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Diagnostic Biomarkers of Acute Kidney Injury in Newborns

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Biomarkers in Kidney Disease

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Abstract

Acute kidney injury refers to the rapid loss of renal function. In newborns, although the precise incidence of acute kidney injury is unknown, research has shown that 8–24 % of all critically ill newborns in neonatal intensive care units may develop the condition. Although traditional markers of acute kidney injury lack sensitivity and specificity for early diagnosis in the neonatal period, several novel serum and urinary biomarkers are under intense scrutiny for their role as noninvasive indicators of early acute kidney injury. The most promising biomarkers are cystatin C, neutrophil gelatinase-associated lipocalin, interleukin-18, and kidney injury molecule-1.

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Abbreviations

AKI:

Acute kidney injury

CysC:

Cystatin C

EGF:

Epidermal growth factor

FGF-2:

Fibroblast growth factor-2

GFR:

Glomerular filtration rate

IL-18:

Interleukin-18

KIM-1:

Kidney injury molecule-1

NGAL:

Neutrophil gelatinase-associated lipocalin

NICUs:

Neonatal intensive care units

sCysC:

Serum CysC

sNGAL:

Serum neutrophil gelatinase-associated lipocalin

uCysC:

Urinary CysC

uIL-18:

Urinary interleukin-18

uKIM-1:

Urine kidney injury molecule-1

uNGAL:

Urinary neutrophil gelatinase-associated lipocalin

References

  • Abitbol CL, Bauer CR, Montané B, et al. Long-term follow-up of extremely low birth weight infants with neonatal renal failure. Pediatr Nephrol. 2003;18:887–93.

    Article  PubMed  Google Scholar 

  • Agras PI, Tarcan A, Baskin E, et al. Acute renal failure in the neonatal period. Ren Fail. 2004;26:305–9.

    Article  PubMed  Google Scholar 

  • Akcan-Arikan A, Zappitelli M, Loftis LL, et al. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int. 2007;71:1028–35.

    Article  CAS  PubMed  Google Scholar 

  • Alge JL, Karakala N, Neely BA, SAKInet Investigators, et al. Urinary angiotensinogen and risk of severe AKI. Clin J Am Soc Nephrol. 2013a;8:184–93.

    Article  CAS  PubMed  Google Scholar 

  • Alge JL, Karakala N, Neely BA, SAKInet Investigators, et al. Urinary angiotensinogen predicts adverse outcomes among acute kidney injury patients in the intensive care unit. Crit Care. 2013b;17:R69.

    Article  PubMed  PubMed Central  Google Scholar 

  • Andreoli SP. Acute renal failure in the newborn. Semin Perinatol. 2004;28:112–23.

    Article  PubMed  Google Scholar 

  • Argyri I, Xanthos T, Varsami M, et al. The role of novel biomarkers in early diagnosis and prognosis of acute kidney injury in newborns. Am J Perinatol. 2013;30:347–52.

    Article  PubMed  Google Scholar 

  • Armangil D, Yurdakök M, Canpolat FE, et al. Determination of reference values for plasma cystatin C and comparison with creatinine in premature infants. Pediatr Nephrol. 2008;23:2081–3.

    Article  PubMed  Google Scholar 

  • Askenazi DJ, Ambalavanan N, Goldstein SL. Acute kidney injury in critically ill newborns: what do we know? What do we need to learn? Pediatr Nephrol. 2009a;24:265–74.

    Article  PubMed  Google Scholar 

  • Askenazi DJ, Griffin R, McGwin G, et al. Acute kidney injury is independently associated with mortality in very low birthweight infants: a matched case-control analysis. Pediatr Nephrol. 2009b;24:991–7.

    Article  PubMed  Google Scholar 

  • Askenazi DJ, Montesanti A, Hunley H, et al. Urine biomarkers predict acute kidney injury and mortality in very low birth weight infants. J Pediatr. 2011;159:907–12.

