Advertisement

Pediatric Nephrology

, Volume 33, Issue 9, pp 1553–1563 | Cite as

Combining GFR estimates from cystatin C and creatinine—what is the optimal mix?

  • Emil den Bakker
  • Reinoud Gemke
  • Joanna A. E. van Wijk
  • Isabelle Hubeek
  • Birgit Stoffel-Wagner
  • Arend Bökenkamp
Original Article

Abstract

Background

Combining estimated glomerular filtration rate (eGFR) equations based on creatinine and cystatin C has been shown to improve the accuracy of GFR estimation. This study aims to optimize this strategy for height-independent GFR estimation in children.

Methods

Retrospective study of 408 inulin clearance tests with simultaneous International Federation of Clinical Chemistry-calibrated measurements of creatinine, cystatin C, and urea in children (mean age 12.5 years, GFR 91.2 ml/min/1.73m2) comparing the arithmetic (meanarith) and geometric means (meangeom) of a height-independent creatinine-based (full age spectrum, based on age (FASage)) and a cystatin C-based equation (FAScys), with the complex height-dependent CKiD3 equation incorporating gender, height, cystatin C, creatinine, and urea.

Results

Meangeom had a P30 accuracy of 89.2% compared to meanarith 87.7% (p = 0.030) as well as lower bias and %precision error and performed almost as well as CKiD3 (P30 accuracy 90.9%). Modifying the weight of FASage and FAScys when calculating the means showed that an equal contribution was most accurate in most patients. In spina bifida patients, FAScys alone outperformed any combination. Malignancy or nephritis patients had slightly higher accuracy with weighted means favoring cystatin C or creatinine, respectively. Disagreement between FAScys and FASage was inversely correlated with the accuracy of meangeom. When disagreement exceeded 40%, application of weighted means based on diagnosis improved the performance of eGFR.

Conclusions

In the absence of height data, the optimal strategy for estimating GFR in children is by using the geometric mean of FASage and FAScys. When there is large disagreement between the two, weighted means based on diagnosis improve accuracy.

Keywords

Height-independent eGFR Creatinine Cystatin C Children 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary material

467_2018_3973_MOESM1_ESM.docx (16 kb)
ESM 1 (DOCX 15 kb)

