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A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy

Pediatric Nephrology volume 31, pages 1167–1178 (2016)Cite this article

Abstract

Background

Current definitions of acute kidney injury (AKI) are not sufficiently sensitive to identify all newborns with AKI during the first week of life.

Methods

To determine whether the rate of decline of serum creatinine (SCr) during the first week of life can be used to identify newborns with AKI, we reviewed the medical records of 106 term neonates at risk of AKI who were treated with hypothermia for hypoxic ischemic encephalopathy (HIE).

Results

Of the newborns enrolled in the study, 69 % showed a normal rate of decline of SCr to ≥50 % and/or reached SCr levels of ≤0.6 mg/dl before the 7th day of life, and therefore had an excellent clinical outcome (control group). Thirteen newborns with HIE (12 %) developed AKI according to an established neonatal definition (AKI–KIDGO group), and an additional 20 newborns (19 %) showed a rate of decline of SCr of <33, <40, and <46 % from birth to days 3, 5, or 7 of life, respectively (delayed rise in estimated SCr clearance group). Compared to the control group, newborns in the other two groups required more days of mechanical ventilation and vasopressor drugs and had higher gentamicin levels, more fluid overload, lower urinary epidermal growth factor levels, and a prolonged length of stay.

Conclusions

The rate of decline of SCr provides a sensitive approach to identify term newborns with AKI during the first week of life.

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References

  1. Shankaran S (2014) Outcomes of hypoxic-ischemic encephalopathy in neonates treated with hypothermia. Clin Perinatol 41:149–159

    Article  PubMed  Google Scholar 

  2. Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH, National Institute of Child H Human Development Neonatal Research N (2005) Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 353:1574–1584

    Article  CAS  PubMed  Google Scholar 

  3. Shankaran S, Laptook AR, McDonald SA, Higgins RD, Tyson JE, Ehrenkranz RA, Das A, Sant’Anna G, Goldberg RN, Bara R, Walsh MC, Eunice Kennedy Shriver National Institute of Child H, Human Development Neonatal Research Network (2012) Temperature profile and outcomes of neonates undergoing whole body hypothermia for neonatal hypoxic-ischemic encephalopathy. Pediatr Crit Care Med 13:53–59

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sarkar S, Askenazi DJ, Jordan BK, Bhagat I, Bapuraj JR, Dechert RE, Selewski DT (2014) Relationship between acute kidney injury and brain MRI findings in asphyxiated newborns after therapeutic hypothermia. Pediatr Res 75:431–435

    Article  PubMed  Google Scholar 

  5. Selewski DT, Jordan BK, Askenazi DJ, Dechert RE, Sarkar S (2013) Acute kidney injury in asphyxiated newborns treated with therapeutic hypothermia. J Pediatr 162(725–729):e721

    Google Scholar 

  6. Thomas ME, Blaine C, Dawnay A, Devonald MA, Ftouh S, Laing C, Latchem S, Lewington A, Milford DV, Ostermann M (2015) The definition of acute kidney injury and its use in practice. Kidney Int 87:62–73

    Article  PubMed  Google Scholar 

  7. Askenazi DJ, Ambalavanan N, Goldstein SL (2009) Acute kidney injury in critically ill newborns: what do we know? What do we need to learn? Pediatr Nephrol 24:265–274

    Article  PubMed  PubMed Central  Google Scholar 

  8. Drukker A, Guignard JP (2002) Renal aspects of the term and preterm infant: a selective update. Curr Opin Pediatr 14:175–182

    Article  PubMed  Google Scholar 

  9. Karlowicz MG, Adelman RD (1995) Nonoliguric and oliguric acute renal failure in asphyxiated term neonates. Pediatr Nephrol 9:718–722

    Article  CAS  PubMed  Google Scholar 

  10. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A, Acute Kidney Injury N (2007) Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11:R31

    Article  PubMed  PubMed Central  Google Scholar 

  11. 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 

  12. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group (2012) KDIGO clinical practice guidelines for acute kidney injury. Section 2: AKIdefinition. Kidney Int Suppl 2:19–36

