Skip to main content
SpringerLink
Log in

Recalibration of cystatin C using standardized material in Siemens nephelometers

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

Abstract

Background

Cystatin C is a key GFR biomarker. Recently, Siemens recalibrated the assay based on certified reference material ERM-DA471/IFCC. The NIH-funded longitudinal chronic kidney disease in children (CKiD) study has > 3000 cystatin C measurements based on a pre-IFCC calibrator provided by Siemens. Since cystatin C values for CKiD are now standardized to IFCC certified reference material, it is important to relate the IFCC-calibrated results to the previous values so that there are no discontinuous results.

Methods

We diluted cystatin C ERM-DA471/IFCC (5.48 mg/L) into buffer and compared results with predicted ones. We then updated the cystatin C application on our BN II nephelometer to provide results based on pre-IFCC and IFCC calibrations of CKiD specimens simultaneously. We assayed 51 previously analyzed sera and 62 fresh additional specimens.

Results

The predicted concentrations from the IFCC standard were consistently 17% higher than the measured values using the pre-IFCC calibration (y = 1.1686x). Similarly, the re-run and fresh sample concentrations were 17% higher via the IFCC calibration than by the pre-IFCC calibration (y = 1.168x). There was very high reliability in the measurements using the previous calibration for re-run specimens (0.99) and for 33 pristine specimens using IFCC calibration (0.99).

Conclusions

We confirm the recalibration proposed by Siemens. To convert pre-IFCC results to IFCC-calibrated concentrations, the value is multiplied by 1.17. Conversely, one divides IFCC-calibrated results by 1.17 to estimate GFR via previously published pre-IFCC CKiD eGFR equations. For older adolescents, cystatin C has already been standardized and can be directly applied to the CKD-EPI equations.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. 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 82:445–453. https://doi.org/10.1038/ki.2012.169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Dharnidharka VR, Kwon C, Stevens G (2002) Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis 40:221–226

    Article  CAS  Google Scholar 

  3. Stevens LA, Coresh J, Schmid CH, Feldman HI, Froissart M, Kusek J, Rossert J, Van Lente F, Bruce RD 3rd, Zhang YL, Greene T, Levey AS (2008) Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis 51:395–406. https://doi.org/10.1053/j.ajkd.2007.11.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Inker LA, Eckfeldt J, Levey AS, Leiendecker-Foster C, Rynders G, Manzi J, Waheed S, Coresh J (2011) Expressing the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) cystatin C equations for estimating GFR with standardized serum cystatin C values. Am J Kidney Dis 58:682–684. https://doi.org/10.1053/j.ajkd.2011.05.019

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. Rodenbach KE, Fuhrman DY, Maier PS, Schwartz GJ (2017) Renal response to a protein load in healthy young adults as determined by iohexol infusion clearance, cimetidine-inhibited creatinine clearance, and cystatin C estimated glomerular filtration rate. J Ren Nutr 27:275–281. https://doi.org/10.1053/j.jrn.2017.01.021

    Article  CAS  PubMed  Google Scholar 

  7. 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. https://doi.org/10.5858/arpa.2015-0353-LE

    Article  PubMed  Google Scholar 

  8. Rule AD, Bergstralh EJ, Slezak JM, Bergert J, Larson TS (2006) Glomerular filtration rate estimated by cystatin C among different clinical presentations. Kidney Int 69:399–405

    Article  CAS  Google Scholar 

  9. Carroll RJ, Ruppert D, Stefanski LA, Crainiceanu CM (2006) Measurement error in nonlinear models: a modern perspective. Mongraphs on Statistics and Applied Probability 105, vol 105, Second edn. Chapman & Hall/CRC, Boca Raton, FL

  10. Newman DJ (2002) Cystatin C. Ann Clin Biochem 39:89–104

    Article  CAS  Google Scholar 

  11. 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 139:888–893. https://doi.org/10.5858/arpa.2014-0427-CP

    Article  CAS  PubMed  Google Scholar 

  12. Ebert N, Delanaye P, Shlipak M, Jakob O, Martus P, Bartel J, Gaedeke J, van der Giet M, Schuchardt M, Cavalier E, Schaeffner E (2016) Cystatin C standardization decreases assay variation and improves assessment of glomerular filtration rate. Clin Chim Acta 456:115–121. https://doi.org/10.1016/j.cca.2016.03.002

    Article  CAS  PubMed  Google Scholar 

  13. Hoek FJ, Kemperman FA, Krediet RT (2003) A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular filtration rate. Nephrol Dial Transplant 18:2024–2031