    Article  CAS  PubMed  Google Scholar 

  • Askenazi DJ, Koralkar R, Hundley HE, et al. Urine biomarkers predict acute kidney injury in newborns. J Pediatr. 2012;161:270–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Atzori L, Antonucci R, Barberini L, et al. 1H NMR-based metabolomic analysis of urine from preterm and term neonates. Front Biosci (Elite Ed). 2011;3:1005–12.

    Article  Google Scholar 

  • Bariciak E, Yasin A, Harrold J, et al. Preliminary reference intervals for cystatin C and beta-trace protein in preterm and term neonates. Clin Biochem. 2011;44:1156–9.

    Article  CAS  PubMed  Google Scholar 

  • Bender L, Thaarup J, Varming K, et al. Early and late markers for the detection of early-onset neonatal sepsis. Dan Med Bull. 2008;55:219–23.

    CAS  PubMed  Google Scholar 

  • Bolignano D, Donato V, Coppolino G, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis. 2008;52:595–605.

    Article  CAS  PubMed  Google Scholar 

  • Bonventre JV. Kidney injurymolecule-1 (KIM-1): a urinary biomarker and much more. Nephrol Dial Transplant. 2009;24:3265–8.

    Article  CAS  PubMed  Google Scholar 

  • Cataldi L, Mussap M, Bertelli L, et al. Cystatin C in healthy women at term pregnancy and in their infant newborns: relationship between maternal and neonatal serum levels and reference values. Am J Perinatol. 1999;16:287–95.

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Liu W. Effect of asphyxia on urinary epidermal growth factor levels in newborns. J Tongi Med Univ. 1997;17:144–6.

    Article  CAS  Google Scholar 

  • Cusumano V, Midiri A, Cusumano VV, et al. Interleukin-18 is an essential element in host resistance to experimental group B streptococcal disease in neonates. Infect Immun. 2004;72:295–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Di Paolo S, Gesualdo L, Stallone G, et al. Renal expression and urinary concentration of EGF and IL-6 in acutely dysfunctioning kidney transplanted patients. Nephrol Dial Transplant. 1997;12:2687–93.

    Article  PubMed  Google Scholar 

  • Dinarello CA, Novick D, Puren AJ, et al. Overview of interleukin-18: more than an interferon-γ inducing factor. J Leukoc Biol. 1998;63:658–64.

    CAS  PubMed  Google Scholar 

  • Drukker A, Guignard JP. Renal aspects of the term and preterm infant: a selective update. Curr Opin Pediatr. 2002;14:175–82.

    Article  PubMed  Google Scholar 

  • Durkan AM, Alexander RT. Acute kidney injury post neonatal asphyxia. J Pediatr. 2011;158:e29–33.

    Article  PubMed  Google Scholar 

  • Elmas AT, Tabel Y, Elmas ON. Serum cystatin C predicts acute kidney injury in preterm neonates with respiratory distress syndrome. Pediatr Nephrol. 2013;28:477–84.

    Article  PubMed  Google Scholar 

  • Evans NJ, Rutter N, Gregory H. Urinary excretion of epidermal growth factor in the newborn. Early Hum Dev. 1986;14:277–82.

    Article  CAS  PubMed  Google Scholar 

  • Fanos V, Noto A, Caboni P, et al. Urine metabolomic profiling in neonatal nephrology. Clin Biochem. 2014;47:708–10.

    Article  CAS  PubMed  Google Scholar 

  • Gokmen T, Erdeve O, Altug N, et al. Efficacy and safety of oral versus intravenous ibuprofen in very low birth weight preterm infants with patent ductus arteriosus. J Pediatr. 2011;158:549–54. e1.

    Article  CAS  PubMed  Google Scholar 

  • Gupta BD, Sharma P, Bagla J, et al. Renal failure in asphyxiated neonates. Indian Pediatr. 2005;42:928–34.

    CAS  PubMed  Google Scholar 

  • Han WK, Waikar SS, Johnson A, et al. Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int. 2008;73:863–9.

