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.

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CLINICALTRIALS: gov; Unique identifier: NCT04582097.