Skip to main content

Advertisement

SpringerLink
Log in

Angiotensin-Converting Enzyme Inhibitor Nephrotoxicity in Neonates with Cardiac Disease

  • Original Article
  • Published:
Pediatric Cardiology Aims and scope Submit manuscript

Abstract

Angiotensin-converting enzyme inhibitors (ACEi) are commonly used for pediatric cardiology patients. However, studies examining their safety for neonates with cardiac disease are scarce. The current study aimed to test the hypothesis that ACEi-mediated nephrotoxicity occurs in neonates and may be underappreciated in this population. A retrospective review of 243 neonates with cardiac disease between 2007 and 2010 was performed. Demographic data, weight, length, captopril and enalapril dosing, serum [K+], serum creatinine, and concomitant medications during ACEi therapy were recorded and analyzed. Body surface area (BSA), creatinine clearance (CrCl), and change in [K+] were calculated. The age range of neonates at ACEi initiation was 15.9–18.1 days. The inclusion criteria was met by 206 neonates: 168 term (82 %) and 38 preterm (18 %) newborns. Of these neonates, 42 % were female, and all the patients had a BSA smaller than 0.33 m2 (a group known to have relative renal insufficiency). The mean dose of enalapril was 0.08 ± 0.007 mg/kg for the preterm neonates and 0.08 ± 0.003 mg/kg for the term neonates. The mean dose of captopril was 0.07 ± 0.009 mg/kg for the preterm neonates and 0.13 ± 0.019 mg/kg for the term neonates. A significant decrease in CrCl occurred for both the preterm (p < 0.01) and term (p < 0.001) neonates while they were receiving ACEi. However, the two groups did not differ significantly (p = 0.183). Nearly 42 % of all the patients showed renal risk, with approximately 30 % demonstrating renal failure by modified pRIFLE (pediatric risk, injury, failure, loss, and end-stage renal disease) criteria. Despite the lack of significantly different CrCl, the premature neonates were more likely to experience ACEi-related renal failure by pRIFLE (55 %) than their term counterparts (23 %; p < 0.001). Despite its common use for term neonates with cardiac disease, ACEi should be used cautiously and only when indications are clear. These results also raise the question whether ACEi should be used at all for preterm neonates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ahmed A (2002) Use of angiotensin-converting enzyme inhibitors in patients with heart failure and renal insufficiency: how concerned should we be by the rise in serum creatinine? J Am Geriatr Soc 50:1297–1300

    Article  PubMed  Google Scholar 

  2. Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL (2007) Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 71:1028–1035

    Article  CAS  PubMed  Google Scholar 

  3. Bakris GL, Weir MR (2000) Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med 160:685–693

    Article  CAS  PubMed  Google Scholar 

  4. Clark BJ III (2000) Treatment of heart failure in infants and children. Heart Dis 2:354–361

    CAS  PubMed  Google Scholar 

  5. Diav-Citrin O, Shechtman S, Halberstadt Y, Finkel-Pekarsky V, Wajnberg R, Arnon J et al (2011) Pregnancy outcome after in utero exposure to angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Reprod Toxicol 31:540–545

    Article  CAS  PubMed  Google Scholar 

  6. Dittrich S, Kurschat K, Dahnert I, Vogel M, Muller C, Alexi-Meskishvili V et al (2000) Renal function after cardiopulmonary bypass surgery in cyanotic congenital heart disease. Int J Cardiol 73:173–179

    Article  CAS  PubMed  Google Scholar 

  7. Gantenbein MH, Bauersfeld U, Baenziger O, Frey B, Neuhaus T, Sennhauser F et al (2008) Side effects of angiotensin-converting enzyme inhibitor (captopril) in newborns and young infants. J Perinat Med 36:448–452

    Article  CAS  PubMed  Google Scholar 

  8. Haycock GB, Schwartz GJ, Wisotsky DH (1978) Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults. J Pediatr 93:62–66

    Article  CAS  PubMed  Google Scholar 

  9. Hsu DT, Zak V, Mahony L, Sleeper LA, Atz AM, Levine JC et al (2010) Enalapril in infants with single ventricle: results of a multicenter randomized trial. Circulation 122:333–340

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Kist-van Holthe tot Echten JE, Goedvolk CA, Doornaar MB, van der Vorst MM, Bosman-Vermeeren JM, Brand R et al (2001) Acute renal insufficiency and renal replacement therapy after pediatric cardiopulmonary bypass surgery. Pediatr Cardiol 22:321–326

    Article  CAS  PubMed  Google Scholar 

  11. Lee GJ, Cohen R, Chang AC, Cleary JP (2010) Angiotensin-converting enzyme inhibitor (ACEI)-induced acute renal failure in premature newborns with congenital heart disease. J Pediatr Pharmacol Ther 15:290–296

