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

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 BergSalim Çaliskan, 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

Research output: Contribution to journalArticlepeer-review

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 m2 of body-surface area) received ramipril at a dose of 6 mg per square meter of bodysurface 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).

Original languageEnglish
Pages (from-to)1639-1650
Number of pages12
JournalNew England Journal of Medicine
Volume361
Issue number17
DOIs
Publication statusPublished - Oct 22 2009

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Strict blood-pressure control and progression of renal failure in children'. Together they form a unique fingerprint.

Cite this