Strict Blood-Pressure Control and Progression of Renal Failure in Children

The ESCAPE Trial Group

Background Although inhibition of the renin–angiotensin system delays
the progression of renal failure in adults with chronic kidney
disease, the blood-pressure target for optimal renal protection is
controversial. We assessed the long-term renoprotective effect of
intensified blood-pressure control among children who were receiving a
fixed high dose of an angiotensin-converting–enzyme (ACE) inhibitor.

Methods After a 6-month run-in period, 385 children, 3 to 18 years of
age, with chronic kidney disease (glomerular filtration rate of 15 to
80 ml per minute per 1.73 m2 of body-surface area) received ramipril
at a dose of 6 mg per square meter of body-surface area per day.
Patients were randomly assigned to intensified blood-pressure control
(with a target 24-hour mean arterial pressure below the 50th
percentile) or conventional blood-pressure control (mean arterial
pressure in the 50th to 95th percentile), achieved by the addition of
antihypertensive therapy that does not target the renin–angiotensin
system; patients were followed for 5 years. The primary end point was
the time to a decline of 50% in the glomerular filtration rate or
progression to end-stage renal disease. Secondary end points included
changes in blood pressure, glomerular filtration rate, and urinary
protein excretion.

Results A total of 29.9% of the patients in the group that received
intensified blood-pressure control reached the primary end point, as
assessed by means of a Kaplan–Meier analysis, as compared with 41.7%
in the group that received conventional blood-pressure control (hazard
ratio, 0.65; confidence interval, 0.44 to 0.94; P=0.02). The two
groups did not differ significantly with respect to the type or
incidence of adverse events or the cumulative rates of withdrawal from
the study (28.0% vs. 26.5%). Proteinuria gradually rebounded during
ongoing ACE inhibition after an initial 50% decrease, despite
persistently good blood-pressure control. Achievement of
blood-pressure targets and a decrease in proteinuria were significant
independent predictors of delayed progression of renal disease.

Conclusions Intensified blood-pressure control, with target 24-hour
blood-pressure levels in the low range of normal, confers a
substantial benefit with respect to renal function among children with
chronic kidney disease. Reappearance of proteinuria after initial
successful pharmacologic blood-pressure control is common among
children who are receiving long-term ACE inhibition