    Article  CAS  PubMed  Google Scholar 

  • Hoffman SB, Massaro AN, Soler-García AA, et al. A novel urinary biomarker profile to identify acute kidney injury (AKI) in critically ill neonates: a pilot study. Pediatr Nephrol. 2013;28:2179–88.

    Article  PubMed  PubMed Central  Google Scholar 

  • Koch AM, Dittrich S, Cesnjevar R, et al. Plasma neutrophil gelatinase-associated lipocalin measured in consecutive patients after congenital heart surgery using point-of-care technology. Interact Cardiovasc Thorac Surg. 2011;13:133–6.

    Article  PubMed  Google Scholar 

  • Koralkar R, Ambalavanan N, Levitan EB, et al. Acute kidney injury reduces survival in very low birth weight infants. Pediatr Res. 2011;69:354–8.

    Article  PubMed  Google Scholar 

  • Krawczeski CD, Vandevoorde RG, Kathman T, et al. Serum Cystatin C is an early predictive biomarker of acute kidney injury after pediatric cardiopulmonary bypass. Clin J Am Soc Nephrol. 2010;5:1552–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krawczeski CD, Woo JG, Wang Y, et al. Neutrophil gelatinase-associated lipocalin concentrations predict development of acute kidney injury in neonates and children after cardiopulmonary bypass. J Pediatr. 2011;158:1009–15. e1.

    Article  CAS  PubMed  Google Scholar 

  • Kwon O, Ahn K, Zhang B, et al. Simultaneous monitoring of multiple urinary cytokines may predict renal and patient outcome in ischemic AKI. Ren Fail. 2010;32:699–708.

    Article  CAS  PubMed  Google Scholar 

  • La Manna G, Galletti S, Capelli I, et al. Urinary neutrophil gelatinase-associated lipocalin at birth predicts early renal function in very low birth weight infants. Pediatr Res. 2011;70:379–83.

    Article  PubMed  Google Scholar 

  • Lee BS, Byun SY, Chung ML, et al. Effect of furosemide on ductal closure and renal function in indomethacin-treated preterm infants during the early neonatal period. Neonatology. 2010;98:191–9.

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Fu C, Zhou X, et al. Urine interleukin-18 and cystatin-C as biomarkers of acute kidney injury in critically ill neonates. Pediatr Nephrol. 2012;27:851–60.

    Article  PubMed  PubMed Central  Google Scholar 

  • Libório AB, Branco KM, Torres de Melo Bezerra C. Acute kidney injury in neonates: from urine output to new biomarkers. Biomed Res Int. 2014;2014:601568.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lindon JC, Holmes E, Bollard ME, et al. Metabonomics technologies and their applications in physiological monitoring, drug safety assessment and disease diagnosis. Biomarkers. 2004;9:1–31.

    Article  CAS  PubMed  Google Scholar 

  • Maruniak-Chudek I, Owsianka-Podleśny T, Wróblewska J, et al. Is serum cystatin C a better marker of kidney function than serum creatinine in septic newborns? Postepy Hig Med Dosw (Online). 2012;66:175–80.

    Article  Google Scholar 

  • McWilliam SJ, Antoine DJ, Turner M, et al. Urinary KIM-1 as a biomarker of aminoglycoside-induced nephrotoxicity in premature neonates. Pediatr Res. 2011;70:107.

    Article  Google Scholar 

  • Melnikov VY, Ecder T, Fantuzzi G, et al. Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure. J Clin Invest. 2001;107:1145–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Melnikov VY, Faubel S, Siegmund B, et al. Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice. J Clin Invest. 2002;110:1083–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mishra J, Ma Q, Prada A, et al. Identification of NGAL as a novel urine biomarker for ischemic injury. J Am Soc Nephrol. 2003;14:2534–43.

    Article  CAS  PubMed  Google Scholar 

  • Mishra J, Mori K, Ma Q, et al. Neutrophil gelatinase-associated lipocalin: a novel early urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol. 2004;24:307–15.

