Effect of ramipril on ambulatory blood pressure and albuminuria in renal hypertension

Abstract

Inhibition of the angiotensin-converting enzyme (ACE) exerts a renoprotective effect in adult patients with chronic kidney disease. We evaluated prospectively changes in blood pressure (BP), protein excretion and renal function after administration of the long-acting ACE inhibitor ramipril as monotherapy during 6 months in 14 moderately hypertensive children aged 5-18 years with various nephropathies. Four patients initially had a decreased glomerular filtration rate (GFR below 60 ml/min/1.73 m2). BP was evaluated by ambulatory 24-h monitoring. After 2 weeks of treatment by oral ramipril (1.5 mg/m2 once daily), mean values of systolic and diastolic 24-h ambulatory BP fell by more than 5 mmHg in nine patients. In eight patients the dose was doubled. At the end of the study systolic BP was below the 95th percentile in 9 and diastolic BP in 13 patients. The initially reduced nocturnal dip increased significantly. Of 11 patients with an increased albumin excretion (median 1.3 g/g creatinine), 6 responded to ramipril by a median reduction of 78% (range 24-83%), whilst in 5 albuminuria increased (median +19%). GFR was well preserved and no other adverse effects from the drug were noted. The study demonstrates that ramipril is an efficacious antihypertensive agent in children with renal hypertension. It is well tolerated, even in mild renal insufficiency. In addition, the drug has a persistent antiproteinuric action in about half of the patients contributing to conserve renal function.

Association of Proteinuria with Race, Cause of Chronic Kidney Disease, and Glomerular Filtration Rate in the Chronic Kidney Disease in Children Study

“…In this group of subjects, we demonstrated differences in level of Up/c with patients reporting RAS antagonist use having lower levels of proteinuria compared with patients not using these medications. These findings are consistent with other reports documenting the anti-proteinuric efficacy of these agents in the pediatric CKD population (5,27,28,29). Subjects with nonglomerular disease had significantly lower levels of Up/c compared with subjects with glomerular causes of CKD.…”

Relationship Between Diurnal Blood Pressure, Renal Hemodynamic Function, and the Renin-Angiotensin System in Type 1 Diabetes

“…Our third major finding was the observation that, as previously documented, ACE inhibition resulted in a correction of the abnormal N/D ratio (26), but it did not ameliorate glomerular hyperfiltration. Recent data from Hollenberg et al (29) demonstrated that 80% of subjects with type 1 diabetes in their study exhibited evidence of intrarenal RAS activation, as suggested by a vigorous renal vasodilator response to ACE inhibition and Ang II receptor blockade.…”

“…Although the mechanism(s) responsible for these associations have not been fully elucidated, subjects with uncomplicated type 1 diabetes and high N/D ratio exhibit higher values for GFR in comparison to subjects with a normal N/D ratio (21), and renal hyperfiltration is a risk factor for diabetic nephropathy (22)(23)(24)(25). In one study (26) high N/D ratio was corrected by ACE inhibition, suggesting a role for renin angiotensin system (RAS) activation in this phenomenon. Because of the central role played by the RAS in the pathophysiology of diabetic nephropathy (27)(28)(29), we hypothesized that RAS activation may explain both the nondipping phenotype and the poor outcomes.…”

Ambulatory Blood Pressure Monitoring in Children and Adolescents: Recommendations for Standard Assessment

“…13 In a small study of 14 children with renal hypertension, ABPM readings proved that treatment with ramipril was effective in lowering 24-hour average BP while also improving nocturnal dipping. 123 In a separate trial of 21 adolescents, ABPM was used to demonstrate the efficacy of amlodipine, a calcium channel blocker, as an effective once-daily antihypertensive agent. 124 Despite the paucity of data on the use of ABPM in monitoring hypertensive treatment in children, a recent survey of 438 North American pediatric nephrologists found that the majority favor use of ABPM for this purpose.…”