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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2021  |  Volume : 32  |  Issue : 5  |  Page : 1283-1288
Antithrombin III level in children with nephrotic syndrome, its correlation to thromboembolic complications, and serum albumin level


1 Department of Pediatrics, Faculty of Medicine, Fayoum University, Fayoum, Egypt
2 Department of Medical Physiology, Faculty of Medicine, Fayoum University, Fayoum, Egypt

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Date of Web Publication4-May-2022
 

   Abstract 


Nephrotic syndrome (NS) is one of the most common pediatric diseases with many complications. Thromboembolic complication is the most serious complication. The aim of this study was to predict the possible risk of thromboembolic complication development in children with NS due to antithrombin III deficiency. This study was conducted in the Outpatient Nephrology Clinic of Children’s Hospital in Fayoum University Hospital. It included 27 children with NS and 27 healthy children as a control group in an analytic study with cross-sectional comparative design. Laboratory investigations were done in the form of complete blood picture, serum levels of albumin, total protein, creatinine, urea, cholesterol, triglycerides, urine analysis, albumin/creatinine ratio, prothrombin time, and INR. The serum antithrombin III level was measured by double ELISA technique. Data analysis was performed using the Statistical Package for the Social Sciences software version 18. Student’s t-test was used to compare measures of two independent groups of quantitative data. One-way ANOVA test was used to compare more than two independent groups of quantitative data. Kruskal–Wallis test was used in comparing more than two independent nonparametric groups. Bivariate Pearson correlation test was used to test the association between variables. The level P ≤0.05 was considered significant. There were significant decreases in antithrombin III, albumin, and total protein levels in the study group during relapse and improved after steroid. There were no thromboembolic complications detected among the study group. NS causes heavy proteinuria with loss of many important proteins as antithrombin III. Serum antithrombin III level is significantly decreased in children with NS, and it correlated with serum albumin. Although patients in the study have thrombocytosis, hypercholesterolemia, and decreased serum level of antithrombin III, none of the children in the the study showed thrombotic complication, so we conclude that, thromboembolism is uncommon in children with NS may be due to early diagnosis and proper treatment.

How to cite this article:
Hussein SK, Mohammed AH, Mohammed RA, Abdelghafar H. Antithrombin III level in children with nephrotic syndrome, its correlation to thromboembolic complications, and serum albumin level. Saudi J Kidney Dis Transpl 2021;32:1283-8

How to cite this URL:
Hussein SK, Mohammed AH, Mohammed RA, Abdelghafar H. Antithrombin III level in children with nephrotic syndrome, its correlation to thromboembolic complications, and serum albumin level. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 May 25];32:1283-8. Available from: https://www.sjkdt.org/text.asp?2021/32/5/1283/344747



   Introduction Top


Childhood nephrotic syndrome (NS) is one of the most common pediatric kidney diseases.[1] It is characterized by a triad of proteinuria, edema, and hypoalbuminemia.[2] In a healthy individual, <0.1% of plasma albumin may traverse the glomerular filtration barrier.[3] The glomerular capillaries are covered by glomerular epithelium, or podocytes, which envelops the capillaries with cellular extensions called foot processes. In between the foot processes, there are the filtration slits.[4] The glomerular structural changes that may cause proteinuria are damage to the endothelial surface, the glomerular basement membrane, or the podocytes.[5] Nephrotic-range proteinuria is the loss of 3 g or more per day of protein into the urine or on a single spot urine collection.[4] NS can be associated with a series of complications that can affect an individual’s health and quality of life as thromboembolic disorders.[6] Thromboembolism is considered the most significant life-threatening complication of NS. Children (2.8%) are less likely than adults (26.7%) with NS to develop thromboembolism.[7] Thromboembolic complication in NS is multifactorial. The predisposing factors for thrombosis include venous depletion, hyperlipidemia, thrombocytosis and loss of many hemostatic proteins in the urine.[7] Antithrombin III is a naturally occurring inhibitor of blood coagulation. It inactivates thrombin as well as certain coagulation factors (VIIa, IXa, Xa, and XIa). Low AT III plasma level may lead to potential thrombosis.[8] This study was conducted to detect the serum level of antithrombin III in patients with NS and its correlation to thromboembolic complication.


   Subjects and Methods Top


This cross-sectional study composed of two groups (study group and control group). The study group included 27 children diagnosed with relapsing NS (15 males and 12 females with a male:female ratio: 1.25:1). Patients were recruited from regular attendants of the Pediatric Nephrology Clinic, Fayoum University Hospital, during the period from May to December 2017. Twenty-seven age- and sex-matched healthy subjects were enrolled as a control group. Informed consent was obtained from the guardian of each patient and control before participation. This study was reviewed by the Faculty of Medicine Research Ethical Committee. All children in the study were subjected to complete thorough history taking and physical examination. Laboratory investigations were done in the form of complete blood picture, serum levels of albumin, total protein, creatinine, urea, cholesterol, triglycerides, urine analysis, albumin/creatinine ratio, prothrombin time (PT), and INR. Serum antithrombin III level with double-sandwich ELISA technique, using commercially available kit (MyBioSource, USA Cat#MBS268161), was done. Pelvi-abdominal ultrasound was done for children to exclude renal vein thrombosis and ascites. Investigations were repeated to children with NS after six weeks of the start of steroid therapy.


