Enzymatic assays for creatinine : time for action

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 (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.