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Serum and urine acute kidney injury biomarkers in asphyxiated neonates

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Abstract

Background

We evaluated serum (s) cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) and urine (u) CysC, NGAL and kidney injury molecule-1 (KIM-1) as markers of acute kidney injury (AKI) in asphyxiated neonates.

Methods

AKI biomarkers were measured in 13 asphyxiated neonates born at ≥36 weeks gestational age (eight with AKI and five without AKI) and 22 controls. AKI was defined as serum creatinine ≥1.5 mg/dl for >24 h or rising values >0.3 mg/dl from day of life (DOL) 1. Biomarkers were measured on DOL 1, 3, and 10.

Results

Asphyxiated neonates had significantly higher sCysC on DOL 1 as well as sNGAL and uCysC and uNGAL (standardized to urine creatinine and absolute values) than controls at all time points. Compared to controls, significantly higher sNGAL, uCysC, and uNGAL values were observed in the asphyxia-AKI and asphyxia–no AKI subgroups. Regarding uKIM-1, only the absolute values were significantly higher in asphyxiated neonates (DOL 10). sNGAL, uCyst, and uNGAL had a significant diagnostic performance as predictors AKI on DOL 1.

Conclusions

sNGAL, uCysC, and uNGAL are sensitive, early AKI biomarkers, increasing significantly in asphyxiated neonates even in those not fulfilling AKI criteria. Their measurement on DOL 1 is predictive of post-asphyxia-AKI.

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References

  1. Shah P, Riphagen S, Beyene J, Perlman M (2004) Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 89:F152–155

    Article  PubMed  CAS  Google Scholar 

  2. Gupta BD, Sharma P, Bagla J, Parakh M, Soni JP (2005) Renal failure in asphyxiated neonates. Indian Pediatr 42:928–934

    PubMed  CAS  Google Scholar 

  3. Perlman JM, Tack ED (1988) Renal injury in the asphyxiated newborn infant: relationship to neurologic outcome. J Pediatr 113:875–879

    Article  PubMed  CAS  Google Scholar 

  4. 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  Google Scholar 

  5. Jenik AG, Ceriani Cernadas JM, Gorenstein A, Ramirez JA, Vain N, Armadans M, Ferraris JR (2000) A randomized, double-blind, placebo-controlled trial of the effects of prophylactic theophylline on renal function in term neonates with perinatal asphyxia. Pediatrics 105:E45

    Article  PubMed  CAS  Google Scholar 

  6. Bagshaw SM, Bellomo R (2010) Cystatin C in acute kidney injury. Curr Opin Crit Care. doi:10.1097/MCC.0b013e32833e8412

  7. Ahlström A, Tallgren M, Peltonen S, Pettilä V (2004) Evolution and predictive power of serum cystatin C in acute renal failure. Clin Nephrol 62:344–350

    PubMed  Google Scholar 

  8. Herget-Rosenthal S, Marggraf G, Hüsing J, Göring F, Pietruck F, Janssen O, Philipp T, Kribben A (2004) Early detection of acute renal failure by serum cystatin C. Kidney Int 66:1115–1122

    Article  PubMed  CAS  Google Scholar 

  9. Herrero-Morín JD, Málaga S, Fernández N, Rey C, Diéguez MA, Solís G, Concha A, Medina A (2007) Cystatin C and beta2-microglobulin: markers of glomerular filtration in critically ill children. Crit Care 11:R59

    Article  PubMed  Google Scholar 

  10. Nejat M, Pickering JW, Walker RJ, Endre ZH (2010) Rapid detection of acute kidney injury by plasma cystatin C in the intensive care unit. Nephrol Dial Transplant 25:3283–3289

    Article  PubMed  CAS  Google Scholar 

  11. Herget-Rosenthal S, van Wijk JA, Bröcker-Preuss M, Bökenkamp A (2007) Increased urinary cystatin C reflects structural and functional renal tubular impairment independent of glomerular filtration rate. Clin Biochem 40:946–951

