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

Pediatr Nephrol. 2017 Apr;32(4):643-649. doi: 10.1007/s00467-016-3512-4. Epub 2016 Nov 8.


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.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Child
  • Cohort Studies
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Male
  • Proteinuria / etiology
  • Proteinuria / therapy
  • Renal Insufficiency, Chronic / therapy*
  • Renal Replacement Therapy / statistics & numerical data*
  • Renin-Angiotensin System / drug effects*
  • Risk Factors
  • Socioeconomic Factors
  • Time-to-Treatment
  • Treatment Outcome


  • Angiotensin II Type 1 Receptor Blockers