Advertisement

Pediatric Nephrology

, Volume 34, Issue 6, pp 1087–1098 | Cite as

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

  • Jonas Björk
  • Ulf NymanEmail author
  • Ulla Berg
  • Pierre Delanaye
  • Laurence Dubourg
  • Karolien Goffin
  • Anders Grubb
  • Magnus Hansson
  • Karin Littmann
  • Kajsa Åsling-Monemi
  • Arend Bökenkamp
  • Hans Pottel
Original Article

Abstract

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 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the World Medical Association Declaration of Helsinki of 1975, as revised in 2000.

Informed consent

For this type of retrospective study, all extracted data were fully anonymous without any personal information, why informed consent was not required according to the regional ethical board approval in, Lund, Sweden, which approved the study.

Supplementary material

467_2018_4185_MOESM1_ESM.pdf (482 kb)
ESM 1 (PDF 481 kb)

References

  1. 1.
    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 20:629–637CrossRefGoogle Scholar
  2. 2.
    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 6:552–560CrossRefGoogle Scholar
  3. 3.
    Schwartz GJ, Schneider MF, Maier PS, Moxey-Mims M, Dharnidharka VR, Warady BA, Furth SL, Munoz A (2012) Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney Int 82:445–453CrossRefGoogle Scholar
  4. 4.
    De Souza VC, Rabilloud M, Cochat P, Selistre L, Hadj-Aissa A, Kassai B, Ranchin B, Berg U, Herthelius M, Dubourg L (2012) Schwartz formula: is one k-coefficient adequate for all children? PLoS One 7:e53439CrossRefGoogle Scholar
  5. 5.
    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 59:50–57CrossRefGoogle Scholar
  6. 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 83:524–530CrossRefGoogle Scholar
  7. 7.
    Grubb A, Horio M, Hansson LO, Björk J, Nyman U, Flodin M, Larssson 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 60:974–986CrossRefGoogle Scholar
  8. 8.
    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 9:54–63CrossRefGoogle Scholar
  9. 9.
    Berg UB, Nyman U, Bäck R, Hansson M, Monemi KA, Herthelius M, Björk J (2015) New standardized cystatin C and creatinine GFR equations in children validated with inulin clearance. Pediatr Nephrol 30:1317–1326CrossRefGoogle Scholar
  10. 10.
    de Souza V, Cochat P, Rabilloud M, Selistre L, Wagner M, Hadj-Aissa A, Dolomanova O, Ranchin B, Iwaz J, Dubourg L (2015) Accuracy of different equations in estimating GFR in pediatric kidney transplant recipients. Clin J Am Soc Nephrol 10:463–470CrossRefGoogle Scholar
  11. 11.
    Deng F, Finer G, Haymond S, Brooks E, Langman CB (2015) Applicability of estimating glomerular filtration rate equations in pediatric patients: comparison with a measured glomerular filtration rate by iohexol clearance. Transl Res 165:437–445CrossRefGoogle Scholar
  12. 12.
    Pottel H, Hoste L, Dubourg L, Ebert N, Schaeffner E, Eriksen BO, Melsom T, Lamb EJ, Rule AD, Turner ST, Glassock RJ, De Souza V, Selistre L, Mariat C, Martens F, Delanaye P (2016) An estimated glomerular filtration rate equation for the full age spectrum. Nephrol Dial Transplant 31:798–806CrossRefGoogle Scholar
  13. 13.
    Pottel H, Delanaye P, Schaeffner E, Dubourg L, Eriksen BO, Melsom T, Lamb EJ, Rule AD, Turner ST, Glassock RJ, De Souza V, Selistre L, Goffin K, Pauwels S, Mariat C, Flamant M, Ebert N (2017) Estimating glomerular filtration rate for the full age spectrum from serum creatinine and cystatin C. Nephrol Dial Transplant 32:497–507Google Scholar
  14. 14.
    Blufpand HN, Tromp J, Abbink FC, Stoffel-Wagner B, Bouman AA, Schouten-van Meeteren AY, van Wijk JA, Kaspers GJ, Bökenkamp A (2011) Cystatin C more accurately detects mildly impaired renal function than creatinine in children receiving treatment for malignancy. Pediatr Blood Cancer 57:262–267CrossRefGoogle Scholar
  15. 15.