   Results Top


This cross-sectional study included 27 patients as the study group, recruited from attendants of the pediatric nephrology clinic, and 27 age- and sex-matched healthy subjects as a control group. The mean age of the study group was 5.78 years, with a range between three and 10 years. Males constituted 55.6% of the group, while males constituted 44.4%.

Laboratory results showed a statistically significant decrease in serum albumin, total protein, and antithrombin III values in the study group compared with the control group, while there was a statistically significant increase in serum cholesterol, triglycerides, platelet count, and albumin/creatinine ratio in the study group in relation with the control group [Table 1].
Table 1: Comparison in laboratory results between control group and study group at the start of the study.

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Laboratory results after six weeks of steroid therapy showed improvement of serum albumin, total protein, and antithrombin III levels of the study group but still lower than that of the control group [Table 2]. Furthermore, there was a decrease in serum cholesterol and triglyceride levels in the study group but still higher than that of the control group.
Table 2: Comparison between results of samples collected from control group and study group after 6 weeks of steroid therapy.

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The study group revealed that only five children had simple infections in the form of three cases of gastroenteritis and two cases of bronchitis [Table 3].
Table 3: Incidence of thromboembolic complication and infection in the study group.

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There was no significant relation between age and gender of the patient and the presence of complication [Table 4].
Table 4: Relation between age and gender of patients with complication among the study group.

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There was no significant relation between the number of relapses of the patient and the presence of complication [Table 5].
Table 5: Relation between frequencies of relapse with presence of complication.

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There was a significant positive correlation between the level of antithrombin III and serum albumin, total protein levels, and A/C ratios [Table 6].
Table 6: Correlation between antithrombin III levels in study group with other samples.

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   Discussion Top


Thromboembolism is a well-known but rare complication of pediatric NS. There are variable pathologic alterations of molecular hemostasis associated with NS.[9] Here, we focus on identifying risk for thrombosis through measurement of antithrombin III level in the blood. In the current study, we found that mean serum albumin level and total proteins were significantly decreased during relapse in the study group in relation to the control group due to heavy proteinuria. Six weeks after steroid therapy, albumin level and total proteins were improved in the study group. Similarly, Downie et al. found that patients with NS have hypoalbuminemia.[10] We found a significant decrease in serum antithrombin III level in the study group (nephrotic children) compared to the control group due to heavy proteinuria. Six weeks after steroid therapy, serum antithrombin III level was improved. This was concordant with Lu et al, who found that the mean antithrombin III level of the study group was significantly lower than the level of the control group, and it increased after corticosteroid treatment.[11] We also found, significant increase in serum cholesterol and serum triglyceride levels compared to control group during relapse. Six weeks after steroid therapy, the mean serum cholesterol and serum triglyceride levels dropped but still slightly higher than that of the control group. The decrease in serum cholesterol and triglycerides in the patient was due to increased synthesis of lipoproteins that accompany increased hepatic albumin synthesis Similarly, Dnyanesh et al, in their study that was conducted on 30 children with NS and 10 healthy children as a control group, found that the mean serum cholesterol and triglyceride levels in the study group were elevated in relation to the control group. However, in contrast, they found that after four weeks of steroid therapy, there was no significant change in the mean serum cholesterol or triglyceride levels.[12] As regards platelet count, in our study, we found that during relapse, the mean platelet count was significantly higher than that of the control group and this was a risk factor for developing thrombosis. This was concordant with Gulleroglu et al’s study that was conducted on 55 children with NS as a study group and 29 healthy children as a control group. They found that the mean platelet count in the patient group (403,112 ± 185,605/μL) was significantly higher than that of the control group (326,896 ± 68,765/μL).[13] The pathogenesis of thrombocytosis seems to be multifactorial due to long use of steroid therapy, increased platelet count, decreased antithrombin III and hypercholesterolemia but the exact cause is unknown. In our study, there was no significance between the study group and the control group regarding the bleeding profile. Similarly, Mittal et al’s study that was conducted on 29 children with the steroid-responsive NS found that there was no statistical significance regarding PT before (PT1) and after the steroid therapy (PT2).[14] In our study regarding infection, there were no serious infections among the study group, only five cases (18.5%); three of them had gastroenteritis and the other two cases had bronchitis during relapse. In contrast to our results, Wei et al’s study that was conducted over 176 children found that 19% of the study group was associated with major infections. Pneumonia was the most common infection (49%), followed by urinary tract infection (UTI), bacteremia/sepsis, peritonitis, and cellulitis.[15] In our study, we found that there was a positive correlation between anti-thrombin III level and albumin and subsequent total protein levels, and there was a negative correlation between antithrombin III level and A/C ratio due to increased renal loss of low molecular weight proteins leading to lower their levels in blood and increased protein level in urine. Furthermore, we found that there was a negative correlation between antithrombin III level and cholesterol level that may be due to hypoproteinemia that activates liver lipoprotein synthesis. Similarly, Gyamlani et al’s study found a positive correlation between serum albumin level and the thromboembolic manifestation.[8],[16] Thromboembolism is multifactorial in NS. Although patients in the study have thrombocytosis, hypercholesterolemia, and decreased serum level of antithrombin III, none of the patient showed thrombotic complication, so we conclude that, thromboembolism is not so common in children with NS. This may be due to early diagnosis and proper treatment. Hypoalbuminemia is positively correlated with anti-thrombin III.


