Skip to main content
PMC home page
Archives of Disease in Childhood logoLink to Archives of Disease in Childhood
. 2000 Jan;82(1):71–75. doi: 10.1136/adc.82.1.71

Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children

H Finney 1, D Newman 1, H Thakkar 1, J Fell 1, C Price 1
PMCID: PMC1718178  PMID: 10630919

Abstract

AIM—To establish a reference range in the paediatric population for the new glomerular filtration rate (GFR) marker, cystatin C, and to compare it with that of creatinine.
METHODS—Cystatin C and creatinine were measured by particle enhanced nephelometric immunoassay (PENIA) and fixed interval Jaffé methods, respectively, in 291 children aged 1 day to 17 years, including 30 premature infants with gestational ages ranging from 24 to 36weeks.
RESULTS—In the premature infants, concentrations of both cystatin C and creatinine were significantly raised compared with term infants, with cystatin C concentrations being between 1.10 and 2.06 mg/litre and creatinine between 32 and 135 µmol/litre. In premature infants, there was no significant relation between gestational age and cystatin C or creatinine concentration. Creatinine concentrations fell to a nadir at 4 months of age, rising gradually to adult values by about 15-17 years of age, in contrast to cystatin C, which fell to a mean concentration of 0.80 mg/litre by the 1st year of life, and remained constant throughout adulthood up to the age of 50 years. Neither analyte showed any influence of sex.
CONCLUSION—The measurement of cystatin C, rather than creatinine, is more practical for monitoring GFR changes in the paediatric population.