    Blufpand HN, Westland R, van Wijk JA, Roelandse-Koop EA, Kaspers GJ, Bökenkamp A (2013) Height-independent estimation of glomerular filtration rate in children: an alternative to the Schwartz equation. J Pediatr 163:1722–1727CrossRefGoogle Scholar
  16. 16.
    Westland R, Abraham Y, Bokenkamp A, Stoffel-Wagner B, Schreuder MF, van Wijk JA (2013) Precision of estimating equations for GFR in children with a solitary functioning kidney: the KIMONO study. Clin J Am Soc Nephrol 8:764–772CrossRefGoogle Scholar
  17. 17.
    den Bakker E, Gemke R, van Wijk JAE, Hubeek I, Stoffel-Wagner B, Grubb A, Bökenkamp A (2017) Accurate eGFR reporting for children without anthropometric data. Clin Chim Acta 474:38–43CrossRefGoogle Scholar
  18. 18.
    Mueller L, Pruemper C (2016) Performance in measurement of serum cystatin C by laboratories participating in the College of American Pathologists 2014 CYS Survey. Arch Pathol Lab Med 140:207–208CrossRefGoogle Scholar
  19. 19.
    Hoste L, Dubourg L, Selistre L, De Souza VC, Ranchin B, Hadj-Aissa A, Cochat P, Martens F, Pottel H (2014) A new equation to estimate the glomerular filtration rate in children, adolescents and young adults. Nephrol Dial Transplant 29:1082–1091CrossRefGoogle Scholar
  20. 20.
    Björk J, Grubb A, Sterner G, Nyman U (2011) Revised equations for estimating glomerular filtration rate based on the Lund-Malmö Study cohort. Scand J Clin Lab Invest 71:232–239CrossRefGoogle Scholar
  21. 21.
    Leion F, Hegbrant J, den Bakker E, Jonsson M, Abrahamson M, Nyman U, Björk J, Lindström V, Larsson A, Bökenkamp A, Grubb A (2017) Estimating glomerular filtration rate (GFR) in children. The average between a cystatin C- and a creatinine-based equation improves estimation of GFR in both children and adults and enables diagnosing Shrunken Pore Syndrome. Scand J Clin Lab Invest 77:338–344CrossRefGoogle Scholar
  22. 22.
    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 (2012) Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 367:20–29CrossRefGoogle Scholar
  23. 23.
    K/DOQI clinical practice guidelines for chronic kidney disease (2002) 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:S76–S92CrossRefGoogle Scholar
  24. 24.
    Pottel H, Hoste L, Delanaye P (2015) Abnormal glomerular filtration rate in children, adolescents and young adults starts below 75 mL/min/1.73 m(2). Pediatr Nephrol 30:821–828CrossRefGoogle Scholar
  25. 25.
    Barlow SE (2007) Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics 120(Suppl 4):S164–S192CrossRefGoogle Scholar
  26. 26.
    Fredriks AM, van Buuren S, Wit JM, Verloove-Vanhorick SP (2000) Body index measurements in 1996–7 compared with 1980. Arch Dis Child 82:107–112CrossRefGoogle Scholar
  27. 27.
    Eckfeldt JH, Karger AB, Miller WG, Rynders GP, Inker LA (2015) Performance in measurement of serum cystatin C by laboratories participating in the College of American pathologists 2014 CYS survey. Arch Pathol Lab Med 139:888–893CrossRefGoogle Scholar
  28. 28.
    Bargnoux AS, Pieroni L, Cristol JP, Kuster N, Delanaye P, Carlier MC, Fellahi S, Boutten A, Lombard C, Gonzalez-Antuna A, Delatour V, Cavalier E (2017) Multicenter evaluation of cystatin C measurement after assay standardization. Clin Chem 63:833–841CrossRefGoogle Scholar
  29. 29.
    Nordin G (2017) Cystatin C-incremental improvement in measurement and understanding of results. Clin Chem 63:802–803CrossRefGoogle Scholar
  30. 30.
    Groesbeck D, Kottgen A, Parekh R, Selvin E, Schwartz GJ, Coresh J, Furth S (2008) Age, gender, and race effects on cystatin C levels in US adolescents. Clin J Am Soc Nephrol 3:1777–1785CrossRefGoogle Scholar
  31. 31.
    Yata N, Uemura O, Honda M, Matsuyama T, Ishikura K, Hataya H, Nagai T, Ikezumi Y, Fujita N, Ito S, Iijima K, Saito M, Keneko T, Kitagawa T (2013) Reference ranges for serum cystatin C measurements in Japanese children by using 4 automated assays. Clin Exp Nephrol 17:872–876CrossRefGoogle Scholar
  32. 32.
