Enzymatic assays for creatinine: time for action International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) IFCC Scientific Division

Accurate serum creatinine measurements in glomerular filtration rate estimation (eGFR) using equations are critical to ongoing global public health efforts to improve the diagnosis and treatment of chronic kidney disease. There is now an ongoing activity to promote worldwide standardization of methods to determine creatinine together with the introduction of a revised eGFR equation appropriate for use with standardized creatinine methods. Standardization of calibration, i.e., implementation of calibration traceability to high-order reference measurement procedures and reference materials, does not, however, correct for analytical interferences of field methods The exclusive for all languages and countries is vested 1) in the International Federation of Clinical Chemistry and Laboratory Medicine. This paper was commissioned by IFCC, but it does not 2) carry any official endorsement by IFCC. IFCC Sections printed in J. Clin. Chem. Clin. Biochem. are 3) listed in the Cumulative Index, which appeared in connection with the contents of this journal in Volume 27, 1989 and since 1991 have been printed in (Eur.) J. Clin. Chem. Clin. Biochem. IFCC 1991/1 Vol. 29, 435–457 IFCC 1991/2 Vol. 29, 531–535 IFCC 1991/3 Vol. 29, 577–586 IFCC 1991/4 Vol. 29, 767–772 IFCC 1992/1 Vol. 30, 901–905 IFCC 1994/1 Vol. 32, 639–655 IFCC 1995/1 Vol. 33, 247–253 IFCC 1995/2 Vol. 33, 399–404 IFCC 1995/3 Vol. 33, 623–625 IFCC 1995/4 Vol. 33, 627–636 IFCC 1995/5 Vol. 33, 637–660 IFCC 1997/1 Vol. 35, 317–344 IFCC 1997/2 Vol. 35, 345–349 IFCC 1997/3 Vol. 35, 805–831 IFCC 1997/4 Vol. 35, 833–843 For IFCC sections printed in Clin. Chem. Lab. Med. since 1998, please visit the link http://www.atypon-link.com/WDG/ loi/cclm, where they are freely accessible. *Corresponding author: Prof. Mauro Panteghini, Laboratorio Analisi Chimico-Cliniche, Ospedale Luigi Sacco, Via GB Grassi, 20157 Milano, Italy Phone: q39-02-39042806, Fax: q39-02-50319835, E-mail: [email protected] Received for publication December 28, 2007; previously published online February 26, 2008 (non-specificity bias). To account for the sensitivity of alkaline picrate-based methods to non-creatinine chromogens, some manufacturers have adjusted the calibration to minimize the pseudo-creatinine contribution of plasma proteins, producing results more closely aligned to the reference method (isotope dilution-mass spectrometry), but this strategy makes an assumption that the non-creatinine chromogen interference is a constant among samples, which is an oversimplification. Thus, analytical non-specificity for substances found in individual patient samples can affect the accuracy of eGFR computed from serum creatinine values for any alkaline picrate method, including the so-called ‘‘compensated’’ Jaffé methods. The use of assays that are more specific for serum creatinine determination, such as those based on enzymatic reactions, may provide more reliable eGFR values. Supporting the choice of more specific assays by clinical laboratories represents one of the main tasks of our profession in order to achieve the ultimate clinical goal, which is to routinely report an accurate eGFR in all the pertinent clinical situations. Clin Chem Lab Med 2008;46:567–72.