Cystatin C in newborns: a promising renal biomarker in search for standardization and validation

J Matern Fetal Neonatal Med. 2015;28(15):1833-8. doi: 10.3109/14767058.2014.969236. Epub 2014 Nov 5.


Objective: Neonatologists still commonly use creatinine as a proxy for renal clearance, despite issues related to neonatal (patho)physiology and methodology (assay variability). Cystatin C (CysC) has been suggested to be a more reliable biomarker, but assay related differences have also been reported in children and adults. We are unaware of any review on the assay related impact on CysC reference values in newborns.

Methods: A structured literature search was performed on published CysC values in (pre)term neonates.

Results: The extensive range (>5-fold) in serum CysC observations in neonates in part relates to the fact that CysC concentrations are higher at birth with subsequent decrease and that CysC concentrations are higher in preterm compared to term neonates. The CysC assay matters while disease characteristics also affect CysC values, but not always in the predicted direction.

Conclusions: Similar to creatinine, the extensive CysC range in neonates is only in part explained by renal (patho)physiology. Its applicability in neonatal medicine can be further improved by use of assay specific reference values, adapted to neonatal renal physiology (e.g. weight, age) and should be compared to a gold standard such as inulin clearance.

Keywords: Cystatin C; developmental nephrology; glomerular filtration rate; neonatal renal clearance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Biomarkers / blood*
  • Cystatin C / blood*
  • Female
  • Fetal Organ Maturity / physiology
  • Humans
  • Infant, Newborn / blood*
  • Kidney / embryology
  • Kidney / physiology
  • Kidney Function Tests / methods
  • Kidney Function Tests / standards*
  • Reference Standards
  • Reference Values
  • Validation Studies as Topic


  • Biomarkers
  • Cystatin C