Skip to main content


Log in

New standardized cystatin C and creatinine GFR equations in children validated with inulin clearance

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript



This study compares glomerular filtration rate (GFR) equations in children based on standardized cystatin C (CYSC) and creatinine (CREA) and their combinations with renal clearance of inulin (C-inulin).


A total of 220 children with different renal disorders were referred for C-inulin (median 84 ml/min/1.73 m2). Bias, precision (interquartile range, IQR), and accuracy (percentage of estimates ±30 % of C-inulin; P30) were evaluated for two cystatin C equations, CAPACYSC and BergCYSC, for creatinine equations, SchwartzCREA and GaoCREA, the arithmetic mean of CAPACYSC and SchwartzCREA (MEANCAPA+Schwartz), BergCYSC and SchwartzCREA (MEANBERG+SCHWARTZ) and the composite equation ChehadeCYSC+CREA.


Overall results of CAPACYSC, BergCYSC, SchwartzCREA, GaoCREA, MEANCAPA+Schwartz, MEANBERG+SCHWARTZ and ChehadeCYSC+CREA were: median bias –7.6/–4.9/–3.7/–2.3/–4.6/–4.0/–10.1 %, IQR 20.0/19.9/21.7/22.4/21.0/20.9/23.3 ml/min/1.73 m2 and P30 86/86/80/83/89/91/83 %. The cystatin C equations, MEANCAPA+Schwartz and MEANBERG+SCHWARTZ had a more stable performance across subgroups compared with SchwartzCREA, GaoCREA and ChehadeCYSC+CREA.


Cystatin C was the preferred filtration marker for GFR estimation in children, while the benefit of combining cystatin C and creatinine deserves further investigations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others


  1. Smith HT (1951) The reliability of inulin as a measure of glomerular filtration rate. The Kidney: structure and function in health and disease. Oxford University Press, New York, NY, pp 231–238

    Google Scholar 

  2. Schwartz GJ, Work DF (2009) Measurement and estimation of GFR in children and adolescents. Clin J Am Soc Nephrol 4:1832–1843

    Article  PubMed  Google Scholar 

  3. Filler G, Lepage N (2003) Should the Schwartz formula for estimation of GFR be replaced by cystatin C formula? Pediatr Nephrol 18:981–985

    Article  PubMed  Google Scholar 

  4. Grubb A, Nyman U, Björk J, Lindström V, Rippe B, Sterner G, Christensson A (2005) Simple cystatin C-based prediction equations for glomerular filtration rate compared with the modification of diet in renal disease prediction equation for adults and the Schwartz and the Counahan-Barratt prediction equations for children. Clin Chem 51:1420–1431

    Article  CAS  PubMed  Google Scholar 

  5. Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637

    Article  PubMed Central  PubMed  Google Scholar 

  6. Gao A, Cachat F, Faouzi M, Bardy D, Mosig D, Meyrat BJ, Girardin E, Chehade H (2013) Comparison of the glomerular filtration rate in children by the new revised Schwartz formula and a new generalized formula. Kidney Int 83:524–530

    Article  CAS  PubMed  Google Scholar 

  7. Blirup-Jensen S, Grubb A, Lindström V, Schmidt C, Althaus H (2008) Standardization of Cystatin C: development of primary and secondary reference preparations. Scand J Clin Lab Invest Suppl 241:67–70

    Article  CAS  PubMed  Google Scholar 

  8. Grubb A, Blirup-Jensen S, Lindström V, Schmidt C, Althaus H, Zegers I, C IWGoSoC (2010) First certified reference material for cystatin C in human serum ERM-DA471/IFCC. Clin Chem Lab Med : CCLM / FESCC 48:1619–1621

    Article  CAS  Google Scholar 

  9. Grubb A, Horio M, Hansson LO, Björk J, Nyman U, Flodin M, Larsson A, Bökenkamp A, Yasuda Y, Blufpand H, Lindström V, Zegers I, Althaus H, Blirup-Jensen S, Itoh Y, Sjöström P, Nordin G, Christensson A, Klima H, Sunde K, Hjort-Christensen P, Armbruster D, Ferrero C (2014) Generation of a new cystatin C-based estimating equation for glomerular filtration rate by use of 7 assays standardized to the international calibrator. Clin Chem 60:974–986

  10. Chehade H, Cachat F, Jannot AS, Meyrat BJ, Mosig D, Bardy D, Parvex P, Girardin E (2014) New combined serum creatinine and cystatin C quadratic formula for GFR assessment in children. Clin J Am Soc Nephrol 9:54–63

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Berg U (1981) Renal function in acute febrile urinary tract infection in children: pathophysiologic aspects on the reduced concentrating capacity. Kidney Int 20:753–758

