis. Stroke 2003;34:1783-9.  Back to cited text no. 4
    
5.
Bostom AG, Culleton BF. Hyperhomocysteinemia in chronic renal disease. J Am Soc Nephrol 1999;10:891-900.  Back to cited text no. 5
    
6.
Malatino LS, Stancanelli B, Cataliotti A, Bellanuova I, Fatuzzo P, Rapisarda F, et al. Circulating E-selectin as a risk marker in patients with end-stage renal disease. J Intern Med 2007;262:479-87.  Back to cited text no. 6
    
7.
Testa A, Benedetto FA, Spoto B, Pisano A, Tripepi G, Mallamaci F, et al. The E-selectin gene polymorphism and carotid atherosclerosisin end-stage renal disease. Nephrol Dial Transplant 2006;21:1921-6.  Back to cited text no. 7
    
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Springer TA. Adhesion receptors of the immune system. Nature 1990;346:425-34.  Back to cited text no. 8
    
9.
Zoccali C, Mallamaci F, Tripepi G. Traditional and emerging cardiovascular risk factors in end-stage renal disease. Kidney Int Suppl 2003;S105-110.  Back to cited text no. 9
    
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Stam F, van Guldener C, Schalkwijk CG, ter Wee PM, Donker AJ, Stehouwer CD. Impaired renal function is associated with markers of endothelial dysfunction and increased inflammatory activity. Nephrol Dial Transplant 2003;18:892-8.  Back to cited text no. 10
    
11.
Vanhoutte PM. Endothelial dysfunction and atherosclerosis. Eur Heart J 1997;18(Suppl E):E19-29.  Back to cited text no. 11
    
12.
Thorand B, Baumert J, Chambless L, Meisinger C, Kolb H, Döring A, et al.; MONICA/KORA Study Group. Elevated markers of endothelial dysfunction predict type 2 diabetes mellitus in middle-aged men and women from the general population. Arterioscler Thromb Vasc Biol 2006;26:398-405.  Back to cited text no. 12
    
13.
Ferri C, Bellini C, Desideri G, Giuliani E, De Siati L, Cicogna S, et al. Clustering of endothelial markers of vascular damage in human salt-sensitive hypertension: Influence of dietary sodium load and depletion. Hypertension 1998;32:862-8.  Back to cited text no. 13
    
14.
Nasuno A, Matsubara T, Hori T, Higuchi K, Imai S, Nakagawa I, et al. Levels of soluble E-selectin and ICAM-1 in the coronary circulation of patients with stable coronary artery disease: Association with the severity of coronary atherosclerosis. Jpn Heart J 2002;43:93-101.  Back to cited text no. 14
    
15.
Bevilacqua MP, Stengelin S, Gimbrone MA Jr, Seed B. Endothelial leukocyte adhesion molecule 1: An inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 1989;243:1160-5.  Back to cited text no. 15
    
16.
Gearing AJ, Hemingway I, Pigott R, Hughes J, Rees AJ, Cashman SJ. Soluble forms of vascular adhesion molecules, E-selectin, ICAM-1, and VCAM-1: Pathological significance. Ann NY Acad Sci 1992;667:324-31.  Back to cited text no. 16
    
17.
Issac MS, Afif A, Gohar NA, Fayek NA, Zayed B, Sedrak H, et al. Association of E-selectin gene polymorphism and serum PAPP-A with carotid atherosclerosis in end-stage renal disease. Mol Diagn Ther 2014;18:243-52.  Back to cited text no. 17
    
18.
Mochizuki K, Inoue S, Miyauchi R, Misaki Y, Shimada M, Kasezawa N, et al. Plasma sE-selectin level is positively correlated with neutrophil count and diastolic blood pressure in Japanese men. J Nutr Sci Vitaminol (Tokyo) 2013;59:447-53.  Back to cited text no. 18
    
19.
Malberti F. Hyperphosphataemia: Treatment options. Drugs 2013;73:673-88.  Back to cited text no. 19
    
20.
Kumar R, Thompson JR. The regulation of parathyroid hormone secretion and synthesis. J Am Soc Nephrol 2011;22:216-24.  Back to cited text no. 20
    
21.
Voormolen N, Noordzij M, Grootendorst DC, Beetz I, Sijpkens YW, van Manen JG, et al.; PREPARE study group. High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients. Nephrol Dial Transplant 2007;22:2909-16.  Back to cited text no. 21
    
22.
Lumachi F, Zanella S, Cella G, Casonato A, Fallo F. Endothelial activation markers soluble E-selectin and von Willebrand factor in primary hyperparathyroidism.In Vivo 2011;25:279-82.  Back to cited text no. 22
    
23.
Pecoits-Filho R, Heimbürger O, Bárány P, Suliman M, Fehrman-Ekholm I, Lindholm B, et al. Associations between circulating inflammatory markers and residual renal function in CRF patients. Am J Kidney Dis 2003;41:1212-8.  Back to cited text no. 23
    
24.
Garg AX, Clark WF, Haynes RB, House AA. Moderate renal insufficiency and the risk of cardiovascular mortality: Results from the NHANES I. Kidney Int 2002;61:1486-94.  Back to cited text no. 24
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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