Enzymatic assays for creatinine: Time for action

Estimation of glomerular filtration rate (eGFR) on the basis of serum creatinine concentration measurements using equations is critical to ongoing global public health efforts to improve the diagnosis and treatment of chronic kidney disease. There is now ongoing activity to promote world-wide standardization of methods to measure creatinine concentrations, together with the introduction of a revised eGFR equation appropriate for use with standardized creatinine methods. Standardization of calibration, i.e. implementation of calibration traceable to higher-order reference measurement procedures and reference materials, does not, however, correct for analytical interferences of field methods (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, thereby producing results more closely aligned with the reference method (isotope dilution-mass spectrometry), but this strategy makes the assumption that the non-creatinine chromogen interference is constant among samples, which is an oversimplification. Thus, analytical non-specificity for substances found in individual patient samples affects the accuracy of eGFR computed from serum creatinine concentrations for any alkaline picrate method, including the so-called "compensated'' Jaffe methods. Using assays that are more specific for serum creatinine, such as those based on enzymatic reactions, may provide more reliable eGFR values. Supporting the choice of more specific assays by clinical laboratories is one of the main tasks of our profession in achieving the ultimate clinical goal, which is to routinely report an accurate eGFR in all pertinent clinical situations.