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Strict blood-pressure control and progression of renal failure in children.

Wühl, Elke; Trivelli, Antonella; Picca, Stefano; Litwin, Mieczyslaw; Peco-Antic, Amira; Zurowska, Aleksandra; Testa, Sara; Jankauskiene, Augustina; Emre, Sevinc; Caldas-Afonso, Alberto; Anarat, Ali; Niaudet, Patrick; Mir, Sevgi; Bakkaloglu, Aysin; Enke, Barbara; Montini, Giovanni; Wingen, Ann-Margret; Sallay, Peter; Jeck, Nikola; Berg, Ulla; Caliskan, Salim; Wygoda, Simone; Hohbach-Hohenfellner, Katharina; Dusek, Jiri; Urasinski, Tomasz; Arbeiter, Klaus; Neuhaus, Thomas; Gellermann, Jutta; Drozdz, Dorota; Fischbach, Michel; Möller, Kristina; Wigger, Marianne; Peruzzi, Licia; Mehls, Otto; Schaefer, Franz.
N Engl J Med; 361(17): 1639-50, 2009 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-19846849


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.


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.


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.


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. ( number, NCT00221845.)
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