Clearance kinetics of solutes used to measure glomerular filtration rate

Agents used to measure glomerular filtration rate (GFR) give a biexponentia l plasma disappearance curve on multiple peripheral venous sampling between 20 min and 4 h after intravenous injection. These two exponentials are gen erally regarded to represent equilibration of agent throughout the extracel lular fluid (ECF) space and renal clearance, respectively. In seven subject s undergoing diagnostic arteriography, arterial and antecubital venous plas ma samples were obtained up to 60 min in five and up to 120 min in two foll owing simultaneous intravenous injection of Tc-99(m)-diethylene triamine pe ntaacetate (Tc-99(m)-DTPA) and inulin. The count rate from Tc-99(m) was sim ultaneously recorded over the calf with a collimated scintillation probe in five subjects up to 60 min post-injection. The arterial and venous time-co ncentration curves were interpolated and subtracted to give a curve of the arterio-venous (A-V) concentration difference, which was then integrated. A rterial time-concentration curves display three exponentials, the first of which has the largest amplitude and disappears by about 20 min. The A-V con centration difference becomes zero at about the same time. The integral of the A-V concentration difference, which represents activity in the intersti tial space of the forearm, has a time course consistent with the second com partment of a model of two compartments in series (the first being plasma) and a time course that is reciprocally similar to the first exponential of the triexponential arterial plasma curve. The curve externally recorded by scintillation probe has a shape consistent with a signal that is the compos ite of interstitial Tc-99(m)-DTPA and plasma Tc-99(m)-DTPA activities. The arterial plasma clearance curve of GFR agents is triexponential; the first exponential reflects equilibration of agent between plasma and the intersti tial space of carcass tissue (mainly muscle and skin). The second exponenti al is minor compared with the first; it is not clear what it represents. Th e third exponential reflects renal clearance. ((C) 1999 Lippincott Williams & Wilkins).