Comparison of the Constant Infusion and Urine Collection Techniques for the Measurement of Renal Function 1

Abstract

For any exogenous substance which is neither metabolized, stored nor excreted otherwise than in the urine, the rate of excretion must be equal to the rate of infusion under conditions where its plasma level and volume of distribution are constant. This steady state, as indicated by a constant plasma level, will be designated infusion equilibrium.A simplified method for the measurement of glomerular filtration rate and the effective renal plasma flow based upon the above principle has been described elsewhere (1). In the application of the principle, the rate of infusion, IV (where I is the concentration in mg. per ml. of infusion fluid and V is the volume of fluid injected in ml. per minute), can be substituted for the rate of excretion, UV, in the clearance calculation, i.e., IV/P = UV/P. The procedure, therefore, obviates the necessity of bladder catheterization and the errors inherent in urine collection. bladder rinses with water and air. The maximum rate of excretion of PAH by the tubules (TmPaH) was also measured in some of the experiments (3). Three or more serial urine collection periods of 15 to 30 minutes each were measured. Priming injections of inulin and PAH were given intravenously in amounts calculated to achieve plasma levels of 5 to 20 and 2 to 3 mg. per cent respectively. The approximate volume of distribution for an average normal subject was taken as 15 liters for inulin and 20 liters for PAH. Priming injections of 2 grams of inulin and 0.8 gram sodium p-aminohippurate were frequently used and generally resulted in plasma levels of 10 to 15 and 2.5 to 3.0 mg. per cent respectively. Priming doses were modified for persons of unusual size, and were greatly increased in the presence of edema.The sustaining infusions were delivered by a pump at a rate calculated, on the basis of estimated renal function, to maintain the desired plasma concentrations. For example, if the estimated filtration rate was 100 ml. per minute and if the plasma inulin concentration desired, and presumably achieved by the priming injection, was 5 mg. per cent then each minute 100 X 0.05 or 5 mg. would be excreted in the urine. The sustaining infusion, therefore, would deliver 5 mg. of inulin per minute.For Tmpma measurements the desired plasma PAH level was roughly calculated for a load/Tm ratio of 2 from the equation:Plasma PAH level X renal plasma flow (measured or estimated) Anticipated TmPAHThe priming PAH dose was calculated from the desired plasma PAH level and a volume of distribution of 20 liters for the individual of average size. The estimated plasma PAH level was substituted in the formula (3): Anticipated TmPAH =UV -0.83 CINPPAH, where CIN represents the anticipated inulin clearance.The equation was solved for the term UV which represents the amount of PAH excreted in the urine per unit of time and, therefore, the amount which must also be delivered by the sustaining infusion.The infusion pump used in the early experiments consisted of a worm-drive rod powered by a constant speed motor that pushed on the plunge...

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