Patients on hemodialysis (HD) experience elevated oxidative stress because of uremic toxins and oxidative compounds, which surpass the body’s antioxidant defenses. As kidney function declines, OS worsens, especially during the HD process [14].

Omega-3 ingestion could reduce oxidative stress and inflammation [15]. However, most studies focused on adult patients rather than pediatrics [16].

Serum TBARS levels had a positive correlation with the dialysis duration. TBARS is a common indicator of oxidative stress in uremia, effectively measuring malondialdehyde, a lipid peroxidation product linked to cellular injury. Studies indicate that TBARS production increases in the late stages of CKD and hemodialysis patients [17].

We noted a significant decrease in serum TBARS levels in the study group than in the placebo group after 6 months of intervention. Our findings align with Bouzidi et al., who evaluated the effects of poly unsaturated fatty acids (PUFA) supplementation over 3 months in adult patients with CKD [18].

Omega-3 fatty acids may reduce TBARS by incorporating into membrane lipids and lipoproteins, making double bonds less vulnerable to free radical attack. They also inhibit the pro-oxidant phospholipase A2 and stimulate antioxidant enzymes, while up regulating antioxidant gene expression and downregulating genes that produce reactive oxygen species [8].

GSH-Px level had a negative correlation with the dialysis duration in our cohort. Glutathione (GSH) is a key non-enzymatic antioxidant and a stable biomarker for redox imbalance, and its Plasma levels are reduced in chronic kidney disease [19].

Glutathione peroxidase (GSH-Px) levels increased significantly after 6 months in the study group. Heshmati et al., found that taking omega-3 supplementations significantly increased glutathione peroxidase levels [20]. Additionally, Ateya et al., reported a substantial increase in glutathione peroxidase in children who received omega 3 (1 g/day) for 16 weeks [21]. Bouzidi et al., also demonstrated that administering omega-3 to adult patients undergoing hemodialysis raised their glutathione peroxidase levels [18].

Omega-3 has antioxidant and anti-inflammatory effects. It enhances the body’s natural antioxidant defenses, like glutathione, by activating key enzymes like γ-glutamyl-cysteinyl ligase, glutathione reductase, and glutathione S-transferase. Additionally, omega-3 competes with arachidonic acid at COX-2 and xanthine oxidase sites, which helps reduce the formation of reactive oxygen species [22, 23].

Hypertension is a common complication in children undergoing renal replacement therapy. Ilkhamdzhan et al., found that hypertension affects 45–60% of dialysis patients as CKD progresses [24]. Our study results showed a significant positive correlation between serum TBARS and systolic blood pressure. Conversely, GSH-Px levels correlated negatively with both systolic and diastolic blood pressure.

Disturbed nitric oxide (NO) availability significantly contributes to hypertension through endothelial dysfunction, which involves decreased vasorelaxation and activation of endothelial cells. Key mechanisms include (1) increased levels of asymmetric dimethylarginine (ADMA), are linked to vascular disease in CKD patients. (2) Uremic toxins like indoxyl sulfate (IS) and homocysteine elevate NADPH oxidase 4 (NOX4) activity, leading to oxidative stress and further dysfunction. (3) Angiotensin II activates NOX, playing a critical role in arterial hypertension [25].

We found a significant positive correlation between serum GSH-Px levels and height Z-scores in the study group. Conversely, a significant inverse correlation was noted between serum TBARS levels and height Z-scores which aligns with the study by Aly et al. [26].

Oxidative stress in malnourished children arises from several factors. The primary cause is the inadequate intake of essential micronutrients causing accumulation of reactive oxygen species (ROS). Additionally, chronic inflammation can cause ongoing immune system activation, further elevating oxidative stress [26].

We found no statistically significant differences between both groups in hemoglobin level. This aligns with Zhang et al., and Omar et al., who found no alterations in hemoglobin levels after 3 months of daily oral omega-3 supplementation using 1 gand 2-g dose respectively [27, 28].

In contrast, Perunicic-Pekovic et al., demonstrated that a higher dose (2.4 g/day) over 8 weeks significantly increased hemoglobin levels [29]. These variable results may be due to the variations in study design, duration and dosage of supplementation, diet, and hemoglobin levels [30].

Increased oxidative stress worsens anemia in hemodialysis patients through lipid peroxidation, which shortens the red blood cells’ life span [31], which may account for the observed negative correlation between serum TBARS and hemoglobin levels in our trial.

There was no significant alteration in serum ferritin and transferrin saturation. This aligns with the findings of Omar et al., and El-Mashad et al. [28, 32]. The lack of improvement in transferrin saturation with omega-3 supplements may be due to lower dosages, favorable baseline levels, or variable iron intake [30].

Serum ferritin is a better indicator of systemic inflammation than iron stores, as evidenced by greater reductions in ferritin levels among patients treated with omega-3 who showed decreased systemic inflammation, and the positive correlation between it and serum TBARS [30].

In our study, albumin levels remained largely unchanged following the intervention. This can be clarified by the fact that serum albumin may not quickly reflect sudden changes in nutrition due to its extended half-life, and it can also decrease due to volume overload and systemic inflammation.

Conversely, Perunicic Pekovic et al., who administered a greater dosage of omega-3, observed a notable rise in serum albumin following the intervention, likely attributed to enhanced appetite [29].

Serum albumin had a significant negative correlation with serum TBARS level and a positive correlation with serum GSH-Px. However, there is no existing data on hypoalbuminemia and oxidative stress in children. Danielski et al., noted that adult hemodialysis patients with ESRD and hypoalbuminemia had higher inflammatory and oxidative stress biomarkers than those with normal albumin levels [33].

This research showed no difference in serum calcium levels after the intervention. Nonetheless, Zhang et al., indicated a rise in serum-ionized calcium levels. Omega-3 might affect bone health by changing calcium absorption and loss [27]. It additionally encourages osteoblastic activity and suppresses the formation of osteoclasts. Moreover, they help estrogen improve bone mineral accumulation [34].

CRP had a positive correlation with serum TBARS. Omega-3 fatty acids modulate inflammation by decreasing the pro-inflammatory cytokines and adhesion molecules [35].

El-Mashad et al. and Omar et al. did not find any change in CRP levels. Variations in the treatment length, sample size, inflammatory markers cutoff values, and patient demographics may cause differing outcomes [28, 32].

We observed a substantial rise in HDL-C levels and a significant reduction in total cholesterol, LDL-C, and TG levels following omega-3 treatment. Additionally, we observed a positive relationship between serum TBARS and triglycerides and LDL-C, as well as a positive association between GSH-Px and HDL-C levels.

Conversely, there was a significant inverse relationship between HDL-C and serum TBARS, as well as an inverse relationship between GSH-Px and LDL-C and triglycerides.

Patients with CKD exhibit a reduced activity of HDL-associated enzymes, which contributes to the impaired antioxidative functions of their HDL-C. Oxidative modifications of Apolipoprotein A-1 lower the transfer of cholesterol to HDL-C3 [36].

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) modulate genes that regulate lipid metabolism, reduce very-low-density lipoprotein triglycerides (VLDL-TG), and enhance triglyceride-rich lipoproteins removal by boosting tissue lipoprotein lipase activity [37].