Strict blood-pressure control and progression of renal failure in children
ESCAPE Trial Group, Elke Wühl, Antonella Trivelli, Stefano Picca, Mieczyslaw Litwin, Amira Peco-Antic, Aleksandra Zurowska, Sara Testa, Augustina Jankauskiene, Sevinc Emre, Alberto Caldas-Afonso, Ali Anarat, Patrick Niaudet, Sevgi Mir, Aysin Bakkaloglu, Barbara Enke, Giovanni Montini, Ann-Margret Wingen, Peter Sallay, Nikola Jeck, Ulla Berg, Salim Caliskan, Simone Wygoda, Katharina Hohbach-Hohenfellner, Jiri Dusek, Tomasz Urasinski, Klaus Arbeiter, Thomas Neuhaus, Jutta Gellermann, Dorota Drozdz, Michel Fischbach, Kristina Möller, Marianne Wigger, Licia Peruzzi, Otto Mehls, Franz Schaefer, F Schaefer, O Mehls, E Wühl, C Gimpel, F Schaefer, E Wühl, C Gimpel, F Ozaltin, U Querfeld, K-E Bonzel, I Balasz, F Perfumo, D E Müller-Wiefel, G Offner, C Gimpel, G Klaus, G Ardissino, M Charbit, A Fernandes-Teixeira, M C Matteucci, A Mastrostefano, G Celsi, J Terzic, J Fydryk, R Coppo, R Grenda, R Janas, ESCAPE Trial Group, Elke Wühl, Antonella Trivelli, Stefano Picca, Mieczyslaw Litwin, Amira Peco-Antic, Aleksandra Zurowska, Sara Testa, Augustina Jankauskiene, Sevinc Emre, Alberto Caldas-Afonso, Ali Anarat, Patrick Niaudet, Sevgi Mir, Aysin Bakkaloglu, Barbara Enke, Giovanni Montini, Ann-Margret Wingen, Peter Sallay, Nikola Jeck, Ulla Berg, Salim Caliskan, Simone Wygoda, Katharina Hohbach-Hohenfellner, Jiri Dusek, Tomasz Urasinski, Klaus Arbeiter, Thomas Neuhaus, Jutta Gellermann, Dorota Drozdz, Michel Fischbach, Kristina Möller, Marianne Wigger, Licia Peruzzi, Otto Mehls, Franz Schaefer, F Schaefer, O Mehls, E Wühl, C Gimpel, F Schaefer, E Wühl, C Gimpel, F Ozaltin, U Querfeld, K-E Bonzel, I Balasz, F Perfumo, D E Müller-Wiefel, G Offner, C Gimpel, G Klaus, G Ardissino, M Charbit, A Fernandes-Teixeira, M C Matteucci, A Mastrostefano, G Celsi, J Terzic, J Fydryk, R Coppo, R Grenda, R Janas
Abstract
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 m(2) 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. (ClinicalTrials.gov number, NCT00221845.)
2009 Massachusetts Medical Society
Source: PubMed