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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 1  |  Page : 340-344

Effect of high-dose omega-3 on inflammatory markers in children on long-term hemodialysis


1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Pediatric, Fever Hospital, Meet Khalaf, Shebin El-Kom, Menoufia Governorate, Menoufia, Egypt

Date of Submission26-Sep-2017
Date of Acceptance03-Dec-2017
Date of Web Publication17-Apr-2019

Correspondence Address:
Alaa M Mohamed K Bassiouny
Shebin El-Kom, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_665_17

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  Abstract 


Objective
The aim of this study was to evaluate the effect of high-dose omega-3 on inflammatory markers in children on long-term hemodialysis.
Background
Children with end-stage renal disease (ESRD) on hemodialysis have elevated serum levels of inflammatory markers. Prevention and treatment of inflammatory syndrome is of high priority in patients who are on hemodialysis. Omega-3 fatty acids have been postulated to reduce inflammatory markers.
Patients and methods
This prospective study included 26 children with ESRD on long-term hemodialysis in the Pediatric Hemodialysis Unit at Menoufia University Hospital who received 2 g omega-3 per day orally for 3 months, and inflammatory markers were assessed and compared before and after omega-3 supplementation.
Results
A total of 26 children were included in the study, and their mean age was 13.4 years (range: 8–17 years). The number of males was 13 (50%), and the number of females was 13 (50%). The comparison of the studied variables before and after supplementation with omega-3 fatty acids showed that there was a highly statistically significant difference between the level of interlukin-6 (IL-6) and C-reactive protein (CRP) before and after omega-3 supplementation. IL-6 level was 149.45 ± 13.477 mg/dl before supplementation, which decreased to 96.19 ± 7.299 mg/dl after supplementation of omega-3 (P < 0.001). CRP level was 10.54 ± 0.884 mg/dl before supplementation, which decreased to 6.499 ± 1.113 mg/dl after supplementation of omega-3 (P < 0.001).
Conclusion
The use of omega-3 fatty acids (2 g/day) caused significant decrease in serum levels of inflammatory markers (IL-6 and CRP) in children with ESRD on long-term hemodialysis.

Keywords: children, chronic kidney disease, hemodialysis, inflammatory markers, omega-3


How to cite this article:
Elshafie AM, Omar ZA, Montser BA, Mohamed K Bassiouny AM. Effect of high-dose omega-3 on inflammatory markers in children on long-term hemodialysis. Menoufia Med J 2019;32:340-4

How to cite this URL:
Elshafie AM, Omar ZA, Montser BA, Mohamed K Bassiouny AM. Effect of high-dose omega-3 on inflammatory markers in children on long-term hemodialysis. Menoufia Med J [serial online] 2019 [cited 2019 Aug 23];32:340-4. Available from: http://www.mmj.eg.net/text.asp?2019/32/1/340/256138




  Introduction Top


Chronic kidney disease (CKD) is the new term defined by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative group to classify any patient who has structural or functional abnormalities of the kidney lasting for at least 3 months with or without a decreased glomerular filtration rate (GFR) or any patient who has a GFR of less than 60 ml/min/1.73 m 2 lasting for 3 months with or without kidney damage [1]. Between 30 and 50% of prevalent patients who are on hemodialysis have elevated serum levels of inflammatory markers. Hemodialyzied patients with inflammation have a poorer prognosis. The prevention and the treatment of inflammatory syndrome are of high priority in patients who are on hemodialysis (HD) [2]. Supplementation with omega-3 polyunsaturated fatty acids has several benefits for reducing inflammation, decreasing oxidative stress, inhibiting platelet activity, and exerting antiarrhythmic effects in patients with CKD [3].

Omega-3 fatty acids have shown promise in modifying a host of disease processes involving the inflammatory pathways, arteriosclerosis, and cardiovascular diseases [4]. Many studies were done in adults with chronic renal failure (CRF) on hemodialysis to assess the effect of omega-3 supplementation on inflammatory markers; however, very little was published about its effect in children.


  Patients and Methods Top


This prospective study was done at the Pediatric Hemodialysis Unit in Menoufia University Hospital and included 26 children with end-stage renal disease (ESRD) on long-term hemodialysis from January 2016 to April 2016. After approval of the local institutional ethical committee of Menoufia University Hospital and obtaining a written consent from all patients who participated in our study, all patients were daily treated orally with 2000 mg Omega-3 plus (SEDICO, South Egypt) containing 360 mg eicosapentaenoic acid and 240 mg docosahexaenoic acid, for 3 months. All children were dialyzed on Fresenius 4008B dialysis machine (Homburg, Germany) using polysuphane hollow fiber dialyzer suitable for the surface area of the patients, and bicarbonate dialysis solutions were used.

All the patients were chosen based on the following inclusion criteria: ESRD with a GFR less than 10 ml/min/1.73 m 2, childhood onset of hemodialysis, age less than 18 years, regular hemodialysis at least three sessions a week, and duration of hemodialysis of more than 3 months.

