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Background: Hypertension, endothelial dysfunction, and inflammation are associated with increased cardiovascular mortality in end-stage kidney disease. We evaluated the effects of ACE (angiotensin-converting enzyme) inhibition on biomarkers of endothelial dysfunction and inflammation in hypertensive children with end-stage kidney disease on maintenance hemodialysis. Methods: In a randomized, double-blind, placebo-controlled trial, 135 (72 males/63 females) children and adolescents (age 7–15 years) were randomly assigned to treatment with either 2.5 mg once daily ramipril (n=68) or placebo (n=67) for 16 weeks. Primary outcome were the serum concentrations of asymmetrical dimethylarginine, a marker of endothelial dysfunction and hs-CRP (high-sensitivity C-reactive protein), a marker of inflammation. Changes in IL-6 (interleukin-6), TNF-α (tumor necrosis factor-alpha), systolic (S), and diastolic (D) blood pressure were secondary outcomes. Change in potassium levels and incidence of hyperkalemia were among the safety parameters. Results: Ramipril, but not placebo, significantly reduced serum levels of asymmetrical dimethylarginine (−79.6%; P <0.001), hs-CRP (−46.5%; P <0.001), IL-6 (−27.1%; P <0.001), and TNF-α (−51.7%; P <0.001). Systolic blood pressure and diastolic blood pressure were significantly lowered in both groups with a greater reduction in children receiving ramipril (median between-group differences −12.0 [95% CI −18.0 to −9.5] and −9.0 [95% CI −12.0 to −4.5]; P <0.001, respectively). Changes in asymmetrical dimethylarginine, hs-CRP, IL-6, or TNF-α in the ramipril group did not significantly correlate with blood pressure reductions. No severe cases of hyperkalemia or other serious treatment-associated adverse events were observed. Conclusions: Ramipril improves biomarkers of endothelial dysfunction and inflammation in hypertensive children on maintenance hemodialysis in addition to its efficacious and safe potential to lower blood pressure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04582097.

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<italic>Background:</italic>Chronic kidney disease (CKD) is a worldwide public health problem in the pediatric population. Patients with CKD die of cardiovascular causes rather than from renal disease. There are several traditional and non-traditional risk factors for cardiovascular disease (CVD) in these patients. Endothelial dysfunction is one of the non-traditional risk factors for CVD. Many studies have shown the ability of omega-3 fatty acids to improve the endothelial function and reduce the cardiovascular events in the general population. Thus, the aim of this study was to evaluate the effect of omega-3 fatty acids supplementation on markers of endothelial dysfunction in children with CKD on regular hemodialysis (HD). <italic>Methods and procedures:</italic> This double-blinded randomized placebo-controlled trial included 49 pediatric patients on maintenance HD. Group 1 (n=25) received 1 g omega-3 capsule once daily and group 2 (n=24) received 1 g matched placebo capsule once daily. Both groups were treated for four months. Blood samples were taken from patients of both groups at baseline and after 4 months of supplementation. Serum samples were examined for C-reactive protein (CRP) and nitric oxide (NO) levels as markers of endothelial dysfunction. <italic>Results:</italic> Our results showed that CRP was reduced insignificantly in omega-3 group. NO levels showed no significant differences between groups at the end of the study. <italic>Conclusion:</italic> The administration of 1 g omega-3 capsule once daily for 4 months had no beneficial effects neither on CRP nor NO but should evaluate more.

The study including 3703 patients with confirmed coronavirus disease 2019 revealed that older age, male gender, or having more than two comorbidities were associated with increased morbidity and mortality. We are in total agreement with these findings and want to represent suggested mechanisms that can clarify the results especially regarding chronic kidney disease (CKD) as a comorbidity.As COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spreads throughout the world, almost every individual is at risk for infection. However, some patients are at risk for severe illness and death. Old age and underlying comorbid conditions were associated with increased COVID-19 severity and mortality. 2 The most important comorbidities were hypertension (HTN) (9.5%-31.2%), diabetes mellitus (8.2%-20%), and other cardiovascular and cerebrovascular diseases (5.6%-40%). Regarding chronic kidney disease (CKD), its prevalence in patients with COVID-19 was 0%-5.6%. Based on this minor percentage, it was uncertain whether CKD should be considered as a true risk factor for COVID-19. Several studies have been conducted to evaluate the correlation between the two pandemics. Although Gerwen et al. 1 study did not document an association between CKD comorbidity and COVID-19 poor outcomes, many studies reported a positive association between CKD and COVID-19 severity and mortality. [3][4][5] The authors declare that there is no conflict of interests.

Background and Aims Endothelial dysfunction is an important risk factor for cardiovascular disease and therefore for increased mortality in end-stage renal disease patients. Asymmetric dimethyl arginine (ADMA), a potent inhibitor of nitric oxide synthase, strongly contributes to endothelial dysfunction. In dialysis patients, ADMA levels are markedly elevated. Previous studies have shown that angiotensin-converting enzyme inhibitors (ACEIs) can significantly reduce ADMA levels in a variety of patients. In contrast, a previous study suggested that short-term treatment with ACEIs may even increase ADMA levels in adult patients on maintenance hemodialysis. However, no study has evaluated the effect of ACEIs in pediatric patients undergoing hemodialysis. Method We conducted a prospective, randomized, double-blinded and placebo-controlled trial (NCT04582097) at two nephrology centers in Cairo, Egypt. Patients below the age of 16 years and on regular hemodialysis for 6 months or longer were eligible for inclusion. Exclusion criteria at screening included uncontrolled hypertension, serum potassium level &gt; 5.5 mmol/L, acute infection or treatment with immunosuppressive agents within the previous month, known intolerance of ACEI treatment and inability to discontinue previous ACEI or angiotensin receptor blocker treatment. A total of 135 eligible patients (mean age, 12.6 years; range 7-15 years; 53.3% males) were randomly (1:1) assigned to once oral daily treatment with identical capsules containing either 2.5 mg ramipril (n=68) or placebo (n=67) for four months. Systolic and diastolic blood pressure (BP) and serum ADMA concentrations were measured as primary efficacy and serum potassium levels as primary safety parameter. Results At baseline, systolic and diastolic BP and ADMA levels were similar between both treatment groups (Table). After four months, both systolic and diastolic BP were significantly lower in the ramipril compared to the placebo group. Treatment with ramipril resulted in a profound reduction in ADMA levels (-77% compared to baseline) while ADMA levels were unchanged in the placebo group after four months (p &lt;0.001). Serum levels of potassium increase in both groups with no reported symptoms of severe hyperkalemia No serious adverse events were reported in neither group. Conclusion Ramipril treatment in pediatric patients on maintenance hemodialysis causes a marked reduction in ADMA levels. This may contribute to improved endothelial vascular function besides its efficacious BP lowering effect.

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