OPTIMIZING GLOMERULAR-FILTRATION RATE AND EFFECTIVE RENAL PLASMA-FLOWMEASUREMENTS USING A SIMPLE PHARMACOKINETIC MODEL

We applied an open one compartment pharmacokinetic model for the deter mination of glomerular filtration rate (GFR) and effective renal plasm a flow (ERPF) based on a rapid intravenous loading dose followed by a constant infusion of I-125-iothalamate and I-131-orthoiodohippurate in order to ensure constant plasma levels of the two clearance markers. The loading dose was based on the assumption that the volume of distri bution of the two markers equals the extracellular volume (25% of the body weight). The infusion rate as calculated after the clearance of t halamate was estimated from body weight, age, sex and serum creatinine using Cockcrofts formula. The clearance of hippurate was assumed to b e four times that of thalamate. We studied the reliability of this mod el in 212 patients with insulin dependent diabetes mellitus (IDDM; n = 74), nephrotic syndrome (NS; n = 18) and heart (HTX; n = 69) or kidne y (KTX; n = 51) transplants. A steady state concentration was obtained in all patient groups, even when GFR was markedly depressed. In patie nts with diabetes, we observed more variance between plasma and urinar y clearances of thalamate, which could be due to inaccuracies in urine sampling. In these patients, GFR should be measured using a method th at is not dependent on urine collection. Also, the estimation of GFR b y means of Cockcrofts equation seems to underestimate GFR in diabetic subjects.