Appropriate corrections to glomerular filtration rate and volume of distribution based on the bolus injection and single-compartment technique.
The bolus injection, single-compartment technique for measuring GFR overestimates the true value. Nevertheless, assuming that for a given indicator the area under the first exponential of the plasma clearance curve is constant from subject to subject, the observed (uncorrected) value can be corrected by multiplication with a 'sliding' factor, the value of which is a nonlinear function of GFR. Several second-order polynomials, based on pre-determined relationships between simultaneously determined two-compartment and one-compartment GFR, have been described for correcting GFR (GFR correction). It is, however, theoretically more rational to use a factor which depends on the rate constant, alpha2, of the terminal exponential of the clearance curve. We have therefore determined a set of linear equations from retrospectively analysed multiple-sample inulin, 99mTc-DTPA and 51Cr-EDTA clearance curves to enable correction of GFR using alpha2. A set of linear equations is also developed to correct the volume of distribution (Vd) of the indicator (close to extracellular fluid volume for these indicators), which is also overestimated by the one-compartment technique. At low levels of GFR, alpha2-corrected GFR is similar to uncorrected GFR for all three indicators. As GFR increases, however, uncorrected GFR progressively overestimates (alpha2-corrected GFR. The overestimation is greater for inulin than for 99mTc-DTPA or 51Cr-EDTA. In the one-compartment approximation, Vd is overestimated more than GFR, and again the greatest overestimation is seen with inulin. In a prospective study of 129 patients undergoing routine measurement of GFR with 51Cr-EDTA, alpha2 correction using a factor based on retrospective EDTA data gave values of GFR which were higher than values obtained from GFR correction using a previously published polynomial (also based on EDTA clearances) by 15% in children and 12.5% in adults when uncorrected GFR was 150 ml/min/1.73 m2. Moreover, the ratio of uncorrected GFR to GFR-corrected GFR was higher in children than adults. We conclude that alpha2 is a more rational variable with which to correct two-sample or three-sample GFR than GFR itself, that the correction formulae are not interchangeable between inulin on the one hand and EDTA and DTPA on the other, and that the relative magnitudes of the corrections given by alpha2 correction versus GFR correction are different for children and adults.