   Acknowledgment Top


The authors would like to thank the Faculty of Medicine of Fayoum University.

Conflict of interest: None declared.



 
   References Top

1.
McCloskey O, Maxwell AP. Diagnosis and management of nephrotic syndrome. Practitioner 2017;261:11-5.  Back to cited text no. 1
    
2.
Park SJ, Shin JI. Complications of neph-rotic syndrome. Korean J Pediatr 2012;55:151.  Back to cited text no. 2
    
3.
Noone DG, Iijima K, Parekh R. Idiopathic nephrotic syndrome in children. Lancet 2018; 392:61-74.  Back to cited text no. 3
    
4.
McCampbell KK, Wingert RA. Renal stem cells: Fact or science fiction? Biochem J 2012;444:153-68.  Back to cited text no. 4
    
5.
Caridi G, Trivelli A, Sanna-Cherchi S, Perfumo F, Ghiggeri GM. Familial forms of nephrotic syndrome. Pediatr Nephrol 2010;25: 241-52.  Back to cited text no. 5
    
6.
Bhatt GC, Jain S, Das RR. Zinc supplementation as an adjunct to standard therapy in childhood nephrotic syndrome – A systematic review. World J Clin Pediatr 2016;5:383-90.  Back to cited text no. 6
    
7.
Kerlin BA, Ayoob R, Smoyer WE. Epidemiology and pathophysiology of nephrotic syndrome-associated thromboembolic disease. Clin J Am Soc Nephrol 2012;7:513-20.  Back to cited text no. 7
    
8.
Khor B, Van Cott EM. Laboratory tests for antithrombin deficiency. Am J Hematol 2010; 85:947-50.  Back to cited text no. 8
    
9.
Suri D, Ahluwalia J, Saxena AK, et al. Thromboembolic complications in childhood nephrotic syndrome: A clinical profile. Clin Exp Nephrol 2014;18:803-13.  Back to cited text no. 9
    
10.
Downie ML, Gallibois C, Parekh RS, Noone DG. Nephrotic syndrome in infants and children: Pathophysiology and management. Paediatr Int Child Health 2017;37:248-58.  Back to cited text no. 10
    
11.
Lu Z, Wang F, Liang M. SerpinC1/ Antithrombin III in kidney-related diseases. Clin Sci (Lond) 2017;131:823-31.  Back to cited text no. 11
    
12.
Dnyanesh DK, Dnyanesh S, Shenoy V. A study of serum lipids in nephrotic syndrome in children. J Dent Med Sci 2014;3:1-6.  Back to cited text no. 12
    
13.
Gulleroglu K, Yazar B, Sakalli H, Ozdemir H, Baskin E. Clinical importance of mean platelet volume in children with nephrotic syndrome. Ren Fail 2014;36:663-5.  Back to cited text no. 13
    
14.
Mittal A, Aggarwal KC, Saluja S, Aggarwal A, Sureka B. Platelet functions and coagulation changes in Indian children with nephrotic syndrome. J Clin Diagn Res 2013;7:1647-50.  Back to cited text no. 14
    
15.
Wei CC, Yu IW, Lin HW, Tsai AC. Occurrence of infection among children with nephrotic syndrome during hospitalizations. Nephrology (Carlton) 2012;17:681-8.  Back to cited text no. 15
    
16.
Gyamlani G, Molnar MZ, Lu JL, Sumida K, Kalantar-Zadeh K, Kovesdy CP. Association of serum albumin level and venous thromboembolic events in a large cohort of patients with nephrotic syndrome. Nephrol Dial Transplant 2017;32:157-64.  Back to cited text no. 16
    

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Correspondence Address:
Rehab Ahmed Mohammed
Department of Medical Physiology, Faculty of Medicine, Fayoum University, Fayoum
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.344747

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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    Abstract
   Introduction
   Subjects and Methods
   Results
   Discussion
   Acknowledgment
    References
    Article Tables
 

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