    Schwartz GJ, Brion LP, Spitzer A (1987) The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 34:571–590CrossRefGoogle Scholar
  33. 33.
    Björk J, Jones I, Nyman U, Sjöström P (2012) Validation of the Lund-Malmö, Chronic Kidney Disease Epidemiology (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations to estimate glomerular filtration rate in a large Swedish clinical population. Scand J Urol Nephrol 46:212–222CrossRefGoogle Scholar
  34. 34.
    Evans M, van Stralen KJ, Schon S, Prutz KG, Stendahl M, Rippe B, Jager KJ (2013) Glomerular filtration rate-estimating equations for patients with advanced chronic kidney disease. Nephrol Dial Transplant 28:2518–2526CrossRefGoogle Scholar
  35. 35.
    Björk J, Grubb A, Gudnason V, Indridason OS, Levey AS, Palsson R, Nyman U (2017) Comparison of glomerular filtration rate estimating equations derived from creatinine and cystatin C: validation in the Age, Gene/Environment Susceptibility-Reykjavik elderly cohort. Nephrol Dial Transplant 33:1389–1388Google Scholar
  36. 36.
    Ebert N, Loesment A, Martus P, Jakob O, Gaedeke J, Kuhlmann M, Bartel J, Schuchardt M, Tolle M, Huang T, van der Giet M, Schaeffner E (2015) Iohexol plasma clearance measurement in older adults with chronic kidney disease-sampling time matters. Nephrol Dial Transplant 30:1307–1314CrossRefGoogle Scholar
  37. 37.
    Nyman U, Grubb A, Larsson A, Hansson LO, Flodin M, Nordin G, Lindström V, Björk J (2014) The revised Lund-Malmo GFR estimating equation outperforms MDRD and CKD-EPI across GFR, age and BMI intervals in a large Swedish population. Clin Chem Lab Med 52:815–824CrossRefGoogle Scholar
  38. 38.
    Björk J, Bäck SE, Ebert N, Evans M, Grubb A, Hansson M, Jones I, Lamb EJ, Martus P, Schäffner E, Sjöström P, Nyman U (2018) GFR estimation based on standardized creatinine and cystatin C: a European multicenter analysis in older adults. Clin Chem Lab Med 56:422–435CrossRefGoogle Scholar
  39. 39.
    Selistre L, De Souza V, Cochat P, Antonello IC, Hadj-Aissa A, Ranchin B, Dolomanova O, Varennes A, Beyerle F, Bacchetta J, Dubourg L (2012) GFR estimation in adolescents and young adults. J Am Soc Nephrol 23:989–996CrossRefGoogle Scholar
  40. 40.
    Ng DK, Schwartz GJ, Schneider MF, Furth SL, Warady BA (2018) Combination of pediatric and adult formulas yield valid glomerular filtration rate estimates in young adults with a history of pediatric chronic kidney disease. Kidney Int 94:170–177CrossRefGoogle Scholar
  41. 41.
    den Bakker E, Gemke R, Bökenkamp A (2018) Endogenous markers for kidney function in children: a review. Critical reviews in clinical laboratory sciences 55:163–183CrossRefGoogle Scholar
  42. 42.
    Nyman U, Björk J, Lindström V, Grubb A (2008) The Lund-Malmö creatinine-based glomerular filtration rate prediction equation for adults also performs well in children. Scand J Clin Lab Invest 68:568–576CrossRefGoogle Scholar
  43. 43.
    Björk J, Grubb A, Larsson A, Hansson LO, Flodin M, Sterner G, Lindström V, Nyman U (2015) Accuracy of GFR estimating equations combining standardized cystatin C and creatinine assays: a cross-sectional study in Sweden. Clin Chem Lab Med 53:403–414CrossRefGoogle Scholar
  44. 44.
    den Bakker E, Gemke R, van Wijk JAE, Hubeek I, Stoffel-Wagner B, Bökenkamp A (2018) Combining GFR estimates from cystatin C and creatinine—what is the optimal mix? Pediatr Nephrol 33:1553–1563CrossRefGoogle Scholar
  45. 45.
    Grubb A (2010) Non-invasive estimation of glomerular filtration rate (GFR). The Lund model: simultaneous use of cystatin C- and creatinine-based GFR-prediction equations, clinical data and an internal quality check. Scand J Clin Lab Invest 70:65–70CrossRefGoogle Scholar
  46. 46.
    van Roij KG, van der Horst HJ, Hubeek I, van Wijk JA, Bökenkamp A (2017) Discrepant results of serum creatinine and cystatin C in a urological patient. Clin Chem 63:812–814CrossRefGoogle Scholar

