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Nine models were evaluated as candidate glomerular filtration rate (GFR)reference standards in three datasets using [$^{51}$Cr(EDTA)]$^-$ or[$^{169}$Yb(DTPA)]$^{2-}$ anions in 98 studies. Noncompartmental methods formedan upper limit for estimating mass excreted and voluntary urine collectionformed a lower limit. For current models and methods, reduced GFR in adultsresulted in inflated clearance estimates. Two different logarithmic models withexponential tails were created and may have underestimated reduced clearance.The logarithmic formulae can be used with only two plasma samples, and fit 13studies totalling 162 plasma samples drawn from 5 min to 24 h with an 8%standard deviation of residuals compared to 20% error for monoexponentials. Forshorter times (4 or 5 h) the fit errors decreased but the ratio of errorsremained at circa 2.5 times lesser for the logarithmic versus monoexponentialmodels. Adaptively regularised gamma variate, Tk-GV, models that are welldocumented, but not in common use, were largely contained within the referenceextreme values, were unbiased for different levels of clearance and were theonly models to be uncorrelated to volume of distribution from mean residencetime divided by weight. Using Tk-GV as a candidate reference standard,potentially better methods for routine clinical usage were discussed.Prospective clinical testing, and metabolic scaling of decreased renal functionis advised for potential changes to patient triage.

scandinavian journal of clinical and laboratory investigation

Reference standard analysis of multiple new and old plasma clearance  models and renal clearance with special attention to measurement of reduced  glomerular filtration rate