Exclusion criteria

The exclusion criteria included predialysis stages of CKD, patients on long-term peritoneal dialysis, and patients on regular hemodialysis less than 3 months.

All children underwent the following investigations before and after high-dose omega-3 supplementation: predialysis and postdialysis blood urea nitrogen (BUN); predialysis and postdialysis serum creatinine; predialysis serum total calcium, phosphorous, sodium, potassium, iron, iron-binding capacity, ferritin, and transferrin saturation (measured by standard methods on multichannel AutoAnalyzer; Hitachi, Japan); complete blood count to detect hemoglobin (Hb) and platelet (measured by automated hematology counter on pentra 80; Horiba ABX, France); parathyroid hormone (measured by Mini Vidas, Chemiluminescence; S.A., Lyon, France); interlukin-6 (IL-6) using enzyme-linked immunosorbent assay (ELISA) kit (Invitrogen Corporation, California, USA); and C-reactive protein (CRP) using ELISA kit (Invitrogen Corporation). All these laboratory investigations were done in Clinical Pathology Department, Menoufiya University Hospital.

Sampling

Before dialysis, 6 ml of venous blood was obtained from each patient during the insertion of the A-V fistula needles (in cases of A-V fistulae) or from the venous line of central venous pressure (in cases of central venous pressure) and divided as follows: 2 ml blood of was put in a tube containing EDTA as anticoagulant for performing complete hemogram; 2 ml of blood was left to clot to obtain their serum for performing predialysis BUN, serum creatinine, total calcium, phosphorus, sodium, and potassium; 1 ml was used for IL-6 using ELISA kit (Invitrogen Corporation); and 1 ml was used for CRP using ELISA kit (Invitrogen Corporation). After dialysis, 2 ml of venous blood was obtained from each patient and left to clot to obtain serum for performing postdialysis BUN and serum creatinine measurements.

Statistical analysis

The results were expressed as mean and SD. The collected data were analyzed by statistical package for the social sciences, a program for statistical analysis (SPSS, version 20; SPSS Inc., Chicago, Illinois, USA), using a paired t-test or the Wilcoxon signed-rank test. P values less than 0.001 were considered statistically significant. P values more than 0.05 were considered statistically non-significant.


  Results Top


A total of 26 children participated in this study. Their age ranged from 8 to 17 years old, with a mean age of 13.4 ± 2.5 years. There was an equal number of males and females, with 13 (50%) each. The mean height of the study participants was 129 ± 24.5 cm. Overall, 17 (65.5%) patients had height less than −3 SD on Z score (severely stunted), three (11.5%) patients had height between −2 SD and −3 SD on Z score (stunted), six (23%) patients had height between − 2 SD and 2 SD on Z score (normal), and no patients had height more than 2 SD on Z score. Mean BMI was 17.1 ± 3.2 kg/m 2; four (15.5%) patients had BMI less than −3 SD on Z score (severely wasted), six (23%) patients had BMI between −2 SD and −3 SD on Z score (wasted), 16 (61.5%) patients had BMI between − 2 SD and 2 SD on Z score (normal), and no patients had BMI more than 2 SD on Z score [Table 1].
Table 1: Demographic data and anthropometric measures of the studied patients

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Diseases that led to renal failure are shown in [Table 2]. It shows that the most common cause was obstructive uropathy in 10 (38.4%) patients, glomerulonephritis in five (19.2%) patients, cystic kidney diseases in two (7.7%) patients, cystinosis in one (3.8%) patient, and unknown etiology in eight (30.7%) patients.
Table 2: Etiologies of renal failure of the studied patients

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Supplementation with high-dose omega-3 fatty acids (2 g/day) for 3 months in this study showed that there were no statistically significant differences between the blood pressure (BP), Hb, platelets, total iron-binding capacity, serum iron, transferrin saturation, serum ferritin, parathyroid hormone level, albumin, efficiency of dialysis, and phosphate, calcium, potassium, and sodium levels in the studied patients before and after supplementation of omega-3 [Table 3]. On the contrary, there was a statistically significant decrease in IL-6 and CRP in the studied patients before and after supplementation of omega-3 (P < 0.001) [Table 4].
Table 3: Iron profile, mean hemoglobin, platelets, parathyroid, albumin, efficiency of dialysis, PO4, Ca, K, Na, and blood pressure measurements before and after omega-3 supplementation in the studied patients

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Table 4: Interlukin-6 and C-reactive protein before and after omega-3 supplementation in the studied patients

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  Discussion Top


In our study, the age of the 26 children on long-term hemodialysis ranged from 8 to 17 years old, and their mean age was 13.4 ± 2.5 years. The mean height and BMI SD on Z score were 129 ± 24.5 cm and 17.1 ± 3.2 kg/m 2, respectively. Similar to our results, Ghobrial et al. [5] found that 78% of 50 children with ESRD on regular hemodialysis were growth retarded. Moreover, Pundziene et al. [6] showed that 30.9% children with GFR of less than 60 ml/min/1.73 m 2 and 43.7% with ESRD were also growth retarded. This agreed with our study, because growth retardation is one of the most common and profound clinical manifestation of CKD in infants and children on hemodialysis. This may be because of poor nutrition, metabolic acidosis, osteodystrophy, and anemia. Hari et al. [7] recorded that, of 305 children, the mean age at presentation of CRF in the patients was 8 years. In the study done by Al-Harthi [8] on 99 patients, the mean age at diagnosis was 8.68 ± 6.3 years. The observed variation in the mean age of presentation from our patients may be because of screening, early detection of cases, and regular follow-up.

