Antihypertensive and antiproteinuric efficacy of ramipril in children with chronic renal failure.
BACKGROUND
While the antihypertensive and renoprotective potency of angiotensin-converting enzyme (ACE) inhibitors is well-established in adults with hypertension and/or chronic renal failure, little experience exists in pediatric chronic kidney disease.


METHODS
As part of a prospective assessment of the renoprotective efficacy of ACE inhibition and intensified blood pressure (BP) control, 397 children (ages 3 to 18 years) with chronic renal failure [CRF; glomerular filtration rate (GFR) 11 to 80 mL/min/1.73 m2] and elevated or high-normal BP received ramipril (6 mg/m2) following a 6-month run-in period including a two-month washout of any previous ACE inhibitors. Drug efficacy was assessed by two monthly office BP and proteinuria assessments, and by ambulatory BP monitoring at start and after 6 months of treatment.


RESULTS
In the 352 patients completing six months of treatment, 24-hour mean arterial pressure (MAP) had decreased by a mean of 11.5 mm Hg (-2.2 SDS) in initially hypertensive subjects, but only by 4.4 mm Hg (-0.8 SDS) in patients with initially normal BP. A linear correlation was found between MAP at baseline and the change of MAP during treatment (r= 0.51; P < 0.0001). The antihypertensive response was independent of changes in concomitant antihypertensive medication or underlying renal disease. BP was reduced with equal efficacy during day- and nighttime. Urinary protein excretion was reduced by 50% on average, with similar relative efficacy in patients with hypo/dysplastic nephropathies and glomerulopathies. The magnitude of proteinuria reduction depended on baseline proteinuria (r= 0.32, P < 0.0001), and was correlated with the antihypertensive efficacy of the drug (r= 0.22, P < 0.001). The incidence of rapid rises in serum creatinine and progression to end-stage CRF during treatment did not differ from the pretreatment observation period. Mean serum potassium increased by 0.3 mmol/L. Ramipril was discontinued in three patients due to symptomatic hypotension or hyperkalemia. Hemoglobin levels decreased by 0.6 g/dL in the first two treatment months and remained stable thereafter.


CONCLUSIONS
Ramipril appears to be an effective and safe antihypertensive and antiproteinuric agent in children with CRF-associated hypertension. The BP lowering and antiproteinuric effects are greatest in severely hypertensive and proteinuric children.
Wühl
Elke
E
Division of Pediatric Nephrology, University Children's Hospital, University of Heidelberg, Heidelberg, Germany.
Mehls
Otto
O
Schaefer
Franz
F
D000293:Adolescent; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D006801:Humans; D006977:Hypertension, Renal / Q000188:drug therapy; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy*; D017257:Ramipril / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D017257:Ramipril