Pitfalls of single-sample determination of renal clearance

Single-sample techniques are widely used for determination of renal clearance by elimination kinetics of radiolabelled marker substances. Frequently, however, formulae for transforming single-time measurement values into estimates of kinetic function, such as renal clearance, are being established exclusively by data reduction methods and are devoid of any physiological meaning.

Using 11 subjects with normal or impaired renal function, we compared one such method using (99m)Tc-labelled mercaptoacetyltriglycine ((99m)Tc-MAG(3)) for single-sample determination of tubular extraction rates with a more elaborate computer-based system identification technique. This latter method yields measures for glomerular filtration rate as well as effective renal plasma flow based on elimination kinetics of sinistrin and p-aminohippuric acid.

When applying the single-sample technique, two of the 11 estimated values for tubular extraction rate were negative, indicating an erroneous analysis of kinetic behaviour. This single-sample method failure was not caused by the marker, but rather by the specific mathematical procedure used for the evaluation. Importantly, evaluation of the same experimental data with a conventional two-sample technique would eliminate the principal mathematical defect and produce physiologically reasonable results, without requiring additional effort.

Our study does not criticize the (99m)Tc-MAG(3) technique per se. Rather, these findings indicate that usage of single-sample techniques for determination of inherently kinetic phenomena may produce incorrect results. Therefore, despite their obvious practical advantages, such simplified methods should be performed with great caution.