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. (ClinicalTrials.gov number, NCT00221845 [ClinicalTrials.gov] .)
The members of the writing committee (Elke Wühl, M.D., Antonella Trivelli, M.D., Stefano Picca, M.D., Mieczyslaw Litwin, M.D., Amira Peco-Antic, M.D., Aleksandra Zurowska, M.D., Sara Testa, M.D., Augustina Jankauskiene, M.D., Sevinc Emre, M.D., Alberto Caldas-Afonso, M.D., Ali Anarat, M.D., Patrick Niaudet, M.D., Sevgi Mir, M.D., Aysin Bakkaloglu, M.D., Barbara Enke, M.D., Giovanni Montini, M.D., Ann-Margret Wingen, M.D., Peter Sallay, M.D., Nikola Jeck, M.D., Ulla Berg, M.D., Salim Çaliskan, M.D., Simone Wygoda, M.D., Katharina Hohbach-Hohenfellner, M.D., Jiri Dusek, M.D., Tomasz Urasinski, M.D., Klaus Arbeiter, M.D., Thomas Neuhaus, M.D., Jutta Gellermann, M.D., Dorota Drozdz, M.D., Michel Fischbach, M.D., Kristina Möller, M.D., Marianne Wigger, M.D., Licia Peruzzi, M.D., Otto Mehls, M.D., and Franz Schaefer, M.D.) assume responsibility for the overall content and integrity of the article. The affiliations of the members of the writing committee are listed in the Appendix.