MO1008IMPACT OF RAMIPRIL ON ENDOTHELIAL DYSFUNCTION IN CHILDREN ON REGULAR HEMODIALYSIS

Abstract 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 > 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 <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.