    Article  Google Scholar 

  13. Schwartz GJ, Furth SL (2007) Glomerular filtration rate measurement and estimation in chronic kidney disease. Pediatr Nephrol 22:1839–1848

    Article  PubMed  Google Scholar 

  14. Schwartz GJ, Feld LG, Langford DJ (1984) A simple estimate of glomerular filtration rate in full-term infants during the first year of life. J Pediatr 104:849–854

    Article  CAS  PubMed  Google Scholar 

  15. Schwartz GJ, Brion LP, Spitzer A (1987) The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 34:571–590

    CAS  PubMed  Google Scholar 

  16. Jetton JG, Askenazi DJ (2012) Update on acute kidney injury in the neonate. Curr Opin Pediatr 24:191–196

    Article  CAS  PubMed  Google Scholar 

  17. Selewski DT, Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ, Kent AL (2015) Neonatal acute kidney injury. Pediatrics 136:e463–e473

    Article  PubMed  Google Scholar 

  18. Singbartl K, Kellum JA (2012) AKI in the ICU: definition, epidemiology, risk stratification, and outcomes. Kidney Int 81:819–825

    Article  CAS  PubMed  Google Scholar 

  19. Alinei P, Guignard JP (1987) Assessment of glomerular filtration rate in infants. Comparison of three methods used in clinical practice. Helv Paediatr Acta 42:253–262

    CAS  PubMed  Google Scholar 

  20. Guignard JP, Torrado A, Feldman H, Gautier E (1980) Assessment of glomerular filtration rate in children. Helv Paediatr Acta 35:437–447

    CAS  PubMed  Google Scholar 

  21. Barnett HL, Hare WK, McNamara H, Hare RS (1948) Influence of postnatal age on kidney function of premature infants. Proc Soc Exp Biol Med 69:55–57

  22. Leake RD, Trygstad CW, Oh W (1976) Inulin clearance in the newborn infant: relationship to gestational and postnatal age. Pediatr Res 10:759–762

    CAS  PubMed  Google Scholar 

  23. Sertel H, Scopes J (1973) Rates of creatinine clearance in babies less than one week of age. Arch Dis Child 48:717–720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Aperia A, Broberger O, Elinder G, Herin P, Zetterstrom R (1981) Postnatal development of renal function in pre-term and full-term infants. Acta Paediatr Scand 70:183–187

    Article  CAS  PubMed  Google Scholar 

  25. Feldman H, Guignard JP (1982) Plasma creatinine in the first month of life. Arch Dis Child 57:123–126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hoffman SB, Massaro AN, Soler-Garcia AA, Perazzo S, Ray PE (2013) A novel urinary biomarker profile to identify acute kidney injury (AKI) in critically ill neonates: a pilot study. Pediatr Nephrol 28:2179–2188

    Article  PubMed  PubMed Central  Google Scholar 

  27. 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 9:2036–2043

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wai K, Soler-Garcia AA, Perazzo S, Mattison P, Ray PE (2013) A pilot study of urinary fibroblast growth factor-2 and epithelial growth factor as potential biomarkers of acute kidney injury in critically ill children. Pediatr Nephrol 28:2189–2198

    Article  PubMed  PubMed Central  Google Scholar 

  29. Askenazi DJ, Montesanti A, Hunley H, Koralkar R, Pawar P, Shuaib F, Liwo A, Devarajan P, Ambalavanan N (2011) Urine biomarkers predict acute kidney injury and mortality in very low birth weight infants. J Pediatr 159(907–912):e901

    Google Scholar 

  30. Grund B, Sabin C (2010) Analysis of biomarker data: logs, odds ratios, and receiver operating characteristic curves. Curr Opin HIV AIDS 5:473–479

    Article  PubMed  PubMed Central  Google Scholar 

  31. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW (2005) Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 16:3365–3370

    Article  PubMed  Google Scholar 

  32. Zappitelli M, Bernier PL, Saczkowski RS, Tchervenkov CI, Gottesman R, Dancea A, Hyder A, Alkandari O (2009) A small post-operative rise in serum creatinine predicts acute kidney injury in children undergoing cardiac surgery. Kidney Int 76:885–892

