Pediatric Nephrology

, Volume 28, Issue 3, pp 477–484 | Cite as

Serum cystatin C predicts acute kidney injury in preterm neonates with respiratory distress syndrome

  • Ahmet Taner Elmas
  • Yilmaz Tabel
  • Özlem Nalbantoğlu Elmas
Original Article



We aimed to compare serum cystatin C levels (sCysC) in preterm neonates with respiratory distress syndrome (RDS) with a control group and to investigate whether it could be used as a predictor for acute kidney injury (AKI).


sCysC was measured in 62 neonates with RDS (n = 28) and control neonates without RDS (n = 34), whose gestational ages (GA) were between 27 and 29 weeks (subgroup 1) and 30–32 weeks (subgroup 2). AKI was defined as oliguria and/or increase of serum creatinine. Blood samples were obtained on postnatal days (PND) 3 and 30. sCysC levels were determined by particle-enhanced nephelometric immunoassay.


There were six neonates with AKI (RDS-AKI subgroup) and 22 neonates without AKI (RDS-no AKI subgroup) during the first 7 days. Although sCysC levels were lower in neonates with RDS than controls on PND3 in both GA subgroups, the differences were not significant. However, in neonates with RDS and AKI, sCysC levels were significantly higher than neonates with RDS but no AKI and neonates in the control group on PND3. sCysC level was found to have a statistically significant association with AKI development in preterm neonates with RDS.


sCysC is an independent predictor of AKI in preterm neonates with RDS.


Preterm Neonates Respiratory distress syndrome Acute kidney injury Serum cystatin C 


