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, P. Sallay, Nikola Jeck, Ulla Berg & 15 others Salim 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 journalArticle

493 Citations (Scopus)

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

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Renal Insufficiency
Blood Pressure
Glomerular Filtration Rate
Chronic Renal Insufficiency
Proteinuria
Peptidyl-Dipeptidase A
Renin-Angiotensin System
Kidney
Arterial Pressure
Ramipril
Safety Management
Body Surface Area
Kaplan-Meier Estimate
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Chronic Kidney Failure
Disease Progression
Reference Values
Confidence Intervals
Incidence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wühl, E., Trivelli, A., Picca, S., Litwin, M., Peco-Antic, A., Zurowska, A., ... Schaefer, F. (2009). Strict blood-pressure control and progression of renal failure in children. New England Journal of Medicine, 361(17), 1639-1650. https://doi.org/10.1056/NEJMoa0902066

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, P.; Jeck, Nikola; Berg, Ulla; Çaliskan, 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.

In: New England Journal of Medicine, Vol. 361, No. 17, 22.10.2009, p. 1639-1650.

Research output: Contribution to journalArticle

Wühl, E, Trivelli, A, Picca, S, Litwin, M, Peco-Antic, A, Zurowska, A, Testa, S, Jankauskiene, A, Emre, S, Caldas-Afonso, A, Anarat, A, Niaudet, P, Mir, S, Bakkaloglu, A, Enke, B, Montini, G, Wingen, AM, Sallay, P, Jeck, N, Berg, U, Çaliskan, S, Wygoda, S, Hohbach-Hohenfellner, K, Dusek, J, Urasinski, T, Arbeiter, K, Neuhaus, T, Gellermann, J, Drozdz, D, Fischbach, M, Möller, K, Wigger, M, Peruzzi, L, Mehls, O & Schaefer, F 2009, 'Strict blood-pressure control and progression of renal failure in children', New England Journal of Medicine, vol. 361, no. 17, pp. 1639-1650. https://doi.org/10.1056/NEJMoa0902066
Wühl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, Zurowska A et al. Strict blood-pressure control and progression of renal failure in children. New England Journal of Medicine. 2009 Oct 22;361(17):1639-1650. https://doi.org/10.1056/NEJMoa0902066
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, P. ; Jeck, Nikola ; Berg, Ulla ; Çaliskan, 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. / Strict blood-pressure control and progression of renal failure in children. In: New England Journal of Medicine. 2009 ; Vol. 361, No. 17. pp. 1639-1650.
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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).",
author = "Elke W{\"u}hl and Antonella Trivelli and Stefano Picca and Mieczyslaw Litwin and Amira Peco-Antic and Aleksandra Zurowska and Sara Testa and Augustina Jankauskiene and Sevinc Emre and Alberto Caldas-Afonso and Ali Anarat and Patrick Niaudet and Sevgi Mir and Aysin Bakkaloglu and Barbara Enke and Giovanni Montini and Wingen, {Ann Margret} and P. Sallay and Nikola Jeck and Ulla Berg and Salim {\cC}aliskan and Simone Wygoda and Katharina Hohbach-Hohenfellner and Jiri Dusek and Tomasz Urasinski and Klaus Arbeiter and Thomas Neuhaus and Jutta Gellermann and Dorota Drozdz and Michel Fischbach and Kristina M{\"o}ller and Marianne Wigger and Licia Peruzzi and Otto Mehls and Franz Schaefer",
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TY - JOUR

T1 - Strict blood-pressure control and progression of renal failure in children

AU - Wühl, Elke

AU - Trivelli, Antonella

AU - Picca, Stefano

AU - Litwin, Mieczyslaw

AU - Peco-Antic, Amira

AU - Zurowska, Aleksandra

AU - Testa, Sara

AU - Jankauskiene, Augustina

AU - Emre, Sevinc

AU - Caldas-Afonso, Alberto

AU - Anarat, Ali

AU - Niaudet, Patrick

AU - Mir, Sevgi

AU - Bakkaloglu, Aysin

AU - Enke, Barbara

AU - Montini, Giovanni

AU - Wingen, Ann Margret

AU - Sallay, P.

AU - Jeck, Nikola

AU - Berg, Ulla

AU - Çaliskan, Salim

AU - Wygoda, Simone

AU - Hohbach-Hohenfellner, Katharina

AU - Dusek, Jiri

AU - Urasinski, Tomasz

AU - Arbeiter, Klaus

AU - Neuhaus, Thomas

AU - Gellermann, Jutta

AU - Drozdz, Dorota

AU - Fischbach, Michel

AU - Möller, Kristina

AU - Wigger, Marianne

AU - Peruzzi, Licia

AU - Mehls, Otto

AU - Schaefer, Franz

PY - 2009/10/22

Y1 - 2009/10/22

N2 - 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).

AB - 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).

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