Historically, serum creatinine was analyzed from a blood sample using a method called alkaline picrate. In addition to creatinine molecules, though, it also “counted” non-creatinine molecules that falsely elevated the resulting value by as much as 20%. This assay method was used for decades in the development of creatinine clearance estimates, such as the Cockcroft-Gault method.
Within the past 10-15 year, however, laboratories have largely moved to a new assay called IDMS (isotope dilution mass spectrometry). This method does not detect the non-creatinine molecules, which means that the IDMS value is often 10-20% lower than the more conventional assay. Because older equations, like Cockcroft-Gault, were created and validated using a non-IDMS assay, this poses a problem for estimating creatinine clearance (a surrogate for glomerular filtration rate) when using an IDMS-based lab assay.