    Article  CAS  PubMed  Google Scholar 

  • Mishra J, Ma Q, Kelly C, et al. Kidney NGAL is a novel early marker of acute injury following transplantation. Pediatr Nephrol. 2006;21:856–63.

    Article  PubMed  Google Scholar 

  • Murray PT, Le Gall JR, Dos Reis Miranda D, et al. Physiologic endpoints (efficacy) for acute renal failure studies. Curr Opin Crit Care. 2002;8:519–25.

    Article  PubMed  Google Scholar 

  • Novo AC, Sadeck LS, Okay TS, et al. Longitudinal study of Cystatin C in healthy term newborns. Clinics (Sao Paulo). 2011;66:217–20.

    Article  Google Scholar 

  • Pan Z, Raftery D. Comparing and combining NMR spectroscopy and mass spectrometry in metabolomics. Anal Bioanal Chem. 2007;387:525–7.

    Article  CAS  PubMed  Google Scholar 

  • Parikh CR, Devarajan P. New biomarkers of acute kidney injury. Crit Care Med. 2008;36:S159–65.

    Article  CAS  PubMed  Google Scholar 

  • Parikh CR, Mishra J, Thiessen-Philbrook H, et al. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int. 2006;70:199–203.

    Article  CAS  PubMed  Google Scholar 

  • Parravicini E, Nemerofsky SL, Michelson KA, et al. Urinary neutrophil gelatinase-associated lipocalin is a promising biomarker for late onset culture-positive sepsis in very low birth weight infants. Pediatr Res. 2010;67:636–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parvex P, Combescure C, Rodriguez M, et al. Is Cystatin C a promising marker of renal function, at birth, in neonates prenatally diagnosed with congenital kidney abnormalities? Nephrol Dial Transplant. 2012;27:3477–82.

    Article  CAS  PubMed  Google Scholar 

  • Plebani M, Mussap M, Bertelli L, et al. Determination of blood cystatin C in pregnant women during labor and in their newborns. Pediatr Med Chir. 1997;19:325–9.

    CAS  PubMed  Google Scholar 

  • Ray PE, Liu XH, Xu L, et al. Basic fibroblast growth factor in HIV-associated hemolytic uremic syndrome. Pediatr Nephrol. 1999;13:586–93.

    Article  CAS  PubMed  Google Scholar 

  • Ray P, Acheson D, Chitrakar R, et al. Basic fibroblast growth factor among children with diarrhea-associated hemolytic uremic syndrome. J Am Soc Nephrol. 2002;13:699–707.

    CAS  PubMed  Google Scholar 

  • Ray PE, Tassi E, Liu XH, et al. Role of fibroblast growth factor-binding protein in the pathogenesis of HIV-associated hemolytic uremic syndrome. Am J Physiol Regul Integr Comp Physiol. 2006;290:R105–13.

    Article  CAS  PubMed  Google Scholar 

  • Sarafidis K, Tsepkentzi E, Agakidou E, et al. Serum and urine acute kidney injury biomarkers in asphyxiated neonates. Pediatr Nephrol. 2012;27:1575–82.

    Article  PubMed  Google Scholar 

  • Sharma AP, Kathiravelu A, Nadarajah R, et al. Body mass does not have a clinically relevant effect on cystatin C eGFR in children. Nephrol Dial Transplant. 2009;24:470–4.

    Article  CAS  PubMed  Google Scholar 

  • Siew ED, Deger SM. Recent advances in acute kidney injury epidemiology. Curr Opin Nephrol Hypertens. 2012;21:309–17.

    Article  PubMed  PubMed Central  Google Scholar 

  • Singbartl K, Kellum JA. AKI in the ICU: definition, epidemiology, risk stratification, and outcomes. Kidney Int. 2012;81:819–25.

