TY - JOUR
T1 - Renin–angiotensin II–aldosterone system blockers and time to renal replacement therapy in children with CKD
AU - Abraham, Alison G.
AU - Betoko, Aisha
AU - Fadrowski, Jeffrey J.
AU - Pierce, Christopher
AU - Furth, Susan L.
AU - Warady, Bradley A.
AU - Muñoz, Alvaro
N1 - Funding Information:
The authors acknowledge the contributions of all investigators and coordinators in the CKiD Study (www.statepi.jhsph.edu/ckid ), in addition to all participating patients and their families. Data in this manuscript were collected by the CKiD prospective cohort study with clinical coordinating centers (principal investigators) at the Children???s Mercy Hospital and the University of Missouri???Kansas City (Bradley A. Warady, MD) and the Children???s Hospital of Philadelphia (Susan Furth, MD, PhD), the Central Biochemistry Laboratory at the University of Rochester Medical Center (George J. Schwartz, MD), and the data coordinating center at the Johns Hopkins Bloomberg School of Public Health (Alvaro Mu??oz, PhD). The CKiD Study is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung and Blood Institute (grants U01-DK-66143, U01-DK-66174, U01DK-082194, and U01-DK-66116).
PY - 2017/4/1
Y1 - 2017/4/1
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
DO - 10.1007/s00467-016-3512-4
M3 - Article
C2 - 27826732
AN - SCOPUS:84994417774
VL - 32
SP - 643
EP - 649
JO - Pediatric Nephrology
JF - Pediatric Nephrology
SN - 0931-041X
IS - 4
ER -