Neonatal Acute Kidney Injury

  • Indrani Bhattacharjee
  • Marissa J. DeFreitas
  • Maroun Mhanna
  • Carolyn AbitbolEmail author


Neonatal acute kidney injury (nAKI) is highly prevalent but the definition of nAKI remains nebulous. This is because we rely on serum creatinine (SCr) for the estimation of kidney function which is an indirect measure of muscle mass and the maternal placental transfer of SCr in the early post-natal period. Similarly, the physiological transition into the extra-uterine environment should result in a natural improvement in neonatal renal function from 25% to at least 60% of adult renal function within the first post-natal week. This should lead to a natural and steady decline in the SCr from birth to discharge. Neonatal AKI may be defined as a rise in SCr of >0.3 mg/dL, a peak in SCr ≥1.5 mg/dL and/or a “nadir” SCr at discharge ≥0.5 mg/dL. Importantly, infants born preterm and/or small for gestational age are more vulnerable to nAKI. Diagnosis, early medical intervention and longterm follow-up are essential for these individuals to avert the likely progression to chronic kidney disease including hypertension and cardiorenal disease with shortened longevity.


Neonatal Acute kidney injury Nephrogenesis Prematurity Nephron endowment Postnatal adaptation Serum creatinine Estimated glomerular filtration rate 