    PubMed Central  PubMed  Google Scholar 

  12. Lee KJ, Yoo SJ, Holtby H, Grant B, Mroczek D, Wong D et al (2011) Acute effects of the ACE inhibitor enalaprilat on the pulmonary, cerebral, and systemic blood flow and resistance after the bidirectional cavopulmonary connection. Heart 97:1343–1348

    Article  CAS  PubMed  Google Scholar 

  13. Markfeld-Erol F, Farthmann J, Prompeler H, Kunze M (2012) Fetal renal failure after intrauterine exposure to inhibitors of the renin-angiotensin system. Dtsch Med Wochenschr 137:1297–1300

    Article  CAS  PubMed  Google Scholar 

  14. Mital S, Chung WK, Colan SD, Sleeper LA, Manlhiot C, Arrington CB et al (2011) Renin-angiotensin-aldosterone genotype influences ventricular remodeling in infants with single ventricle. Circulation 123:2353–2362

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Myers GL, Miller WG, Coresh J, Fleming J, Greenberg N, Greene T et al (2006) Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program. Clin Chem 52:5–18

    Article  CAS  PubMed  Google Scholar 

  16. Packer M, Lee WH, Medina N, Yushak M, Kessler PD (1987) Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure. Ann Intern Med 106:346–354

    Article  CAS  PubMed  Google Scholar 

  17. Phelps CM, Eshelman J, Cruz ED, Pan Z, Kaufman J (2012) Acute kidney injury after cardiac surgery in infants and children: evaluation of the role of angiotensin-converting enzyme inhibitors. Pediatr Cardiol 33:1–7

    Article  PubMed  Google Scholar 

  18. Plotz FB, Bouma AB, van Wijk JA, Kneyber MC, Bokenkamp A (2008) Pediatric acute kidney injury in the ICU: an independent evaluation of pRIFLE criteria. Intensive Care Med 34:1713–1717

    Article  PubMed  Google Scholar 

  19. Price JF, Mott AR, Dickerson HA, Jefferies JL, Nelson DP, Chang AC et al (2008) Worsening renal function in children hospitalized with decompensated heart failure: evidence for a pediatric cardiorenal syndrome? Pediatr Crit Care Med 9:279–284

    Article  PubMed  Google Scholar 

  20. Saul JP, Ross B, Schaffer MS, Beerman L, Melikian AP, Shi J et al (2001) Pharmacokinetics and pharmacodynamics of sotalol in a pediatric population with supraventricular and ventricular tachyarrhythmia. Clin Pharmacol Ther 69:145–157

    Article  CAS  PubMed  Google Scholar 

  21. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263

    CAS  PubMed  Google Scholar 

  22. Sharkey I, Boddy AV, Wallace H, Mycroft J, Hollis R, Picton S (2001) Body surface area estimation in children using weight alone: application in paediatric oncology. Br J Cancer 85:23–28

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Shull BC, Haughey D, Koup JR, Baliah T, Li PK (1978) A useful method for predicting creatinine clearance in children. Clin Chem 24:1167–1169

    CAS  PubMed  Google Scholar 

  24. Tan LH, Du LZ, Carr MR, Kuzin JK, Moffett BS, Chang AC (2011) Captopril-induced reversible acute renal failure in a premature neonate with double-outlet right ventricle and congestive heart failure. World J Pediatr 7:89–91

    Article  CAS  PubMed  Google Scholar 

  25. Tufro-McReddie A, Gomez RA (1993) Ontogeny of the renin-angiotensin system. Semin Nephrol 13:519–530

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Lillie Frank Abercrombie Section of Pediatric Cardiology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA

    Katherine A. Lindle, W. Buck Kyle & Susan D. Denfield

  2. Department of Pharmacy, Texas Children’s Hospital, Houston, TX, USA

    Kim Dinh & Brady S. Moffett

  3. Department of Pharmacy, University of Mississippi Medical Center, Jackson, MS, USA

    Natalie M. Montgomery

  4. Division of Critical Care Medicine, Department of Pediatrics, University of Mississippi Medical Center, Children’s Healthcare of Mississippi, 2500 North State Street, Jackson, MS, 39216, USA

    Jarrod D. Knudson

Authors
  1. Katherine A. Lindle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kim Dinh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brady S. Moffett
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W. Buck Kyle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Natalie M. Montgomery
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Susan D. Denfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jarrod D. Knudson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jarrod D. Knudson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lindle, K.A., Dinh, K., Moffett, B.S. et al. Angiotensin-Converting Enzyme Inhibitor Nephrotoxicity in Neonates with Cardiac Disease. Pediatr Cardiol 35, 499–506 (2014). https://doi.org/10.1007/s00246-013-0813-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-013-0813-2

Keywords

Search

Navigation