    Article  CAS  PubMed  Google Scholar 

  12. Kuehnle HF, von Dahl K, Schmidt FH (1992) Fully enzymatic inulin determination in small volume samples without deproteinization. Nephron 62:104–107

    Article  CAS  PubMed  Google Scholar 

  13. Haycock GB, Schwartz GJ, Wisotsky DH (1978) Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults. J Pediatr 93:62–66

    Article  CAS  PubMed  Google Scholar 

  14. Björk J, Bäck SE, Sterner G, Carlson J, Lindström V, Bakoush O, Simonsson P, Grubb A, Nyman U (2007) Prediction of relative glomerular filtration rate in adults: new improved equations based on Swedish Caucasians and standardized plasma-creatinine assays. Scand J Clin Lab Invest 67:678–695

    Article  PubMed  Google Scholar 

  15. Spinler SA, Nawarskas JJ, Boyce EG, Connors JE, Charland SL, Goldfarb S (1998) Predictive performance of ten equations for estimating creatinine clearance in cardiac patients. Iohexol Cooperative Study Group. Ann Pharmacother 32:1275–1283

    Article  CAS  PubMed  Google Scholar 

  16. Earley A, Miskulin D, Lamb EJ, Levey AS, Uhlig K (2012) Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review. Ann Intern Med 156:785–795

    Article  PubMed  Google Scholar 

  17. National Kidney Foundation (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Part 5. Evaluation of laboratory measurements for clinical assessment of kidney disease. Guideline 4. Estimation of GFR. Am J Kidney Dis 39:S 76–S 92

  18. Soveri I, Berg UB, Björk J, Elinder CG, Grubb A, Mejare I, Sterner G, Bäck SE, Group SGR (2014) Measuring GFR: a systematic review. Am J Kidney Dis 64:411–424

    Article  PubMed  Google Scholar 

  19. Andersen TB, Jodal L, Boegsted M, Erlandsen EJ, Morsing A, Frokiaer J, Brochner-Mortensen J (2012) GFR prediction from cystatin C and creatinine in children: effect of including body cell mass. Am J Kidney Dis 59:50–57

    Article  CAS  PubMed  Google Scholar 

  20. Bacchetta J, Cochat P, Rognant N, Ranchin B, Hadj-Aissa A, Dubourg L (2011) Which creatinine and cystatin C equations can be reliably used in children? Clin J Am Soc Nephrol 6:552–560

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Berg UB, Bäck R, Celsi G, Halling SE, Homberg I, Krmar RT, Åsling Monemi K, Öborn H, Herthelius M (2011) Comparison of plasma clearance of iohexol and urinary clearance of inulin for measurement of GFR in children. Am J Kidney Dis 57:55–61

  22. Blufpand HN, Tromp J, Abbink FC, Stoffel-Wagner B, Bouman AA, Schouten-van Meeteren AY, van Wijk JA, Kaspers GJ, Bokenkamp A (2011) Cystatin C more accurately detects mildly impaired renal function than creatinine in children receiving treatment for malignancy. Pediatr Blood Cancer 57:262–267

    Article  PubMed  Google Scholar 

  23. Pottel H, Mottaghy FM, Zaman Z, Martens F (2010) On the relationship between glomerular filtration rate and serum creatinine in children. Pediatr Nephrol 25:927–934

    Article  PubMed  Google Scholar 

  24. Swedish Council on Health Technology Assessment Methods to Estimate and Measure Kidney Function (glomerular filtration rate). A Systematic Review. 2013. Report no. 214. Accessed January 31, 2014).

  25. Nyman U, Björk J, Lindström V, Grubb A (2008) The Lund-Malmo creatinine-based glomerular filtration rate prediction equation for adults also performs well in children. Scand J Clin Lab Invest 68:568–576

    Article  CAS  PubMed  Google Scholar 

  26. Björk J, Grubb A, Larsson A, Hansson LO, Flodin M, Sterner G, Lindström V, Nyman U (2014) Accuracy of GFR estimating equations combining standardized cystatin C and creatinine assays: a cross-sectional study in Sweden. Clin Chem Lab Med. doi:10.1515/cclm-2014-0578

    PubMed  Google Scholar 

  27. Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, Kusek JW, Manzi J, Van Lente F, Zhang YL, Coresh J, Levey AS, Investigators C-E (2012) Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 367:20–29

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Nyman U, Grubb A, Sterner G, Björk J (2009) Different equations to combine creatinine and cystatin C to predict GFR. Arithmetic mean of existing equations performs as well as complex combinations. Scand J Clin Lab Invest 69:619–627

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Ulla B. Berg.

Additional information

Rune Bäck has passed away during the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Berg, U.B., Nyman, U., Bäck, R. et al. New standardized cystatin C and creatinine GFR equations in children validated with inulin clearance. Pediatr Nephrol 30, 1317–1326 (2015).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: