Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children

Pediatr Nephrol. 2019 Jun;34(6):1087-1098. doi: 10.1007/s00467-018-4185-y. Epub 2019 Feb 4.


Background: Most validations of paediatric glomerular filtration rate (GFR) estimating equations using standardized creatinine (CR) and cystatin C (CYS) assays have comprised relatively small cohorts, which makes accuracy across subgroups of GFR, age, body mass index (BMI) and gender uncertain. To overcome this, a large cohort of children referred for GFR determination has been established from several European medical centres.

Methods: Three thousand four hundred eight measurements of GFR (mGFR) using plasma clearance of exogenous substances were performed in 2218 children aged 2-17 years. Validated equations included Schwartz-2009CR/2012CR/CYS/CR+CYS, FASCR/CYS/CR+CYS, LMRCR, Schwartz-LyonCR, BergCYS, CAPACYS, CKD-EPICYS, AndersenCR+CYS and arithmetic means of the best single-marker equations in explorative analysis. Five metrics were used to compare the performance of the GFR equations: bias, precision and three accuracy measures including the percentage of GFR estimates (eGFR) within ± 10% (P10) and ± 30% (P30) of mGFR.

Results: Three of the cystatin C equations, BergCYS, CAPACYS and CKD-EPICYS, exhibited low bias and generally satisfactory accuracy across all levels of mGFR; CKD-EPICYS had more stable performance across gender than the two other equations. Among creatinine equations, Schwartz-LyonCR had the best performance but was inaccurate at mGFR < 30 mL/min/1.73 m2 and in underweight patients. Arithmetic means of the best creatinine and cystatin C equations above improved bias compared to the existing composite creatinine+cystatin C equations.

Conclusions: The present study strongly suggests that cystatin C should be the primary biomarker of choice when estimating GFR in children with decreased GFR. Arithmetic means of well-performing single-marker equations improve accuracy further at most mGFR levels and have practical advantages compared to composite equations.

Keywords: Children; Chronic kidney disease; Glomerular filtration rate; Kidney function tests; Renal failure.

Publication types

  • Multicenter Study
  • Validation Study

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cohort Studies
  • Creatinine / blood*
  • Cystatin C / blood*
  • Europe
  • Female
  • Glomerular Filtration Rate*
  • Humans
  • Kidney Function Tests / standards*
  • Male
  • Mass Spectrometry / methods
  • Mass Spectrometry / standards


  • CST3 protein, human
  • Cystatin C
  • Creatinine