The Use of Inulin Clearance as a Measure of Glomerular Filtration

Abstract

1. Following a single intravenous injection of inulin, values for the renal clearance of inulin (Cin = µν/P) show a steady decline, with diminishing values of plasma inulin concentrations. 2. Employing values of P 6 minutes before the mid‐point of the clearance period, in place of values 2½‐minutes before the mid‐point, does not eliminate this phenomenon. 3. Employing the formula Cin = µν/P, the fall in values for clearance is due to the fact that the renal excretion of inulin (µν) is not proportional to the plasma level (P), since the imposition of a linear relationship between the two variables results in lines which deviate significantly from the point of origin. 4. The lack of proportionality is shown not to be due to the sampling of venous blood as an estimate of arterial plasma inulin concentrations. 5. The dependence of the magnitude of the renal clearance of inulin upon the plasma concentration of inulin is found also in three subjects using the continuous infusion method of administration. This excludes the possibility that the results obtained, following a single injection of inulin, are distortions of a simple proportional relationship consequent upon the dynamics of distribution of inulin in the body following a single injection. 6. The results of the experiments, and those of other workers, are held to suggest strongly that, in man, inulin is reabsorbed by the tubules to a significant extent. Hence the use of inulin clearance as a measure of glomerular filtration rate involves a systematic error, which is estimated to be about 15 per cent. under the usual circumstances.

Measurement of Glomerular Filtration Rate in Children With Kidney Disease 12

“…Rather, the curve would, when extrapolated, intersect the ordinate at a negative value. Contrary to these and the earlier results mentioned (8, 23), Ferguson and his associates (24) have recently reported observations in which lines similarly plotted did intersect the ordinate at a negative value, from which they conclude that tubular reabsorption of inulin occurs. However, in their four observations in three subjects to whom continuous intravenous infusions of inulin were given, the inulin was dissolved in physiologic saline and different serum inulin concentrations were achieved by changing the rate of infusion rather than by changing the concentration of inulin in the infusion fluid as done here.…”

The Relationship Between the Clearance and the Plasma Concentration of Inulin in Normal Man

“…Accordingly, the average of successive periods is likely to reflect this error less than the single period in which the acute change occurred. In fact, it may be seen from Table III that when the average of three successive periods at one plasma level of inulin is compared to the average of all (usually nine) periods for any individual, the variability is much smaller than that estimated by Smith and by others (3).…”

“…Both groups considered that this constituted important evidence that inulin clearance measured the rate of glomerular filtration. Recently, Ferguson, Olbrich, Robson, and Stewart (3) presented data showing that the rate of excretion of inulin was not directly proportional to its concentration in plasma, and that the clearance of inulin was dependent upon the concentration of this substance in plasma.…”

Laboratory Aids to Diagnosis and Therapy

“…Inulin has many properties to recommend it as a measure of glomerular filtration and has, almost by common consent, been accepted as the yardstick for the evaluation of purely filtrable substances; but some of the evidence on which its use for this purpose is based is purely inferential. Robson, Ferguson et al (168,169) have recently adduced evidence that as much as 15 per cent of the inulin that passes through the glomerular filter may be reabsorbed from the renal tubules. They have also directed attention to the fact that clearances of inulin, like those of exogenous creatinine and certain other substances, vary according to the conditions under which they are measured, diminishing when the concentration of inulin in the serum is faIling.…”