Journal of Nephrology

, Volume 27, Issue 5, pp 467–475 | Cite as

Calibration and precision of serum creatinine and plasma cystatin C measurement: impact on the estimation of glomerular filtration rate

  • Pierre DelanayeEmail author
  • Etienne Cavalier
  • Jean-Paul Cristol
  • Joris R. Delanghe


Serum creatinine (SCr) is the main variable for estimating glomerular filtration rate (GFR). Due to inter-assay differences, the prevalence of chronic kidney disease (CKD) varies according to the assay used, and calibration standardization is necessary. For SCr, isotope dilution mass spectrometry (IDMS) is the gold standard. Systematic differences are observed between Jaffe and enzymatic methods. Manufacturers subtract 0.30 mg/dl from Jaffe results to match enzymatic results (‘compensated Jaffe method’). The analytical performance of enzymatic methods is superior to that of Jaffe methods. In the original Modification of Diet in Renal Disease (MDRD) equation, SCr was measured by a Jaffe Beckman assay, which was later recalibrated. A limitation of this equation was an underestimation of GFR in the high range. The Chronic Kidney Disease Epidemiology (CKD-EPI) consortium proposed an equation using calibrated and IDMS traceable SCr. The gain in performance was due to improving the bias whereas the precision was comparable. The CKD-EPI equation performs better at high GFR levels (GFR >60 ml/min/1.73 m2). Analytical limitations have led to the recommendation to give a grade (>60 ml/min/1.73 m2) rather than an absolute value with the MDRD equation. By using both enzymatic and calibrated methods, this cutoff-grade could be increased to 90 ml/min/1.73 m2 (with MDRD) and 120 ml/min/1.73 m2 (with CKD-EPI). The superiority of the CKD-EPI equation over MDRD is analytical, but the precision gain is limited. IDMS traceable enzymatic methods have been used in the development of the Lund–Malmö (in CKD populations) and Berlin Initiative Study equations (in the elderly). The analytical errors for cystatin C are grossly comparable to issues found with SCr. Standardization is available since 2011. A reference method for cystatin C is still lacking. Equations based on standardized cystatin C or cystatin C and creatinine have been proposed. The better performance of these equations (especially the combined CKD-EPI equation) has been demonstrated.


Calibration Creatinine Cystatin C Glomerular filtration rate 


Conflict of interest

The authors declare that there is no conflict of interest.


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Copyright information

© Italian Society of Nephrology 2014

Authors and Affiliations

  • Pierre Delanaye
    • 1
    Email author
  • Etienne Cavalier
    • 2
  • Jean-Paul Cristol
    • 3
  • Joris R. Delanghe
    • 4
  1. 1.Department of Nephrology-Dialysis-TransplantationUniversity of LiègeLiègeBelgium
  2. 2.Department of Clinical ChemistryUniversity of LiègeLiègeBelgium
  3. 3.Department of BiochemistryUniversity of Montpellier 1MontpellierFrance
  4. 4.Department of Laboratory MedicineGhent University HospitalGhentBelgium

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