References

  1. 1.
    Greer RC, Powe NR, Jaar BG, Troll MU, Boulware LE (2011) Effect of primary care physicians’ use of estimated glomerular filtration rate on the timing of their subspecialty referral decisions. BMC Nephrol 12:1CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Sjöström P, Tidman M, Jones I (2005) Determination of the production rate and non-renal clearance of cystatin C and estimation of the glomerular filtration rate from the serum concentration of cystatin C in humans. Scand J Clin Lab Invest 65:111–124CrossRefPubMedGoogle Scholar
  3. 3.
    Bökenkamp A, Domanetzki M, Zinck R, Schumann G, Brodehl J (1998) Reference values for cystatin C serum concentrations in children. Pediatr Nephrol 12:125–129CrossRefPubMedGoogle Scholar
  4. 4.
    Schwartz GJ, Schneider MF, Maier PS, Moxey-Mims M, Dharnidharka VR, Warady BA, Furth SL, Muñoz A (2012) Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney Int 82:445–453CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Nagai T, Uemura O, Ishikura K, Ito S, Hataya H, Gotoh Y, Fujita N, Akioka Y, Kaneko T, Honda M (2013) Creatinine-based equations to estimate glomerular filtration rate in Japanese children aged between 2 and 11 years old with chronic kidney disease. Clin Exp Nephrol 17:877–881CrossRefPubMedGoogle Scholar
  6. 6.
    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 31:798–806CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    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 32:497–507PubMedPubMedCentralGoogle Scholar
  8. 8.
    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 60:974–986CrossRefPubMedGoogle Scholar
  9. 9.
    Uemura O, Nagai T, Ishikura K, Ito S, Hataya H, Gotoh Y, Fujita N, Akioka Y, Kaneko T, Honda M (2014) Cystatin C-based equation for estimating glomerular filtration rate in Japanese children and adolescents. Clin Exp Nephrol 18:718–725CrossRefPubMedGoogle Scholar
  10. 10.
    Filler G, Lepage N (2003) Should the Schwartz formula for estimation of GFR be replaced by cystatin C formula? Pediatr Nephrol 18:981–985CrossRefPubMedGoogle Scholar
  11. 11.
    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
  12. 12.
    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 77:338–344CrossRefPubMedGoogle Scholar
  13. 13.
    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 69:619–627CrossRefPubMedGoogle Scholar
  14. 14.
    Gabutti L, Ferrari N, Mombelli G, Marone C (2004) Does cystatin C improve the precision of Cockcroft and Gault's creatinine clearance estimation? J Nephrol 17:673–678PubMedGoogle Scholar
  15. 15.
    Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, (Collaboration) C-ECKDE (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Westland R, Abraham Y, Bökenkamp 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 8:764–772CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Jung K, Klotzek S, Schulze BD (1990) Refinements of assays for low concentrations of inulin in serum. Nephron 54:360–361CrossRefPubMedGoogle Scholar
  18. 18.
    Degenaar CP, Frenken LAM, von Hooff JP (1987) Enzymatic method for the determination of inulin. Clin Chem 33:1070–1071PubMedGoogle Scholar
  19. 19.
    van Rossum LK, Mathot RA, Cransberg K, Vulto AG (2003) Optimal sampling strategies to assess inulin clearance in children by the inulin single-injection method. Clin Chem 49:1170–1179CrossRefPubMedGoogle Scholar
  20. 20.
    Suzuki M, Yoshida M (1984) A new enzymatic serum creatinine measurement based on an endogenous creatine-eliminating system. Clin Chim Acta 143:147–155CrossRefPubMedGoogle Scholar
  21. 21.
    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 140:207CrossRefPubMedGoogle Scholar
  22. 22.
    Hoste L, Dubourg L, Selistre L, De Souza VC, Ranchin B, Hadj-Aïssa 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 29:1082–1091CrossRefPubMedGoogle Scholar
  23. 23.
    Grubb A, Blirup-Jensen S, Lindström V, Schmidt C, Althaus H, Zegers I, IFCC Working Group on Standardization of Cystatin C (2010) First certified reference material for cystatin C in human serum ERM-DA471/IFCC. Clin Chem Lab Med 48:1619–1621CrossRefPubMedGoogle Scholar
  24. 24.
    Grubb A, Nyman U, Björk J (2012) Improved estimation of glomerular filtration rate (GFR) by comparison of eGFRcystatin C and eGFRcreatinine. Scand J Clin Lab Invest 72:73–77CrossRefPubMedGoogle Scholar
  25. 25.
    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 63:812–814CrossRefPubMedGoogle Scholar
  26. 26.
