Skip to main content
SpringerLink
Log in

Validation of creatinine assays utilizing HPLC and IDMS traceable standards in sera of children

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

Abstract

The purpose of this study was to validate serum creatinine (SCr) concentrations assayed in the Central Biochemistry Laboratory of the National Institutes of Health (NIH)-funded Chronic Kidney Disease in Children (CKiD) study utilizing an enzymatic assay (Siemens Advia 2400) against a method traceable to reference isotope dilution mass spectroscopy (IDMS) developed by the National Institute of Standards and Technology (NIST). High-performance liquid chromatography (HPLC) measured SCr after external validation utilizing IDMS-based standard reference materials. Sera from the first 201 subjects enrolled in CKiD were analyzed and compared for creatinine concentration by enzymatic and HPLC methods. Fifty “normal” pediatric sera were subsequently analyzed. Finally, a “pediatric” reference standard was prepared and examined for accuracy and precision. Enzymatic SCr concentrations (median 1.4 mg/dl) of CKiD subjects were well correlated with HPLC (r = 0.984) but were slightly higher (+7%; p < 0.001). Agreement was poorer at lower SCr (median 0.4 mg/dl) when using samples from normal children and the “pediatric” reference standard. However, the Roche enzymatic assay was comparable with HPLC in accuracy and precision. Referring physicians should be aware of the accuracy and reproducibility of their laboratory’s SCr assay. Our enzymatic assay agreed well with HPLC in CKiD subjects with elevated SCr. We suggest that NIST develop a pediatric SCr standard reference material for use by assay manufacturers to improve accuracy and precision of assays at the low SCr levels observed in most pediatric patients.

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
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. 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 34:571–590

    Article  CAS  Google Scholar 

  2. Hogg RJ, Furth S, Lemley KV, Portman R, Schwartz GJ, Coresh J, Balk E, Lau J, Levin A, Kausz AT, Eknoyan G, Levey AS (2003) National Kidney Foundation’s kidney disease outcomes quality initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification. Pediatrics 111:1416–1421

    Article  Google Scholar 

  3. Myers GL, Miller WG, Coresh J, Fleming J, Greenberg N, Greene T, Hostetter T, Levey AS, Panteghini M, Welch M, Eckfeldt JH (2006) Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program. Clin Chem 52:5–18

    Article  CAS  Google Scholar 

  4. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers NL, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 130:461–470

    Article  CAS  Google Scholar 

  5. Schwartz GJ, Haycock GB, Chir B, Spitzer A (1976) Plasma creatinine and urea concentration in children: normal values for age and sex. J Pediatr 88:828–830

    Article  CAS  Google Scholar 

  6. Keppler A, Gretz N, Schmidt R, Kloetzer HM, Groene HJ, Lelongt B, Meyer M, Sadick M, Pill J (2007) Plasma creatinine determination in mice and rats: an enzymatic method compares favorably with a high-performance liquid chromatography assay. Kidney Int 71:74–78

    Article  CAS  Google Scholar 

  7. Ambrose RT, Ketchum DF, Smith JW (1983) Creatinine determined by “high-performance” liquid chromatography. Clin Chem 29:256–259

    CAS  PubMed  Google Scholar 

  8. Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:307–310

    Article  CAS  Google Scholar 

  9. Huang YC, Chiou WL (1983) Creatinine XII: comparison of assays of low serum creatinine levels using high-performance liquid chromatography and two picrate methods. J Pharm Sci 72:836–837

    Article  CAS  Google Scholar 

  10. Miller WG, Myers GL, Rej R (2006) Why commutability matters. Clin Chem 52:553–554

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The CKiD 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 (UO1-DK-66143, UO1-DK-66174, UO1-DK-66116). The CKiD Web site is located at https://doi.org/www.statepi.jhsph.edu/ckid. The clinical coordinating centers (principal investigators) are at Children’s Mercy Hospital and the University of Missouri – Kansas City (Bradley Warady, M.D.) and Johns Hopkins School of Medicine (Susan Furth, M.D., Ph.D.), and the data coordinating center (principal investigator) is at the Johns Hopkins Bloomberg School of Public Health (Alvaro Muñoz, Ph.D.), with the Central Biochemistry Laboratory at the University of Rochester (George J. Schwartz, M.D.). We are grateful to Ms. Paula Maier of the CBL for her excellent assistance in coordinating this study.

Author information

Authors and Affiliations

  1. University of Rochester Medical Center, Rochester, NY, USA

    George J. Schwartz, Tai Kwong & Brian Erway

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

    Bradley Warady & Stanley Hellerstein

  3. Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Lori Sokoll & Susan Furth

  4. University of Florida, Gainesville, FL, USA

    Vikas Dharnidharka

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

    Alvaro Muñoz

  6. Pediatric Nephrology, University of Rochester Medical Center, Box 777, 601 Elmwood Avenue, Rochester, NY, 14642, USA

    George J. Schwartz

Authors
  1. George J. Schwartz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tai Kwong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian Erway
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bradley Warady
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lori Sokoll
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Stanley Hellerstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Vikas Dharnidharka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Susan Furth
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alvaro Muñoz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George J. Schwartz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schwartz, G.J., Kwong, T., Erway, B. et al. Validation of creatinine assays utilizing HPLC and IDMS traceable standards in sera of children. Pediatr Nephrol 24, 113–119 (2009). https://doi.org/10.1007/s00467-008-0957-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-008-0957-0

Keywords

Search

Navigation