Copyright information

© IPNA 2019

Authors and Affiliations

  • Jonas Björk
    • 1
    • 2
  • Ulf Nyman
    • 3
    Email author
  • Ulla Berg
    • 4
  • Pierre Delanaye
    • 5
  • Laurence Dubourg
    • 6
  • Karolien Goffin
    • 7
  • Anders Grubb
    • 8
  • Magnus Hansson
    • 9
  • Karin Littmann
    • 9
  • Kajsa Åsling-Monemi
    • 4
  • Arend Bökenkamp
    • 10
  • Hans Pottel
    • 11
  1. 1.Division of Occupational and Environmental MedicineLund UniversityLundSweden
  2. 2.Clinical Studies Sweden, Forum SouthSkåne University HospitalLundSweden
  3. 3.Department of Translational Medicine, Division of Medical RadiologyLund UniversityMalmöSweden
  4. 4.Department of Clinical Science, Intervention and Technology, Division of Paediatrics, Karolinska InstitutetKarolinska University Hospital HuddingeStockholmSweden
  5. 5.Nephrology-Dialysis-TransplantationUniversity of LiègeLiègeBelgium
  6. 6.Néphrologie, Dialyse, Hypertension et Exploration Fonctionnelle Rénale, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, and Laboratory of Tissue Biology and Therapeutic Engineering, UMR 5305 CNRSUniversité Claude Bernard Lyon 1LyonFrance
  7. 7.Department of Nuclear Medicine & Molecular ImagingUniversity Hospital LeuvenLeuvenBelgium
  8. 8.Department of Clinical Chemistry, Skåne University Hospital, LundLund UniversityLundSweden
  9. 9.Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska InstitutetKarolinska University Hospital HuddingeStockholmSweden
  10. 10.Emma Children’s Hospital, Amsterdam UMCVrije Universiteit AmsterdamAmsterdamThe Netherlands
  11. 11.Department of Public Health and Primary CareKU Leuven Campus Kulak KortrijkKortrijkBelgium

Personalised recommendations