Renin–angiotensin II–aldosterone system blockers and time to renal replacement therapy in children with CKD

Alison Gump Abraham, Aisha Betoko, Jeffrey J. Fadrowski, Christopher Pierce, Susan L. Furth, Bradley A. Warady, Alvaro Munoz

Research output: Contribution to journalArticle

Abstract

Background: Clinical care decisions to treat chronic kidney disease (CKD) in a growing child must often be made without the benefit of evidence from clinical trials. We used observational data from the Chronic Kidney Disease in Children cohort to estimate the effectiveness of renin–angiotensin II–aldosterone system blockade (RAAS) to delay renal replacement therapy (RRT) in children with CKD. Methods: A total of 851 participants (median age: 11 years, median glomerular filtration rate [GFR]: 52 ml/min/1.73 m2, median urine protein to creatinine ratio: 0.35 mg/mg) were included. RAAS use was reported at annual study visits. Both Cox proportional hazards models with time-varying RAAS exposure and Cox marginal structural models (MSM) were used to evaluate the effect of RAAS use on time to RRT. Analyses were adjusted or weighted to control for age, male sex, glomerular diagnosis, GFR, nephrotic range proteinuria, anemia, elevated blood pressure, acidosis, elevated phosphate and elevated potassium. Results: There were 217 RRT events over a 4.1-year median follow-up. At baseline, 472 children (55 %) were prevalent RAAS users, who were more likely to be older, have a glomerular etiology, have higher urine protein, be anemic, have elevated serum phosphate and potassium, take more medications, but less likely to have elevated blood pressure, compared with non-users. RAAS use was found to reduce the risk of RRT by 21 % (hazard ratio: 0.79) to 37 % (hazard ratio: 0.63) from standard regression adjustment and MSM models, respectively. Conclusions: These results support inferences from adult studies of a substantial benefit of RAAS use in pediatric CKD patients.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalPediatric Nephrology
DOIs
StateAccepted/In press - Nov 8 2016

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Renal Replacement Therapy
Chronic Renal Insufficiency
Structural Models
Glomerular Filtration Rate
Urine
Blood Pressure
Acidosis
Proteinuria
Proportional Hazards Models
Anemia
Creatinine
Proteins
Clinical Trials
Pediatrics
Serum
potassium phosphate

Keywords

  • ACE inhibitor
  • Chronic kidney disease
  • End-stage renal disease
  • Marginal structural model
  • Renal replacement therapy
  • Renin–angiotensin system
  • Time-varying covariates

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

Cite this

@article{21a831dd47ee4588a57430b27673f187,
title = "Renin–angiotensin II–aldosterone system blockers and time to renal replacement therapy in children with CKD",
abstract = "Background: Clinical care decisions to treat chronic kidney disease (CKD) in a growing child must often be made without the benefit of evidence from clinical trials. We used observational data from the Chronic Kidney Disease in Children cohort to estimate the effectiveness of renin–angiotensin II–aldosterone system blockade (RAAS) to delay renal replacement therapy (RRT) in children with CKD. Methods: A total of 851 participants (median age: 11 years, median glomerular filtration rate [GFR]: 52 ml/min/1.73 m2, median urine protein to creatinine ratio: 0.35 mg/mg) were included. RAAS use was reported at annual study visits. Both Cox proportional hazards models with time-varying RAAS exposure and Cox marginal structural models (MSM) were used to evaluate the effect of RAAS use on time to RRT. Analyses were adjusted or weighted to control for age, male sex, glomerular diagnosis, GFR, nephrotic range proteinuria, anemia, elevated blood pressure, acidosis, elevated phosphate and elevated potassium. Results: There were 217 RRT events over a 4.1-year median follow-up. At baseline, 472 children (55 {\%}) were prevalent RAAS users, who were more likely to be older, have a glomerular etiology, have higher urine protein, be anemic, have elevated serum phosphate and potassium, take more medications, but less likely to have elevated blood pressure, compared with non-users. RAAS use was found to reduce the risk of RRT by 21 {\%} (hazard ratio: 0.79) to 37 {\%} (hazard ratio: 0.63) from standard regression adjustment and MSM models, respectively. Conclusions: These results support inferences from adult studies of a substantial benefit of RAAS use in pediatric CKD patients.",
keywords = "ACE inhibitor, Chronic kidney disease, End-stage renal disease, Marginal structural model, Renal replacement therapy, Renin–angiotensin system, Time-varying covariates",
author = "Abraham, {Alison Gump} and Aisha Betoko and Fadrowski, {Jeffrey J.} and Christopher Pierce and Furth, {Susan L.} and Warady, {Bradley A.} and Alvaro Munoz",
year = "2016",
month = "11",
day = "8",
doi = "10.1007/s00467-016-3512-4",
language = "English (US)",
pages = "1--7",
journal = "Pediatric Nephrology",
issn = "0931-041X",
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TY - JOUR

