Patent ductus arteriosus is associated with acute kidney injury in the preterm infant

  • Batoule Majed
  • David A. BatemanEmail author
  • Natalie Uy
  • Fangming LinEmail author
Original Article



This study aimed to test the hypothesis that a patent ductus arteriosus (PDA) is independently associated with acute kidney injury (AKI) in neonates ≤ 28 weeks gestation.


Preterm infants with echocardiographic diagnosis of moderate-large PDA at age ≤ 30 days were studied retrospectively. AKI, the primary outcome, was defined and staged according to serum creatinine using Kidney Disease Improving Global Outcomes (KDIGO) neonatal criteria. Its association with the timing and duration of PDA, non-steroidal anti-inflammatory drugs (NSAIDs) and other nephrotoxic exposures, gestational age, and other covariates was evaluated using mixed-effects logistic regression models.


Acute Kidney Injury occurred in 49% (101/206) of infants. Moderate-to-large PDA was associated with any-stage AKI (OR 5.31, 95% CI 3.75 to 7.53), stage 1 (mild) AKI (OR 4.86, 95% CI 3.12 to 7.56), and stages 2–3 (severe) AKI (OR 10.9, 95% CI 5.70 to 20.8). NSAID treatment added additional risk for mild AKI (OR 2.45, 95% CI 1.61 to 3.71). Severe AKI was less likely when NSAID treatment was effective (OR 0.45, 95% CI 0.21 to 0.97) but not when ineffective (OR 1.63, 95% CI 0.76 to 3.50).


Moderate-to-large PDA was strongly associated with all stages of AKI in preterm infants ≤ 28 weeks of gestational age. Effective NSAID treatment decreased the risk of severe but not mild AKI. These differential effects reflect the balance between the renal benefits of PDA closure and the risk of NSAID toxicity.


Patent ductus arteriosus Acute kidney injury Non-steroidal anti-inflammatory drug 



Patent ductus arteriosus


Ductus arteriosus


Non-steroidal anti-inflammatory drug


Acute kidney injury


Kidney Disease Improving Global Outcomes


Serum creatinine


Gestational age



We wish to thank New York Presbyterian Hospital for supporting fellows’ education and research.