    Article  PubMed  CAS  Google Scholar 

  12. Nejat M, Pickering JW, Walker RJ, Westhuyzen J, Shaw GM, Frampton CM, Endre ZH (2010) Urinary cystatin C is diagnostic of acute kidney injury and sepsis, and predicts mortality in the intensive care unit. Crit Care 14:R85

    Article  PubMed  Google Scholar 

  13. Koyner JL, Bennett MR, Worcester EM, Ma Q, Raman J, Jeevanandam V, Kasza KE, O'Connor MF, Konczal DJ, Trevino S, Devarajan P, Murray PT (2008) Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery. Kidney Int 74:1059–1069

    Article  PubMed  CAS  Google Scholar 

  14. Malyszko J, Bachorzewska-Gajewska H, Poniatowski B, Malyszko JS, Dobrzycki S (2009) Urinary and serum biomarkers after cardiac catheterization in diabetic patients with stable angina and without severe chronic kidney disease. Ren Fail 31:910–919

    Article  PubMed  CAS  Google Scholar 

  15. 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  PubMed  CAS  Google Scholar 

  16. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238

    Article  PubMed  CAS  Google Scholar 

  17. Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, Lee HT (2006) Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology 105:485–491

    Article  PubMed  CAS  Google Scholar 

  18. Haase-Fielitz A, Bellomo R, Devarajan P, Story D, Matalanis G, Dragun D, Haase M (2009) Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery–a prospective cohort study. Crit Care Med 37:553–560

    Article  PubMed  CAS  Google Scholar 

  19. Parikh CR, Devarajan P, Zappitelli M, Sint K, Thiessen-Philbrook H, Li S, Kim RW, Koyner JL, Coca SG, Edelstein CL, Shlipak MG, Garg AX, Krawczeski CD, TRIBE-AKI Consortium (2011) Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol 22:1737–1747

    Article  PubMed  CAS  Google Scholar 

  20. Hall IE, Yarlagadda SG, Coca SG, Wang Z, Doshi M, Devarajan P, Han WK, Marcus RJ, Parikh CR (2010) IL-18 and urinary NGAL predict dialysis and graft recovery after kidney transplantation. J Am Soc Nephrol 21:189–197

    Article  PubMed  CAS  Google Scholar 

  21. Bagshaw SM, Bennett M, Haase M, Haase-Fielitz A, Egi M, Morimatsu H, D'amico G, Goldsmith D, Devarajan P, Bellomo R (2010) Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness. Intensive Care Med 36:452–461

    Article  PubMed  CAS  Google Scholar 

  22. Ichimura T, Hung CC, Yang SA, Stevens JL, Bonventre JV (2004) Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol Renal Physiol 286:F552–563

    Article  PubMed  CAS  Google Scholar 

  23. Han WK, Waikar SS, Johnson A, Betensky RA, Dent CL, Devarajan P, Bonventre JV (2008) Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int 73:863–869

    Article  PubMed  CAS  Google Scholar 

  24. Koyner JL, Vaidya VS, Bennett MR, Ma Q, Worcester E, Akhter SA, Raman J, Jeevanandam V, O'Connor MF, Devarajan P, Bonventre JV, Murray PT (2010) Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury. Clin J Am Soc Nephrol 5:2154–2165

    Article  PubMed  CAS  Google Scholar 

  25. Finney H, Newman DJ, Thakkar H, Fell JM, Price CP (2000) Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children. Arch Dis Child 82:71–75

    Article  PubMed  CAS  Google Scholar 

  26. Askenazi DJ, Koralkar R, Levitan EB, Goldstein SL, Devarajan P, Khandrika S, Mehta RL, Ambalavanan N (2011) Baseline values of candidate urine acute kidney injury biomarkers vary by gestational age in premature infants. Pediatr Res 70:302–306

    Article  PubMed  Google Scholar 

  27. 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  PubMed  CAS  Google Scholar 