In this current study, the number of males was 13 (50%) and the number of females was 13 (50%). However, a study by Rahman et al. [9] noted that among 44 children with CRF, 30 (68.19%) cases were males and 14 (31.81%) cases were females. This may be because of a predominance of males with renal dysplasia and obstructive uropathy causing CRF, which can explain the variation of sex compared with our study. The equality of sex in our study may be because of a small sample size.

In our study, we found that the most common etiologies of renal failure were obstructive uropathy and unknown etiology in 10 (38.4%) patients and eight (30.7%) patients, respectively. Al Eisa et al. [10] in their study in Kuwait on children aged 0–15 years with a GFR less than 50 ml/min/1.73 m 2 agreed with our result that obstructive uropathy is the most common cause of renal failure, with a percentage of 29.2%. However, they found that unknown etiology is responsible for 1.7% of all causes of renal failure, which disagree with our results. This disagreement may be because of small sample size in our study or late health care seeking by patients or lack of diagnostic facilities in developing countries which make diagnosis of the etiology of renal failure more difficult and raise the unknown etiology percentage.

Supplementation of high-dose omega-3 (2 g/day) orally for 3 months in this study showed that there was no statistically significant difference in the levels of BP before and after supplementation (P > 0.05). On the contrary, Afsoon et al. [11] recorded that in 170 patients with ESRD on regular dialysis who were 18 years old or more and received 3 g/day omega-3 for 8 weeks, BP was significantly reduced. This finding may be because of the use of very high dose of omega-3 (3 g/day). Moreover, Omrani et al. [12] agreed with our results that omega-3 supplementation did not significantly affect the BP in their randomized clinical trial on 60 hemodialysis adult patients. The experimental group took 1000 mg daily omega-3 capsules for 10 weeks; this may be because of low dose of omega-3 (1 g/day). In our study, there was no statistically significant difference in the levels of anemia and iron profile before and after supplementation with omega-3 fatty acids (P > 0.05). In relation to this, Afshin et al. [13] reported no significant changes in blood Hb and serum iron in 54 adults with ESRD on HD duration of at least 3 months who were randomized to ingest 1800 mg of either omega-3 fatty acids or matching placebo per day for 4 months.

Daily consumption of 2 g of omega-3 fatty acid for 3 months in our study significantly reduced inflammatory markers (IL-6 and hs-CRP). The study done by Jalil et al. [14] found that the use of omega-3, 3 g per day, was well tolerated and had a positive effect in reduction of inflammation markers hs-CRP and IL-6. This was also in agreement with studies carried out by Dashti et al. [13] that demonstrated that ingestion of 1800 mg of omega-3 fatty acids per day for 4 months relatively improved hs-CRP and IL-6 of chronic hemodialyzed patients. Moreover, the results of the effect of high-dose omega-3 supplementation (2.4 g/day) showed beneficial effects on CRP levels after their routine dialysis session for 6 months in the study done byAdams et al. [15]. However, the study done by Elshafie et al. [16] showed that there was no significant difference in hs-CRP levels when 23 children with CRF on regular hemodialysis were daily treated with 1000 mg omega-3 plus for 3 months. Moreover, the study by Bowden et al. [17] demonstrated that consuming 960 mg/day of eicosapentaenoic acid and 600 mg/day of docosahexaenoic acid can lower CRP levels. However, low-dose omega-3 fatty acids had no effect on the plasma hs-CRP levels. This disagreement may be because of low dose of omega-3.

In summary, Fiedler et al. [18] concluded that only high doses of omega-3 fatty acids given for a longer time would influence inflammation. Therefore, significant reduction in hs-CRP and IL-6 in our study may be because of administration of high dose of omega-3 and longer duration of omega-3 supplementation to exerts its anti-inflammatory effect.


  Conclusion Top


Supplementation of high-dose omega-3 fatty acids (2 g/day) led to significant decrease in serum levels of IL-6 and CRP in children on chronic hemodialysis, and its use may be recommended in such patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Afsoon EN, Nooshin K, Mojgan M, Taheri S, Hassien SM. Effect of omega-3 fatty acids on blood pressure and serum lipids in continuous ambulatory peritoneal dialysis patients. J Res Pharm Pract 2015; 4:135–141.  Back to cited text no. 11
    
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Omrani H, Pasdar Y, Raisi D, Najafi F, Esfandiari A. The effect of omega-3 on serum lipid profile in hemodialysis patients. J Renal Inj Prev 2015; 4:68–72.  Back to cited text no. 12
    
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    Tables

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



 

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