Effects of Ramipril on Biomarkers of Endothelial Dysfunction and Inflammation in Hypertensive Children on Maintenance Hemodialysis: the SEARCH Randomized Placebo-Controlled Trial.

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.

Effect of Omega-3 Fatty Acids on Serum Lipid Profile and Oxidative Stress in Pediatric Patients on Regular Hemodialysis: A Randomized Placebo-Controlled Study.

OBJECTIVE: We sought to evaluate the effects of omega-3 fatty acids supplementation on serum lipid profile and oxidative stress markers in pediatric patients with end-stage renal disease on regular hemodialysis (HD). DESIGN: This study was a double-blinded, randomized, placebo-controlled trial conducted on 49 pediatric patients on regular HD for at least 6 months. INTERVENTION: Patients were randomly divided into either omega-3 group (n = 25) who received 1-g oral omega-3 capsule once daily for 16 weeks or placebo group (n = 24) who received 1-g matching oral placebo capsule once daily for 16 weeks. MAIN OUTCOME MEASURE: Lipid profile markers including: total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and oxidative stress markers including the following: malondialdehyde, glutathione peroxidase, and superoxide dismutase were measured at baseline and after 16 weeks of supplementation. RESULTS: By the end of the study, children in omega-3 group showed a highly significant reduction in total cholesterol and a highly significant increase in glutathione peroxidase and superoxide dismutase levels. CONCLUSION: The administration of omega-3 has a beneficial effect on serum lipid profile and oxidative stress in children undergoing HD.