SINISTRIN CLEARANCE FOR DETERMINATION OF GLOMERULAR-FILTRATION RATE -A REAPPRAISAL OF VARIOUS APPROACHES USING A NEW ANALYTICAL METHOD

Several approaches are available to estimate the glomerular filtration rate (GFR) from the sinistrin clearance. To compare such approaches, GFR was estimated in six healthy volunteers, both after a bolus inject ion and a bolus dose followed by a g-hour infusion. A recently develop ed high-performance liquid chromatography method was used for the dete rmination of sinistrin levels, enabling precise measurements in plasma and urine samples with high sensitivity. Blood and urine were sampled up to 6 hours. Four calculation methods for estimating GFR were appli ed: 1) classical ratio of urinary excretion rate over plasma concentra tion (UV/P); 2) two-point (log-linear regression slope times monocompa rtmental volume of distribution) after bolus; 3) ratio of dose over ar ea under the curve (D/AUC) after bolus; and 4) ratio of infusion rate over steady-state concentration during infusion (R-inf/P). The results obtained by fitting a pharmacokinetic model to all the plasma and uri ne data served as the standard against which the performance of the re spective calculation methods were examined. The UV/P method performed poorly on bolus data, mainly by underestimating GFR at late times; on both bolus and infusion data, it suffered from important imprecisions on the urinary volume. The two-point method appeared applicable only b etween 2 and 4 hours after the bolus dose. The D/AUC method with extra polation to infinity was highly reliable when integrating the concentr ations up to 3 hours or more after the bolus dose. The R-inf/P method was satisfactory if applied later than 2 to 3 hours after the loading dose. The advantages and drawbacks of each method have to be evaluated in relation to the particular clinical setting in which GFR is to be estimated.