Full Text

The Full Text of this article is available as a PDF (163.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aperia A., Broberger O., Elinder G., Herin P., Zetterström R. Postnatal development of renal function in pre-term and full-term infants. Acta Paediatr Scand. 1981 Mar;70(2):183–187. doi: 10.1111/j.1651-2227.1981.tb05539.x. [DOI] [PubMed] [Google Scholar]
  2. Brion L. P., Fleischman A. R., McCarton C., Schwartz G. J. 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. 1986 Oct;109(4):698–707. doi: 10.1016/s0022-3476(86)80245-1. [DOI] [PubMed] [Google Scholar]
  3. Burritt M. F., Slockbower J. M., Forsman R. W., Offord K. P., Bergstralh E. J., Smithson W. A. Pediatric reference intervals for 19 biologic variables in healthy children. Mayo Clin Proc. 1990 Mar;65(3):329–336. doi: 10.1016/s0025-6196(12)62533-6. [DOI] [PubMed] [Google Scholar]
  4. Bökenkamp A., Domanetzki M., Zinck R., Schumann G., Brodehl J. Reference values for cystatin C serum concentrations in children. Pediatr Nephrol. 1998 Feb;12(2):125–129. doi: 10.1007/s004670050419. [DOI] [PubMed] [Google Scholar]
  5. Bökenkamp A., Domanetzki M., Zinck R., Schumann G., Byrd D., Brodehl J. Cystatin C--a new marker of glomerular filtration rate in children independent of age and height. Pediatrics. 1998 May;101(5):875–881. doi: 10.1542/peds.101.5.875. [DOI] [PubMed] [Google Scholar]
  6. Chantler C. The measurement of renal function in children: a review. Guys Hosp Rep. 1973;122(1-2):25–41. [PubMed] [Google Scholar]
  7. Cherian A. G., Hill J. G. Percentile estimates of reference values for fourteen chemical constituents in sera of children and adolescents. Am J Clin Pathol. 1978 Jan;69(1):24–31. doi: 10.1093/ajcp/69.1.24. [DOI] [PubMed] [Google Scholar]
  8. Donckerwolcke R. A., Sander P. C., van Stekelenburg G. J., Stoop J. W., Tiddens H. A. Serum creatinine values in healthy children. Acta Paediatr Scand. 1970 Jul;59(4):399–402. doi: 10.1111/j.1651-2227.1970.tb15534.x. [DOI] [PubMed] [Google Scholar]
  9. Emmrich P., Baumann W., Stechele U. Studies on the kinetics and renal excretion of low and high molecular weight dextrans in preterm babies, newborns and young infants. Eur J Pediatr. 1977 Jul 1;125(3):181–190. doi: 10.1007/BF00480595. [DOI] [PubMed] [Google Scholar]
  10. Fawer C. L., Torrado A., Guignard J. P. Maturation of renal function in full-term and premature neonates. Helv Paediatr Acta. 1979 Feb;34(1):11–21. [PubMed] [Google Scholar]
  11. Feldman H., Guignard J. P. Plasma creatinine in the first month of life. Arch Dis Child. 1982 Feb;57(2):123–126. doi: 10.1136/adc.57.2.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fell J. M., Thakkar H., Newman D. J., Price C. P. Measurement of albumin and low molecular weight proteins in the urine of newborn infants using a cotton wool ball collection method. Acta Paediatr. 1997 May;86(5):518–522. doi: 10.1111/j.1651-2227.1997.tb08923.x. [DOI] [PubMed] [Google Scholar]
  13. Filler G., Witt I., Priem F., Ehrich J. H., Jung K. Are cystatin C and beta 2-microglobulin better markers than serum creatinine for prediction of a normal glomerular filtration rate in pediatric subjects? Clin Chem. 1997 Jun;43(6 Pt 1):1077–1078. [PubMed] [Google Scholar]
  14. Finney H., Newman D. J., Gruber W., Merle P., Price C. P. Initial evaluation of cystatin C measurement by particle-enhanced immunonephelometry on the Behring nephelometer systems (BNA, BN II). Clin Chem. 1997 Jun;43(6 Pt 1):1016–1022. [PubMed] [Google Scholar]
  15. Gordjani N., Burghard R., Leititis J. U., Brandis M. Serum creatinine and creatinine clearance in healthy neonates and prematures during the first 10 days of life. Eur J Pediatr. 1988 Nov;148(2):143–145. doi: 10.1007/BF00445923. [DOI] [PubMed] [Google Scholar]
  16. Grubb A. Diagnostic value of analysis of cystatin C and protein HC in biological fluids. Clin Nephrol. 1992;38 (Suppl 1):S20–S27. [PubMed] [Google Scholar]
  17. Grubb A., Simonsen O., Sturfelt G., Truedsson L., Thysell H. Serum concentration of cystatin C, factor D and beta 2-microglobulin as a measure of glomerular filtration rate. Acta Med Scand. 1985;218(5):499–503. doi: 10.1111/j.0954-6820.1985.tb08880.x. [DOI] [PubMed] [Google Scholar]
  18. Kyhse-Andersen J., Schmidt C., Nordin G., Andersson B., Nilsson-Ehle P., Lindström V., Grubb A. Serum cystatin C, determined by a rapid, automated particle-enhanced turbidimetric method, is a better marker than serum creatinine for glomerular filtration rate. Clin Chem. 1994 Oct;40(10):1921–1926. [PubMed] [Google Scholar]
  19. Laskarzewski P., Kelly K. A., Mellies M. J., Morrison J. A., Khoury P., Tillett S., Glueck C. J. Clinical chemistry determinations for a biracial cohort of 1,605 normal and hyperlipidemic schoolchildren aged 6 to 17. Am J Clin Pathol. 1980 Oct;74(4):371–380. doi: 10.1093/ajcp/74.4.371. [DOI] [PubMed] [Google Scholar]
  20. Newman D. J., Thakkar H., Edwards R. G., Wilkie M., White T., Grubb A. O., Price C. P. Serum cystatin C measured by automated immunoassay: a more sensitive marker of changes in GFR than serum creatinine. Kidney Int. 1995 Jan;47(1):312–318. doi: 10.1038/ki.1995.40. [DOI] [PubMed] [Google Scholar]
  21. Norlund L., Fex G., Lanke J., Von Schenck H., Nilsson J. E., Leksell H., Grubb A. Reference intervals for the glomerular filtration rate and cell-proliferation markers: serum cystatin C and serum beta 2-microglobulin/cystatin C-ratio. Scand J Clin Lab Invest. 1997 Oct;57(6):463–470. doi: 10.3109/00365519709084595. [DOI] [PubMed] [Google Scholar]
  22. Piepsz A., Pintelon H., Ham H. R. Estimation of normal chromium-51 ethylene diamine tetra-acetic acid clearance in children. Eur J Nucl Med. 1994 Jan;21(1):12–16. doi: 10.1007/BF00182300. [DOI] [PubMed] [Google Scholar]
  23. SCHULZ D. M., GIORDANO D. A., SCHULZ D. H. Weights of organs of fetuses and infants. Arch Pathol. 1962 Sep;74:244–250. [PubMed] [Google Scholar]
  24. Savory D. J. Reference ranges for serum creatinine in infants, children and adolescents. Ann Clin Biochem. 1990 Mar;27(Pt 2):99–101. doi: 10.1177/000456329002700201. [DOI] [PubMed] [Google Scholar]
  25. Schwartz G. J., Brion L. P., Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am. 1987 Jun;34(3):571–590. doi: 10.1016/s0031-3955(16)36251-4. [DOI] [PubMed] [Google Scholar]
  26. Schwartz G. J., Feld L. G., Langford D. J. A simple estimate of glomerular filtration rate in full-term infants during the first year of life. J Pediatr. 1984 Jun;104(6):849–854. doi: 10.1016/s0022-3476(84)80479-5. [DOI] [PubMed] [Google Scholar]
  27. Schwartz G. J., Haycock G. B., Spitzer A. Plasma creatinine and urea concentration in children: normal values for age and sex. J Pediatr. 1976 May;88(5):828–830. doi: 10.1016/s0022-3476(76)81125-0. [DOI] [PubMed] [Google Scholar]
  28. Simonsen O., Grubb A., Thysell H. The blood serum concentration of cystatin C (gamma-trace) as a measure of the glomerular filtration rate. Scand J Clin Lab Invest. 1985 Apr;45(2):97–101. doi: 10.3109/00365518509160980. [DOI] [PubMed] [Google Scholar]
  29. Sonntag J., Prankel B., Waltz S. Serum creatinine concentration, urinary creatinine excretion and creatinine clearance during the first 9 weeks in preterm infants with a birth weight below 1500 g. Eur J Pediatr. 1996 Sep;155(9):815–819. doi: 10.1007/BF02002914. [DOI] [PubMed] [Google Scholar]
  30. van den Anker J. N., de Groot R., Broerse H. M., Sauer P. J., van der Heijden B. J., Hop W. C., Lindemans J. Assessment of glomerular filtration rate in preterm infants by serum creatinine: comparison with inulin clearance. Pediatrics. 1995 Dec;96(6):1156–1158. [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood are provided here courtesy of BMJ Publishing Group

RESOURCES