    Article  CAS  PubMed  Google Scholar 

  • Soler-Garcia AA, Rakhmanina NY, Mattison PC, et al. A urinary biomarker profile for children with HIV-associated renal diseases. Kidney Int. 2009;76:207–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tadesse S, Luo G, Park JS, et al. Intra-amniotic infection upregulates neutrophil gelatinase-associated lipocalin (NGAL) expression at the maternal-fetal interface at term: implications for infection related preterm birth. Reprod Sci. 2011;18:713–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Treiber M, Pecovnik-Balon B, Gorenjak M. Cystatin C versus creatinine as a marker of glomerular filtration rate in the newborn. Wien Klin Wochenschr. 2006;118:66–70.

    Article  CAS  PubMed  Google Scholar 

  • Tsau YK, Sheu JN, Chen CH, et al. Decreased urinary epidermal growth factor in children with acute renal failure: epidermal growth factor/creatinine ratio not a reliable parameter for urinary epidermal growth factor excretion. Pediatr Res. 1996;39:20–4.

    Article  CAS  PubMed  Google Scholar 

  • Vaidya VS, Ramirez V, Ichimura T, et al. Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol. 2006;290:F517–29.

    Article  CAS  PubMed  Google Scholar 

  • Wasilewska A, Zoch-Zwierz W, Taranta-Janusz K, et al. Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of cyclosporine nephrotoxicity? Pediatr Nephrol. 2010;25:889–97.

    Article  PubMed  Google Scholar 

  • Watanabe K, Ono A, Hirata Y, et al. Maturational changes and origin of urinary human epidermal growth factor in the neonatal period. Biol Neonate. 1989;56:241–5.

    Article  CAS  PubMed  Google Scholar 

  • Weiss RH, Kim K. Metabolomics in the study of kidney diseases. Nat Rev Nephrol. 2012;8:22–33.

    Article  CAS  Google Scholar 

  • Westhuyzen J. Cystatin C: a promising marker and predictor of impaired renal function. Ann Clin Lab Sci. 2006;36:387–94.

    CAS  PubMed  Google Scholar 

  • Zappitelli M, Parikh CR, Akcan-Arikan A, et al. Ascertainment and epidemiology of acute kidney injury varies with definition interpretation. Clin J Am Soc Nephrol. 2008;3:948–54.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou Y, Vaidya VS, Brown RP, et al. Comparison of kidney injury molecule-1 and other nephrotoxicity biomarkers in urine and kidney following acute exposure to gentamicin, mercury, and chromium. Toxicol Sci. 2008;101:159–70.

    Article  CAS  PubMed  Google Scholar 

  • Zwiers AJ, de Wildt SN, Hop WC, et al. Acute kidney injury is a frequent complication in critically ill neonates on extracorporeal membrane oxygenation: a 14-year cohort study. Crit Care. 2013;17:R151.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. University of Athens, Medical School, MSc “Cardiopulmonary Resuscitation”, 3 Ir. Politechniou Av., 18532, Piraeus, Greece

    Athanasios Chalkias

  2. Hellenic Society of Cardiopulmonary Resuscitation, 89 Patision Av., 10434, Athens, Greece

    Athanasios Chalkias & Nicoletta Iacovidou

  3. University of Athens, Medical School, Aretaieio Hospital, Department of Neonatology, 76 Vasilissis Sofias, 11528, Athens, Greece

    Nicoletta Iacovidou

Authors
  1. Athanasios Chalkias
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  2. Nicoletta Iacovidou
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Correspondence to Athanasios Chalkias .

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Editors and Affiliations

  1. DeptofBiomedlSci,FacltyofSci&Technology, University of Westminster , London, United Kingdom

    Vinood B. Patel

  2. Department of Nutrition and Dietetics,Division of Diabetes and Nutritional Sciences, Faculty of Life Science and Medicine, King’s College London, London, United Kingdom

    Victor R. Preedy

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Chalkias, A., Iacovidou, N. (2016). Diagnostic Biomarkers of Acute Kidney Injury in Newborns. In: Patel, V., Preedy, V. (eds) Biomarkers in Kidney Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7699-9_5

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