  28. Krawczeski CD, Woo JG, Wang Y, Bennett MR, Ma Q, Devarajan P (2011) Neutrophil gelatinase-associated lipocalin concentrations predict development of acute kidney injury in neonates and children after cardiopulmonary bypass. J Pediatr 158:1009–1015.e1

    Article  PubMed  CAS  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 159:907–12.e1

    Article  PubMed  CAS  Google Scholar 

  30. Sarnat HB, Sarnat MS (1976) Neonatal encephalopathy following fetal distress: a clinical and electroencephalographic study. Arch Neurol 33:695–706

    Google Scholar 

  31. Chaturvedi S, Farmer T, Kapke GF (2009) Assay validation for KIM-1: human urinary renal dysfunction biomarker. Int J Biol Sci 5:128–134

    Article  PubMed  CAS  Google Scholar 

  32. Cataldi L, Mussap M, Bertelli L, Ruzzante N, Fanos V, Plebani M (1999) 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 16:287–295

    Article  PubMed  CAS  Google Scholar 

  33. O'Connell AE, Boyce AC, Lumbers ER, Gibson KJ (2003) The effects of asphyxia on renal function in fetal sheep at midgestation. J Physiol 552:933–943

    Article  PubMed  Google Scholar 

  34. Ikeda T, Murata Y, Quilligan EJ, Parer JT, Murayama T, Koono M (2000) Histologic and biochemical study of the brain, heart, kidney, and liver in asphyxia caused by occlusion of the umbilical cord in near-term fetal lambs. Am J Obstet Gynecol 182:449–457

    Article  PubMed  CAS  Google Scholar 

  35. Willis F, Summers J, Minutillo C, Hewitt I (1997) Indices of renal tubular function in perinatal asphyxia. Arch Dis Child Fetal Neonatal Ed 77:F57–60

    Article  PubMed  CAS  Google Scholar 

  36. Roberts DS, Haycock GB, Dalton RN, Turner C, Tomlinson P, Stimmler L, Scopes JW (1990) Prediction of acute renal failure after birth asphyxia. Arch Dis Child 65:1021–1028

    Article  PubMed  CAS  Google Scholar 

  37. Zappitelli M, Washburn KK, Arikan AA, Loftis L, Ma Q, Devarajan P, Parikh CR, Goldstein SL (2007) Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Crit Care 11:R84

    Article  PubMed  Google Scholar 

  38. Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A, NGAL Meta-analysis Investigator Group (2009) Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis 54:1012–1024

    Article  PubMed  CAS  Google Scholar 

  39. Jang HR, Rabb H (2009) The innate immune response in ischemic acute kidney injury. Clin Immunol 130:41–50

    Article  PubMed  CAS  Google Scholar 

  40. El-Achkar TM, Hosein M, Dagher PC (2008) Pathways of renal injury in systemic gram-negative sepsis. Eur J Clin Invest 38:39–44

    Article  PubMed  CAS  Google Scholar 

  41. Hoffmann D, Fuchs TC, Henzler T, Matheis KA, Herget T, Dekant W, Hewitt P, Mally A (2010) Evaluation of a urinary kidney biomarker panel in rat models of acute and subchronic nephrotoxicity. Toxicology 277:49–58

    Article  PubMed  CAS  Google Scholar 

  42. Nykjaer A, Schambye H, Pedersen AH, Nielsen H (2009) Assessing low-dose gentamicin-induced kidney injury in rats by analysis of urine. J Pharmacol Toxicol Meth 60:316–320

    Article  CAS  Google Scholar 

  43. Waikar SS, Sabbisetti VS, Bonventre JV (2010) Normalization of urinary biomarkers to creatinine during changes in glomerular filtration rate. Kidney Int 78:486–494

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Kosmas Sarafidis.

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Sarafidis, K., Tsepkentzi, E., Agakidou, E. et al. Serum and urine acute kidney injury biomarkers in asphyxiated neonates. Pediatr Nephrol 27, 1575–1582 (2012). https://doi.org/10.1007/s00467-012-2162-4

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  • DOI: https://doi.org/10.1007/s00467-012-2162-4

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