  1. 1.
    Koralkar R, Ambalavanan N, Levitan EB, McGwin G, Goldstein S, Askenazi D. Acute kidney injury reduces survival in very low birth weight infants. Pediatr Res. 2011;69:354–8.CrossRefGoogle Scholar
  2. 2.
    Carmody JB, Swanson JR, Rhone ET, Charlton JR. Recognition and reporting of AKI in very low birth weight infants. Clin J Am Soc Nephrol. 2014;9:2036–43.CrossRefGoogle Scholar
  3. 3.
    Selewski DT, Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ, Kent AL. Neonatal acute kidney injury. Pediatrics. 2015;136(2):e463–73.CrossRefGoogle Scholar
  4. 4.
    Luyckx VA, Bertram LF, Brenner BM, Fall C, Hoy WE, Ozanne SE, Vikse BE. Effect of fetal and child health on kidney development and long-term risk of hypertension and kidney disease. Lancet. 2013;382(9888):273–83.CrossRefGoogle Scholar
  5. 5.
    Askenazi DJ, Morgan C, Goldstein SL, Selewski DT, Moxey-Mims MM, Kimmel PL, Star RA, Higgins R, Laughon M. Strategies to improve the understanding of long-term renal consequences after neonatal acute kidney injury. Pediatr Res. 2016;79(3):502–8.CrossRefGoogle Scholar
  6. 6.
    Zappitelli M, Ambalavanan N, Askenazi DJ, Moxey-Mims MM, Kimmel PL, Star RA, Abitbol CL, Brophy PD, Hidalgo G, Hanna M, Morgan CM, Raju TNK, Ray P, Reyes-Bou Z, Roushdi A, Goldstein SL. Developing a neonatal acute kidney injury research definition: a report from the NIDDK neonatal AKI workshop. Pediatr Res. 2017;82(4):569–73.CrossRefGoogle Scholar
  7. 7.
    Jetton JG, Guillet R, Askenazi DJ, Dill L, Jacobs J, Kent AL, Selewski DT, Abitbol CL, Kaskel FJ, Mhanna MJ, Ambalavanan N, Charlton JR, The Neonatal Kidney Collaborative. Assessment of worldwide acute kidney injury epidemiology in neonates: design of a retrospective cohort study. Front Pediatr. 2016;4:68.CrossRefGoogle Scholar
  8. 8.
    Jetton JG, Boohaker LJ, Sethi SK, Wazir S, Rohatgi S, Soranno D, Chishti AS, Woroniecki R, Mammen C, Swanson SR, Sridhar S, Wong CS, Kupferman JC, Griffin RL, Askenazi DJ, on behalf of the Neonatal Kidney Collaborative (NKC). Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study. Lancet Child Adolesc Health. 2017;1:184–94.CrossRefGoogle Scholar
  9. 9.
    Harer MW, Askenazi DJ, Boohaker LJ, Carmody JB, Griffin RL, Guillet R, Selewski DT, Swanson JR, Charlton JR, Neonatal Kidney Collaborative (NKC). Association between early caffeine citrate administration and risk of acute kidney injury in preterm neonates: results from the AWAKEN study. JAMA Pediatr. 2018;172:e180322. Scholar
  10. 10.
    Drukker A, Guignard J. Renal aspects of the term and preterm infant: a selective update. Curr Opin Pediatr. 2002;14:175–82.CrossRefGoogle Scholar
  11. 11.
    Rosenblum S, Pal A, Reidy K. Renal development in the fetus and premature infant. Semin Fetal Neonatal Med. 2017;22(2):58–66.CrossRefGoogle Scholar
  12. 12.
    Rodríguez MM, Gómez AH, Abitbol CL, Chandar JJ, Duara S, Zilleruelo GE. Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm infants. Pediatr Dev Pathol. 2004;7(1):17–25.CrossRefGoogle Scholar
  13. 13.
    Sutherland MR, Gubhaju L, Moore L, Kent AL, Dahlstrom JE, Horne RS, Hoy WE, Bertram JF, Black MJ. Accelerated maturation and abnormal morphology in the preterm neonatal kidney. J Am Soc Nephrol. 2011;22(7):1365–74.CrossRefGoogle Scholar
  14. 14.
    Choker G, Gouyon JB. Diagnosis of acute renal failure in very preterm infants. Biol Neonate. 2004;86:212–6.CrossRefGoogle Scholar
  15. 15.
    Nada A, Bonachea EM, Askenazi DJ. Acute kidney injury in the fetus and neonate. Semin Fetal Neonatal Med. 2017;22(2):90–7.CrossRefGoogle Scholar
  16. 16.
    Kastl JT. Renal function in the fetus and neonate – the creatinine enigma. Semin Fetal Neonatal Med. 2017;22(2):83–9.CrossRefGoogle Scholar
  17. 17.
    Mian AN, Schwartz GJ. Measurement and estimation of glomerular filtration rate in children. Adv Chronic Kidney Dis. 2017;24(6):348–56.CrossRefGoogle Scholar
  18. 18.
    Abitbol CL, DeFreitas MJ, Strauss J. Assessment of kidney function in preterm infants: lifelong implications. Pediatr Nephrol. 2016;31(12):2213–22.CrossRefGoogle Scholar
  19. 19.
    Treiber M, Pecovnik Balon B, Gorenjak M. A new serum cystatin C formula for estimating glomerular filtration rate in newborns. Pediatr Nephrol. 2015;30:1297–305.CrossRefGoogle Scholar
  20. 20.
    Bruel A, Rozé JC, Quere MP, Flamant C, Boivin M, Roussey-Kesler G, Allain-Launay E. Renal outcome in children born preterm with neonatal acute renal failure: IRENEO-a prospective controlled study. Pediatr Nephrol. 2016;31(12):2365–73.CrossRefGoogle Scholar
  21. 21.
    Abitbol CL, Bauer CR, Montané B, Chandar J, Duara S, Zilleruelo G. Long-term follow-up of extremely low birth weight infants with neonatal renal failure. Pediatr Nephrol. 2003;18(9):887–93.CrossRefGoogle Scholar
  22. 22.
    Weintraub AS, Connors J, Carey A, Blanco V, Green RS. The spectrum of onset of acute kidney injury in premature infants less than 30 weeks gestation. J Perinatol. 2016;36(6):474–80.CrossRefGoogle Scholar
  23. 23.
    Askenazi DJ, Koralkar R, Patil N, Halloran B, Ambalavanan N, Griffin R. Acute kidney injury urine biomarkers in very low-birth-weight infants. Clin J Am Soc Nephrol. 2016;11(9):1527–35.CrossRefGoogle Scholar
  24. 24.
    Tóth-Heyn P, Drukker A, Guignard JP. The stressed neonatal kidney: from pathophysiology to clinical management of neonatal vasomotor nephropathy. Pediatr Nephrol Berl Ger. 2000;14(3):227–39.CrossRefGoogle Scholar
  25. 25.
    Gouyon JB, Guignard JP. Vasomotor kidney failure in the newborn infant. Physiopathology and treatment. Arch Fr Pediatr. 1989;46(2):137–41.PubMedGoogle Scholar
  26. 26.
    Criss CN, Selewski DT, Sunkara B, Gish JS, Hsieh L, Mcleod JS, et al. Acute kidney injury in necrotizing enterocolitis predicts mortality. Pediatr Nephrol Berl Ger. 2018;33(3):503–10.CrossRefGoogle Scholar
  27. 27.
    Blinder JJ, Goldstein SL, Lee V-V, Baycroft A, Fraser CD, Nelson D, et al. Congenital heart surgery in infants: effects of acute kidney injury on outcomes. J Thorac Cardiovasc Surg. 2012;143(2):368–74.CrossRefGoogle Scholar
  28. 28.
    Polglase GR, Ong T, Hillman NH. Cardiovascular alterations and multiorgan dysfunction after birth asphyxia. Clin Perinatol. 2016;43(3):469–83.CrossRefGoogle Scholar
  29. 29.
    Jetton JG, Askenazi DJ. Acute kidney injury in the neonate. Clin Perinatol. 2014;41(3):487–502.CrossRefGoogle Scholar
  30. 30.
    Fanos V, Antonucci R, Zaffanello M, Mussap M. Neonatal drug induced nephrotoxicity: old and next generation biomarkers for early detection and management of neonatal drug-induced nephrotoxicity, with special emphasis on uNGAL and on metabolomics. Curr Med Chem. 2012;19(27):4595–605.CrossRefGoogle Scholar
  31. 31.
    Jetton JG, Sorenson M. Pharmacological management of acute kidney injury and chronic kidney disease in neonates. Semin Fetal Neonatal Med. 2017;22(2):109–15.CrossRefGoogle Scholar
  32. 32.
    Rees L. Renal replacement therapies in neonates: issues and ethics. Semin Fetal Neonatal Med. 2017;22(2):104–8.CrossRefGoogle Scholar
  33. 33.
    Askenazi D, Ingram D, White S, Koyner JL, Arthur JM, Shaw AD, et al. Smaller circuits for smaller patients: improving renal support therapy with Aquadex. Pediatr Nephrol. 2016;31:853e60.Google Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Indrani Bhattacharjee
    • 1
  • Marissa J. DeFreitas
    • 2
  • Maroun Mhanna
    • 3
  • Carolyn Abitbol
    • 4
    Email author
  1. 1.NeonatologyCase Western Reserve University, Neonatal Perinatal Medicine, MetroHealth Medical Center/Cleveland Clinic FoundationClevelandUSA
  2. 2.Clinical Pediatrics, Department of Pediatrics/Division of Pediatric NephrologyHoltz Children’s Hospital/Jackson Memorial HospitalMiamiUSA
  3. 3.PediatricsCase Western Reserve University, Pediatric Critical Care and Neonatal Perinatal Medicine, MetroHealth Medical CenterClevelandUSA
  4. 4.Pediatrics, Pediatric DialysisUniversity of Miami/Holtz Children’s HospitalMiamiUSA

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