T1 - Renin–angiotensin II–aldosterone system blockers and time to renal replacement therapy in children with CKD

AU - Abraham, Alison Gump

AU - Betoko, Aisha

AU - Fadrowski, Jeffrey J.

AU - Pierce, Christopher

AU - Furth, Susan L.

AU - Warady, Bradley A.

AU - Munoz, Alvaro

PY - 2016/11/8

Y1 - 2016/11/8

N2 - Background: Clinical care decisions to treat chronic kidney disease (CKD) in a growing child must often be made without the benefit of evidence from clinical trials. We used observational data from the Chronic Kidney Disease in Children cohort to estimate the effectiveness of renin–angiotensin II–aldosterone system blockade (RAAS) to delay renal replacement therapy (RRT) in children with CKD. Methods: A total of 851 participants (median age: 11 years, median glomerular filtration rate [GFR]: 52 ml/min/1.73 m2, median urine protein to creatinine ratio: 0.35 mg/mg) were included. RAAS use was reported at annual study visits. Both Cox proportional hazards models with time-varying RAAS exposure and Cox marginal structural models (MSM) were used to evaluate the effect of RAAS use on time to RRT. Analyses were adjusted or weighted to control for age, male sex, glomerular diagnosis, GFR, nephrotic range proteinuria, anemia, elevated blood pressure, acidosis, elevated phosphate and elevated potassium. Results: There were 217 RRT events over a 4.1-year median follow-up. At baseline, 472 children (55 %) were prevalent RAAS users, who were more likely to be older, have a glomerular etiology, have higher urine protein, be anemic, have elevated serum phosphate and potassium, take more medications, but less likely to have elevated blood pressure, compared with non-users. RAAS use was found to reduce the risk of RRT by 21 % (hazard ratio: 0.79) to 37 % (hazard ratio: 0.63) from standard regression adjustment and MSM models, respectively. Conclusions: These results support inferences from adult studies of a substantial benefit of RAAS use in pediatric CKD patients.

AB - Background: Clinical care decisions to treat chronic kidney disease (CKD) in a growing child must often be made without the benefit of evidence from clinical trials. We used observational data from the Chronic Kidney Disease in Children cohort to estimate the effectiveness of renin–angiotensin II–aldosterone system blockade (RAAS) to delay renal replacement therapy (RRT) in children with CKD. Methods: A total of 851 participants (median age: 11 years, median glomerular filtration rate [GFR]: 52 ml/min/1.73 m2, median urine protein to creatinine ratio: 0.35 mg/mg) were included. RAAS use was reported at annual study visits. Both Cox proportional hazards models with time-varying RAAS exposure and Cox marginal structural models (MSM) were used to evaluate the effect of RAAS use on time to RRT. Analyses were adjusted or weighted to control for age, male sex, glomerular diagnosis, GFR, nephrotic range proteinuria, anemia, elevated blood pressure, acidosis, elevated phosphate and elevated potassium. Results: There were 217 RRT events over a 4.1-year median follow-up. At baseline, 472 children (55 %) were prevalent RAAS users, who were more likely to be older, have a glomerular etiology, have higher urine protein, be anemic, have elevated serum phosphate and potassium, take more medications, but less likely to have elevated blood pressure, compared with non-users. RAAS use was found to reduce the risk of RRT by 21 % (hazard ratio: 0.79) to 37 % (hazard ratio: 0.63) from standard regression adjustment and MSM models, respectively. Conclusions: These results support inferences from adult studies of a substantial benefit of RAAS use in pediatric CKD patients.

KW - ACE inhibitor

KW - Chronic kidney disease

KW - End-stage renal disease

KW - Marginal structural model

KW - Renal replacement therapy

KW - Renin–angiotensin system

KW - Time-varying covariates

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U2 - 10.1007/s00467-016-3512-4

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