    Article  CAS  Google Scholar 

  14. 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  Google Scholar 

  15. Le BT, Thervet E, Froissart M, Benlakehal M, Bousquet B, Legendre C, Erlich D (2000) Plasma cystatin C is superior to 24-h creatinine clearance and plasma creatinine for estimation of glomerular filtration rate 3 months after kidney transplantation. Clin Chem 46:1206–1207

    Google Scholar 

  16. 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 48:221–230

    Article  CAS  Google Scholar 

  17. Nyman U, Grubb A, Sterner G, Bjork 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. https://doi.org/10.1080/00365510902946992

    Article  CAS  PubMed  Google Scholar 

  18. Larsson A, Malm J, Grubb A, Hansson LO (2004) Calculation of glomerular filtration rate expressed in mL/min from plasma cystatin C values in mg/L. Scand J Clin Lab Invest 64:25–30

    Article  CAS  Google Scholar 

  19. Hojs R, Bevc S, Ekart R, Gorenjak M, Puklavec L (2010) Serum cystatin C-based formulas for prediction of glomerular filtration rate in patients with chronic kidney disease. Nephron Clin Pract 114:c118–c126. https://doi.org/10.1159/000254384

    Article  CAS  PubMed  Google Scholar 

  20. Zhao Z, Sacks DB (2016) Detrimental effects of not using international reference materials to calibrate cystatin C assays. Clin Chem 62:410–411. https://doi.org/10.1373/clinchem.2015.244988

    Article  CAS  PubMed  Google Scholar 

  21. Larsson A, Hansson LO, Flodin M, Katz R, Shlipak MG (2011) Calibration of the Siemens cystatin C immunoassay has changed over time. Clin Chem 57:777–778. https://doi.org/10.1373/clinchem.2010.159848

    Article  CAS  PubMed  Google Scholar 

  22. 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  Google Scholar 

  23. Schwartz GJ, Kwong T, Erway B, Warady B, Sokoll L, Hellerstein S, Dharnidharka V, Furth S, Munoz A (2009) Validation of creatinine assays utilizing HPLC and IDMS traceable standards in sera of children. Pediatr Nephrol 24:113–119

    Article  Google Scholar 

  24. Vervoort G, Klein Gunnewiek JM, Willems HL, Wetzels JF (2006) Effect of creatinine assay standardization on the performance of Cockcroft-Gault and MDRD formula in predicting GFR. Nephrol Dial Transplant 21:2998–2999. https://doi.org/10.1093/ndt/gfl276

    Article  CAS  PubMed  Google Scholar 

  25. Van Biesen W, Vanholder R, Veys N, Verbeke F, Delanghe J, De Bacquer D, Lameire N (2006) The importance of standardization of creatinine in the implementation of guidelines and recommendations for CKD: implications for CKD management programmes. Nephrol Dial Transplant 21:77–83. https://doi.org/10.1093/ndt/gfi185

    Article  PubMed  Google Scholar 

  26. 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, CKD-EPI Investigators (2012) Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 367:20–29. https://doi.org/10.1056/NEJMoa1114248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

Data in this manuscript were collected by the chronic kidney disease in children (CKiD) prospective study with clinical coordinating centers at Children’s Mercy Hospital (BAW and the University of Missouri—Kansas City (BAW) and the Children’s Hospital of Philadelphia (SLF), Data Coordinating Center at the Johns Hopkins Bloomberg School of Public Health (AM, DN), and the Central Biochemistry Laboratory at the University of Rochester Medical Center (GJS).

Funding

The CKiD study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the National Institute of Neurological Disorders and Stroke, the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01-DK66143, U01-DK66174, U24-DK66116, U24-DK82194). The CKiD website is located at http://www.statepi.jhsph.edu/ckid.

Author information

Authors and Affiliations

  1. University of Rochester Medical Center, Box 777, 601 Elmwood Avenue, Rochester, NY, USA

    George J. Schwartz, Paula S. Maier & Donna DiManno

  2. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Christopher Cox & Alvaro Munoz

  3. University of Minnesota, Minneapolis, MN, USA

    Jesse C. Seegmiller

  4. Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Sue L. Furth

  5. Children’s Mercy Hospital, Kansas City, MO, USA

    Bradley A. Warady

Authors
  1. George J. Schwartz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher Cox
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jesse C. Seegmiller
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paula S. Maier
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Donna DiManno
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sue L. Furth
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bradley A. Warady
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alvaro Munoz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George J. Schwartz.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schwartz, G.J., Cox, C., Seegmiller, J.C. et al. Recalibration of cystatin C using standardized material in Siemens nephelometers. Pediatr Nephrol 35, 279–285 (2020). https://doi.org/10.1007/s00467-019-04389-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-019-04389-2

Keywords

Search

Navigation