Comparison between terminal slope rate constant and "slope/intercept" as measures of glomerular filtration rate using the single-compartment simplification

Several whole-body variables are available for indexing,glomerular filtrati on rate (GFR), including extracellular fluid volume (ECF volume, ECV), whic h has the advantage that GFR based only on the terminal exponential, alpha (2), of the chromium-51 ethylene diamine tetraacetic acid (Cr-51-EDTA) plas ma clearance curve is a measure already indexed for ECV. This slope-only me thod, however, is open to the theoretical criticism of a lack of robustness not present in the more conventional slope/intercept method, which generat es GFR in absolute units before indexation to body surface area (BSA). To f urther evaluate the slope-only method, a large database of routine three-sa mple GFR measurements, based on Cr-51-EDTA, was analysed with the aim of co mparing GFR/BSA with GFR/ECV, identifying the main sources of error in thei r respective measurements and explaining why they might be discrepant. The database was subdivided into 304 patients (group A) in whom the correlation coefficient of the fit to the three data points was greater than 0.99 and 31 patients in whom it was less than 0.99 (noisy data; group B). There was modest agreement between GFR/BSA and GFR/ECV in group A (r=0.77; mean ratio 1.01 +/-0.21). The difference between them correlated significantly with B SA (r=0.52; P<0.001), as would be expected given that small individuals hav e a relatively high BSA. Subdividing group A into four subgroups stratified according to BSA led to a slight improvement in the correlation between GF R/BSA and GFR/ECV. Because an error in a, is balanced by an opposing error in the intercept (which leads to a change in distribution volume in the opp osite direction), and therefore impacts on both GFR/BSA and GFR/ECV, wherea s an error in administered dose affects only GFR/BSA, it is possible to eva luate such errors by examining the respective relationships of GFR/BSA and GFR/ECV with indexed ECV. In group A, GFR/BSA correlated positively with EC V/1.73 m(2), not surprisingly as ECV/BSA is effectively the ratio GFR/BSA t o GFR/ECV, while GFR/ECV correlated negatively with ECV/1.73 m(2). This imp lies that errors other than <alpha>(2) probably principally in administered dose, were as important as errors in alpha (2). This conclusion was suppor ted by disappearance of the positive correlation between GFR/BSA and ECV/BS A in group B, brought about by the greater errors in alpha (2) in this grou p. This study suggests that, because of the effects of errors in the slope/ intercept method that do not affect alpha (2) GFR based on slope only is at least as robust as that based on slope/intercept.