    Article  CAS  PubMed  Google Scholar 

  33. Pottel H, Vrydags N, Mahieu B, Vandewynckele E, Croes K, Martens F (2008) Establishing age/sex related serum creatinine reference intervals from hospital laboratory data based on different statistical methods. Clin Chim Acta 396:49–55

    Article  CAS  PubMed  Google Scholar 

  34. Paragas N, Qiu A, Zhang Q, Samstein B, Deng SX, Schmidt-Ott KM, Viltard M, Yu W, Forster CS, Gong G, Liu Y, Kulkarni R, Mori K, Kalandadze A, Ratner AJ, Devarajan P, Landry DW, D’Agati V, Lin CS, Barasch J (2011) The Ngal reporter mouse detects the response of the kidney to injury in real time. Nat Med 17:216–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P (2003) Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 14:2534–2543

    Article  CAS  PubMed  Google Scholar 

  36. Wheeler DS, Devarajan P, Ma Q, Harmon K, Monaco M, Cvijanovich N, Wong HR (2008) Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock. Crit Care Med 36:1297–1303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lavery AP, Meinzen-Derr JK, Anderson E, Ma Q, Bennett MR, Devarajan P, Schibler KR (2008) Urinary NGAL in premature infants. Pediatr Res 64:423–428

    Article  CAS  PubMed  Google Scholar 

  38. Parravicini E (2010) The clinical utility of urinary neutrophil gelatinase-associated lipocalin in the neonatal ICU. Curr Opin Pediatr 22:146–150

    Article  PubMed  Google Scholar 

  39. Parravicini E, Nemerofsky SL, Michelson KA, Huynh TK, Sise ME, Bateman DA, Lorenz JM, Barasch JM (2010) Urinary neutrophil gelatinase-associated lipocalin is a promising biomarker for late onset culture-positive sepsis in very low birth weight infants. Pediatr Res 67:636–640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Chen L, Liu W (1997) Effect of asphyxia on urinary epidermal growth factor levels in newborns. J Tongji Med Univ 17:144–146

    Article  CAS  PubMed  Google Scholar 

  41. Boer DP, de Rijke YB, Hop WC, Cransberg K, Dorresteijn EM (2010) Reference values for serum creatinine in children younger than 1 year of age. Pediatr Nephrol 25:2107–2113

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank Sofia Perazzo for assistance in data analysis and presentation and Glenn M. Chertow for helpful discussions. This study was supported by National Institutes of Health (NIH) awards R0-1 HL-102497, R01-DK 49419, and U54HD071601.

Author information

Authors and Affiliations

  1. Division of Nephrology, Children’s National Health System, Washington, DC, USA

    Charu Gupta & Patricio E. Ray

  2. Division of Neonatology, Children’s National Health System, Washington, DC, USA

    An N. Massaro

  3. Center for Genetic Medicine Research, Children National Health System, Washington, DC, USA

    Patricio E. Ray

  4. Department of Pediatrics, The George Washington University School of Medicine–Children’s National Medical Center, 111 Michigan Avenue, NW, Washington, DC, 20010, USA

    An N. Massaro & Patricio E. Ray

Authors
  1. Charu Gupta
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  2. An N. Massaro
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Corresponding author

Correspondence to Patricio E. Ray.

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Conflict of interest

The authors declare no conflict of interest.

Ethics statement

This Institutional Review Board at Children’s National Health System approved the study protocol in adherence to the Declaration of Helsinki and waived the need for consent.

Electronic supplementary material

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Supplemental Table S1

Serum Creatinine values in newborns with HIE during the first week of life (DOC 47 kb)

Supplemental Table S2

ROC curves for SCr and SCr decline combined. Samples from Controls and AKI-KDIGO + DReCrCl groups combined (n = 106) (DOC 12 kb)

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Gupta, C., Massaro, A.N. & Ray, P. A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy. Pediatr Nephrol 31, 1167–1178 (2016). https://doi.org/10.1007/s00467-016-3317-5

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  • DOI: https://doi.org/10.1007/s00467-016-3317-5

Keywords

  • Neonate
  • Acute kidney injury
  • Biomarkers
  • Serum creatinine
  • Epidermal growth factor