    Pottel H, Dubourg L, Goffin K, Delanaye P (2018) Alternatives for the bedside Schwartz equation to estimate glomerular filtration rate in children. Adv Chronic Kidney Dis 25:57–66CrossRefPubMedGoogle Scholar
  27. 27.
    Rule AD, Bergstralh EJ, Slezak JM, Bergert J, Larson TS (2006) Glomerular filtration rate estimated by cystatin C among different clinical presentations. Kidney Int 69:399–405CrossRefPubMedGoogle Scholar
  28. 28.
    Zappitelli M, Parvex P, Joseph L, Paradis G, Grey V, Lau S, Bell L (2006) Derivation and validation of cystatin C-based prediction equations for GFR in children. Am J Kidney Dis 48:221–230CrossRefPubMedGoogle Scholar
  29. 29.
    Filler G, Lee M (2017) Educational review: measurement of GFR in special populations. Pediatr Nephrol.  https://doi.org/10.1007/s00467-017-3852-8
  30. 30.
    Baxmann AC, Ahmed MS, Marques NC, Menon VB, Pereira AB, Kirsztajn GM, Heilberg IP (2008) Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C. Clin J Am Soc Nephrol 3:348–354CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Pham-Huy A, Leonard M, Lepage N, Halton J, Filler G (2003) Measuring glomerular filtration rate with cystatin C and beta-trace protein in children with spina bifida. J Urol 169:2312–2315CrossRefPubMedGoogle Scholar
  32. 32.
    Rayar M, Webber CE, Nayiager T, Sala A, Barr RD (2013) Sarcopenia in children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol 35:98–102CrossRefPubMedGoogle Scholar
  33. 33.
    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 57:262–267CrossRefPubMedGoogle Scholar
  34. 34.
    Whiting P, Birnie K, Sterne JAC, Jameson C, Skinner R, Phillips B, Cystatin C in Childhood Cancer Collaboration Group (2017) Accuracy of cystatin C for the detection of abnormal renal function in children undergoing chemotherapy for malignancy: a systematic review using individual patient data. Support Care Cancer 26:1635–1644PubMedGoogle Scholar
  35. 35.
    Abbink FC, Laarman CA, Braam KI, van Wijk JA, Kors WA, Bouman AA, Spreeuwenberg MD, Stoffel-Wagner B, Bökenkamp A (2008) Beta-trace protein is not superior to cystatin C for the estimation of GFR in patients receiving corticosteroids. Clin Biochem 41:299–305CrossRefPubMedGoogle Scholar
  36. 36.
    Bökenkamp A, Laarman CA, Braam KI, van Wijk JA, Kors WA, Kool M, de Valk J, Bouman AA, Spreeuwenberg MD, Stoffel-Wagner B (2007) Effect of corticosteroid therapy on low-molecular weight protein markers of kidney function. Clin Chem 53:2219–2221CrossRefPubMedGoogle Scholar
  37. 37.
    Bjarnadóttir M, Grubb A, Olafsson I (1995) Promoter-mediated, dexamethasone-induced increase in cystatin C production by HeLa cells. Scand J Clin Lab Invest 55:617–623CrossRefPubMedGoogle Scholar
  38. 38.
    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 53:403–414CrossRefPubMedGoogle Scholar
  39. 39.
    den Bakker E, Gemke RJBJ, Bökenkamp A (2018) Endogenous markers for kidney function in children: a review. Crit Rev Clin Lab Sci 55:163–183CrossRefGoogle Scholar
  40. 40.
    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 70:65–70CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Pöge U, Gerhardt T, Bökenkamp A, Stoffel-Wagner B, Klehr HU, Sauerbruch T, Woitas RP (2004) Time course of low molecular weight proteins in the early kidney transplantation period—influence of corticosteroids. Nephrol Dial Transplant 19:2858–2863CrossRefPubMedGoogle Scholar
  42. 42.
    Brinkert F, Kemper MJ, Briem-Richter A, van Husen M, Treszl A, Ganschow R (2011) High prevalence of renal dysfunction in children after liver transplantation: non-invasive diagnosis using a cystatin C-based equation. Nephrol Dial Transplant 26:1407–1412CrossRefPubMedGoogle Scholar
  43. 43.
    Pöge U, Gerhardt T, Stoffel-Wagner B, Klehr HU, Sauerbruch T, Woitas RP (2006) Calculation of glomerular filtration rate based on cystatin C in cirrhotic patients. Nephrol Dial Transplant 21:660–664CrossRefPubMedGoogle Scholar
  44. 44.
    Mangge H, Liebmann P, Tanil H, Herrmann J, Wagner C, Gallistl S, Schauenstein K, Erwa W (2000) Cystatin C, an early indicator for incipient renal disease in rheumatoid arthritis. Clin Chim Acta 300:195–202CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2018

Authors and Affiliations

  1. 1.Department of PediatricsVU University Medical CenterAmsterdamThe Netherlands
  2. 2.Department of Pediatric NephrologyVU University Medical CenterAmsterdamThe Netherlands
  3. 3.Department of Clinical ChemistryVU University Medical CenterAmsterdamThe Netherlands
  4. 4.Department of Clinical Chemistry and Clinical PharmacologyUniversity ClinicsBonnGermany

Personalised recommendations