Compliance with ethical standards

The hospital institutional review board approved the study protocol and waived the need for consent.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Benitz WE, Committee on Fetus and Newborn, American Academy of Pediatrics (2016) Patent ductus arteriosus in preterm infants. Pediatrics 137:1–6CrossRefGoogle Scholar
  2. 2.
    Antonucci R, Fanos V (2009) NSAIDs, prostaglandins and the neonatal kidney. J Matern Fetal Neonatal Med 22(Suppl 3):23–26CrossRefGoogle Scholar
  3. 3.
    Selewski DT, Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ, Kent AL (2015) Neonatal acute kidney injury. Pediatrics 136:e463–e473CrossRefGoogle Scholar
  4. 4.
    Nada A, Bonachea EM, Askenazi DJ (2017) Acute kidney injury in the fetus and neonate. Semin Fetal Neonatal Med 22:90–97CrossRefGoogle Scholar
  5. 5.
    Van Overmeire B, Van de Broek H, Van Laer P, Weyler J, Vanhaesebrouck P (2001) Early versus late indomethacin treatment for patent ductus arteriosus in premature infants with respiratory distress syndrome. J Pediatr 138:205–211CrossRefGoogle Scholar
  6. 6.
    Ohlsson A, Walia R, Shah SS (2015) Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants. Cochrane Database Syst Rev 9:CD003481Google Scholar
  7. 7.
    Vanpee M, Ergander U, Herin P, Aperia A (1993) Renal function in sick, very low-birth-weight infants. Acta Paediatr 82:714–718CrossRefGoogle Scholar
  8. 8.
    Iacobelli S, Bonsante F, Ferdinus C, Labenne M, Gouyon J (2008) Factors affecting postnatal changes in serum creatinine in preterm infants with gestational age <32 weeks. J Perinatol 29:232–236CrossRefGoogle Scholar
  9. 9.
    Carmody JB, Swanson JR, Rhone ET, Charlton JR (2014) Recognition and reporting of AKI in very low birth weight infants. Clin J Am Soc Nephrol 9:2036–2043CrossRefGoogle Scholar
  10. 10.
    Koralkar R, Ambalavanan N, Levitan EB, McGwin G, Goldstein S, Askenazi D (2011) Acute kidney injury reduces survival in very low birth weight infants. Pediatr Res 69:354–358CrossRefGoogle Scholar
  11. 11.
    Rhone ET, Carmody JB, Swanson JR, Charlton JR (2014) Nephrotoxic medication exposure in very low birth weight infants. J Matern Fetal Neonatal Med 27:1485–1490CrossRefGoogle Scholar
  12. 12.
    Stojanovic V, Barisic N, Milanovic B, Doronjski A (2014) Acute kidney injury in preterm infants admitted to a neonatal intensive care unit. Pediatr Nephrol 29:2213–2220CrossRefGoogle Scholar
  13. 13.
    Weintraub AS, Connors J, Carey A, Blanco V, Green RS (2016) The spectrum of onset of acute kidney injury in premature infants less than 30 weeks gestation. J Perinatol 36:474–480CrossRefGoogle Scholar
  14. 14.
    Guignard JP, Drukker A (1999) Why do newborn infants have a high plasma creatinine? Pediatrics 103:e49CrossRefGoogle Scholar
  15. 15.
    Bateman DA, Thomas W, Parravicini E, Polesana E, Locatelli C, Lorenz JM (2015) Serum creatinine concentration in very-low-birth-weight infants from birth to 34-36 wk postmenstrual age. Pediatr Res 77:696–702CrossRefGoogle Scholar
  16. 16.
    Askenazi D, Patil NR, Ambalavanan N, Balena-Borneman J, Lozano DJ, Ramani M, Collins M, Griffin RL (2015) Acute kidney injury is associated with bronchopulmonary dysplasia/mortality in premature infants. Pediatr Nephrol 30:1511–1518CrossRefGoogle Scholar
  17. 17.
    Askenazi DJ, Griffin R, McGwin G, Carlo W, Ambalavanan N (2009) Acute kidney injury is independently associated with mortality in very low birthweight infants: a matched case-control analysis. Pediatr Nephrol 24:991–997CrossRefGoogle Scholar
  18. 18.
    Nemerofsky SL, Parravicini E, Bateman D, Kleinman C, Polin RA, Lorenz JM (2008) The ductus arteriosus rarely requires treatment in infants > 1000 grams. Am J Perinatol 25:661–666CrossRefGoogle Scholar
  19. 19.
    Vermont Oxford Network (2017) 2018 Manual of operations, part 2: data definitions & infant data forms. Vermont Oxford Network, Burlington, VTGoogle Scholar
  20. 20.
    Parry G, Tucker J, Tarnow-Mordi W, UK Neonatal Staffing Study Collaborative Group (2003) CRIB II: an update of the clinical risk index for babies score. Lancet 361:1789–1791CrossRefGoogle Scholar
  21. 21.
    Neu J (1996) Necrotizing enterocolitis: the search for a unifying pathogenic theory leading to prevention. Pediatr Clin N Am 43:409–432CrossRefGoogle Scholar
  22. 22.
    Akima S, Kent A, Reynolds GJ, Gallagher M, Falk MC (2004) Indomethacin and renal impairment in neonates. Pediatr Nephrol 19:490–493CrossRefGoogle Scholar
  23. 23.
    Itabashi K, Ohno T, Nishida H (2003) Indomethacin responsiveness of patent ductus arteriosus and renal abnormalities in preterm infants treated with indomethacin. J Pediatr 143:203–207CrossRefGoogle Scholar
  24. 24.
    Srinivasjois RM, Nathan EA, Doherty DA, Patole SK (2006) Renal impairment associated with indomethacin treatment for patent ductus arteriosus in extremely preterm neonates—is postnatal age at start of treatment important? J Matern Fetal Neonatal Med 19:793–799CrossRefGoogle Scholar
  25. 25.
    Antonucci R, Cuzzolin L, Arceri A, Dessi A, Fanos V (2009) Changes in urinary PGE2 after ibuprofen treatment in preterm infants with patent ductus arteriosus. Eur J Clin Pharmacol 65:223–230CrossRefGoogle Scholar
  26. 26.
    Allegaert K, Vanhole C, de Hoon J, Guignard JP, Tibboel D, Devlieger H, Van Overmeire B (2005) Nonselective cyclo-oxygenase inhibitors and glomerular filtration rate in preterm neonates. Pediatr Nephrol 20:1557–1561CrossRefGoogle Scholar
  27. 27.
    Noori S, McCoy M, Friedlich P, Bright B, Gottipati V, Seri I, Sekar K (2009) Failure of ductus arteriosus closure is associated with increased mortality in preterm infants. Pediatrics 123:e138–e144CrossRefGoogle Scholar

Copyright information

© IPNA 2019

Authors and Affiliations

  1. 1.Department of Pediatrics, Division of Pediatric Nephrology, New York Presbyterian Morgan Stanley Children’s HospitalColumbia University Medical CenterNew YorkUSA
  2. 2.Department of Pediatrics, Division of Neonatology, New York Presbyterian Morgan Stanley Children’s HospitalColumbia University Medical CenterNew YorkUSA

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