  1. 1.
    Roberts D, Dalziel S (2006) Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 3:CD004454PubMedGoogle Scholar
  2. 2.
    Lemons JA, Bauer CR, Oh W, Korones SB, Papile LA, Stoll BJ, Verter J, Temprosa M, Wright LL, Ehrenkranz RA, Fanaroff AA, Stark A, Carlo W, Tyson JE, Donovan EF, Shankaran S, Stevenson DK (2001) Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 through December 1996. NICHD neonatal research network. Pediatrics 107:E1PubMedCrossRefGoogle Scholar
  3. 3.
    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 69:354–358PubMedCrossRefGoogle Scholar
  4. 4.
    Askenazi DJ, Griffin R, McGwin G, Carlo W, Ambalavanan N (2009) Acute kidney injury is independently associated with mortality in very low birth weight infants: a matched case–control analysis. Pediatr Nephrol 24:991–997PubMedCrossRefGoogle Scholar
  5. 5.
    Andreoli SP (2004) Acute renal failure in the newborn. Semin Perinatol 28:112–123PubMedCrossRefGoogle Scholar
  6. 6.
    Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A (2007) Acute Kidney Injury Network (AKIN): report of an initiative to improve outcomes in acute kidney injury. Crit Care 11:R31PubMedCrossRefGoogle Scholar
  7. 7.
    Hoste EA, Kellum JA (2006) RIFLE criteria provide robust assessment of kidney dysfunction and correlate with hospital mortality. Crit Care Med 34:2016–2017PubMedCrossRefGoogle Scholar
  8. 8.
    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 24:265–274PubMedCrossRefGoogle Scholar
  9. 9.
    Gallini F, Maggio L, Romagnoli C, Marrocco G, Tortorolo G (2000) Progression of renal function in preterm neonates with gestational age < or = 32 weeks. Pediatr Nephrol 15:119–124PubMedCrossRefGoogle Scholar
  10. 10.
    Brion LP, Fleischman AR, McCarton C, Schwartz GJ (1986) A simple estimate of glomerular filtration rate in low birth weight infants during the first year of life: noninvasive assessment of body composition and growth. J Pediatr 109:698–707PubMedCrossRefGoogle Scholar
  11. 11.
    Parikh CR, Lu JC, Coca SG, Devarajan P (2010) Tubular proteinuria in acute kidney injury: a critical evaluation of current status and future promise. Ann Clin Biochem 47:301–312PubMedCrossRefGoogle Scholar
  12. 12.
    Devarajan P (2008) The future of pediatric acute kidney injury management–biomarkers. Semin Nephrol 28:493–498PubMedCrossRefGoogle Scholar
  13. 13.
    Bagshaw SM, Bellomo R (2007) Early diagnosis of acute kidney injury. Curr Opin Crit Care 13:638–644PubMedCrossRefGoogle Scholar
  14. 14.
    Filler G, Bökenkamp A, Hofmann W, Le Bricon T, Martínez-Brú C, Grubb A (2005) Cystatin C as a marker of GFR-history, indications, and future research. Clin Biochem 38:1–8PubMedCrossRefGoogle Scholar
  15. 15.
    Sharma AP, Kathiravelu A, Nadarajah R, Yasin A, Filler G (2009) Body mass does not have a clinically relevant effect on cystatin C eGFR in children. Nephrol Dial Transplant 24:470–474PubMedCrossRefGoogle Scholar
  16. 16.
    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 16:287–295PubMedCrossRefGoogle Scholar
  17. 17.
    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:R59PubMedCrossRefGoogle Scholar
  18. 18.
    Krawczeski CD, Vandevoorde RG, Kathman T, Bennett MR, Woo JG, Wang Y, Griffiths RE, Devarajan P (2010) Serum cystatin C is an early predictive biomarker of acute kidney injury after pediatric cardiopulmonary bypass. Clin J Am Soc Nephrol 5:1552–1557PubMedCrossRefGoogle Scholar
  19. 19.
    Ahlström A, Tallgren M, Peltonen S, Pettilä V (2004) Evolution and predictive power of serum cystatin C in acute renal failure. Clin Nephrol 62:344–350PubMedGoogle Scholar
  20. 20.
    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 66:1115–1122PubMedCrossRefGoogle Scholar
  21. 21.
    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 25:3283–3289PubMedCrossRefGoogle Scholar
  22. 22.
    Finney H, Newman DJ, Gruber W, Merle P, Price CP (1997) Initial evaluation of cystatin C measurement by particle-enhanced immunonephelometry on the Behring nephelometer systems (BNA, BN II). Clin Chem 43:1016–1022PubMedGoogle Scholar
  23. 23.
    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 71:1028–1035PubMedCrossRefGoogle Scholar
  24. 24.
    Langlois V (2008) Laboratory evaluation at different ages. In: Geary D, Shaefer F (eds) Comprehensive pediatric nephrology, 1st edn. Mosby Elsevier, Philadelphia, pp 39–54CrossRefGoogle Scholar
  25. 25.
    Hentschel R, Lodige B, Bulla M (1996) Renal insufficiency in the neonatal period. Clin Nephrol 46:54–58PubMedGoogle Scholar
  26. 26.
    Cataldi L, Leone R, Moretti U, De Mitri B, Fanos V, Ruggeri L, Sabatino G, Torcasio F, Zanardo V, Attardo G, Riccobene F, Martano C, Benini D, Cuzzolin L (2005) Potential risk factors for the development of acute renal failure in preterm newborn infants: a case–control study. Arch Dis Child Fetal Neonatal Ed 90:F514–F519PubMedCrossRefGoogle Scholar
  27. 27.
    Vasarhelyi B, Toth-Heyn P, Treszl A, Tulassay T (2005) Genetic polymorphisms and risk for acute renal failure in preterm neonates. Pediatr Nephrol 20:132–135PubMedCrossRefGoogle Scholar
  28. 28.
    Rodriguez-Soriano J, Aguirre M, Oliveros R, Vallo A (2005) Long-term renal follow-up of extremely low birth weight infants. Pediatr Nephrol 20:579–584PubMedCrossRefGoogle Scholar
  29. 29.
    Mortazavi F, Hosseinpour Sakha S, Nejati N (2009) Acute kidney failure in neonatal period. Iran J Kidney Dis 3:136–140PubMedGoogle Scholar
  30. 30.
    Li Y, Fu C, Zhou X, Xiao Z, Zhu X, Jin M, Li X, Feng X (2012) Urine interleukin-18 and cystatin-C as biomarkers of acute kidney injury in critically ill neonates. Pediatr Nephrol 27:851–860PubMedCrossRefGoogle Scholar
  31. 31.
    Karlowicz MG, Adelman RD (1995) Nonoliguric and oliguric acute renal failure in asphyxiated term neonates. Pediatr Nephrol 9:718–722PubMedCrossRefGoogle Scholar
  32. 32.
    Cuzzolin L, Fanos V, Pinna B, di Marzio M, Perin M, Tramontozzi P, Tonetto P, Cataldi L (2006) Postnatal renal function in preterm newborns: a role of diseases, drugs and therapeutic interventions. Pediatr Nephrol 21:931–938PubMedCrossRefGoogle Scholar
  33. 33.
    Tulassay T, Vasarhelyi B (2002) Birth weight and renal function. Curr Opin Nephrol Hypertens 11:347–352PubMedCrossRefGoogle Scholar
  34. 34.
    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 82:71–75PubMedCrossRefGoogle Scholar
  35. 35.
    Bariciak E, Yasin A, Harrold J, Walker M, Lepage N, Filler G (2011) Preliminary reference intervals for cystatin C and beta-trace protein in preterm and term neonates. Clin Biochem 44:1156–1159PubMedCrossRefGoogle Scholar
  36. 36.
    Bartelink IH, Rademaker CM, Schobben AF, van den Anker JN (2006) Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations. Clin Pharmacokinet 45:1077–1097PubMedCrossRefGoogle Scholar
  37. 37.
    Filler G, Browne R, Seikaly MG (2003) Glomerular filtration rate as a putative ‘surrogate end-point’ for renal transplant clinical trials in children. Pediatr Transplant 7:18–24PubMedCrossRefGoogle Scholar
  38. 38.
    Roos JF, Doust J, Tett SE, Kirkpatrick CM (2007) Diagnostic accuracy of cystatin C compared to serum creatinine for the estimation of renal dysfunction in adults and children-a meta-analysis. Clin Biochem 40:383–391PubMedCrossRefGoogle Scholar
  39. 39.
    Bagshaw SM, Bellomo R (2010) Cystatin C in acute kidney injury. Curr Opin Crit Care. doi:10.1097/MCC.0b013e32833e8412
  40. 40.
    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 37:553–560PubMedCrossRefGoogle Scholar
  41. 41.
    Sarafidis K, Tsepkentzi E, Agakidou E, Diamanti E, Taparkou A, Soubasi V, Papachristou F, Drossou V (2012) Serum and urine acute kidney injury biomarkers in asphyxiated neonates. Pediatr Nephrol 27:1575–1582PubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2012

Authors and Affiliations

  • Ahmet Taner Elmas
    • 1
  • Yilmaz Tabel
    • 1
    • 3
  • Özlem Nalbantoğlu Elmas
    • 2
  1. 1.Department of Pediatric Nephrology, Faculty of MedicineUniversity of InonuMalatyaTurkey
  2. 2.Department of PediatricsState HospitalMalatyaTurkey
  3. 3.Inonu Universitesi, Turgut Ozal Tip MerkeziMalatyaTurkey

Personalised recommendations