The Secretory Function of the Renal Tubules

The Renal Excretion of Creatinine in Man

“…This result leads, of course, to a reduction in the rate of excretion relative to plasma level, the phenomenon described in the first part of the paper. As Marshall and Crane (1924) pointed out in their discussion of the excretion of phenol red by the dog, a curvilinear relationship between plasma level and rate of excretion (or, in our present terms, between plasma level and clearance) is incompatible with exclusive filtration. It is conceivable that a substance excreted both by filtration and tubular secretion might display a linear relationship in this respect (as in fact creatinine does when the plasma is falling); but we are unable to imagine any' reason why the clearance should decrease with increasing plasma concentration unless secretion is involved.…”

“…Marshall and Grafflin (1932) have shown in the toadfish that the quantity of creatinine excreted per unit time does not increase in direct proportion to the quantity injected into the body. This failure to obtain direct proportionality between the quantity of substance administered and the rate of its excretion was first described for any substance by Marshall and Crane (1924) in their examination of the excretion of phenol red by the dog, and these investigators pointed out that the observed curvilinear relationship between plasma level and rate of excretion was incompatible with excretion by exclusive filtration. A similar phenomenon has subsequently been shown by Bieter (1933) and Marshall and Grafflin (1932) to occur in the excretion of phenol red in the toadfish.…”

The Excretion of Inulin, Xylose and Urea by Normal and Phlorizinized Man 1

“…We previously deemed that this linear relationship did not necessarily exclude secretion (Shannon, Jolliffe and Smith (1932)), because we believed it possible that a secretory mechanism might be able to handle a substance in direct proportion to the plasma concentration. On reconsideration, however, we note that those substances for which there is independent evidence of secretion are found, in fact, to show a curvilinear relationship, i.e., phenol red in dog (Marshall and Vickers (1923); Marshall (1931)), frog (Marshall and Crane (1924)), toadfish (Marshall and Grafflin (1932);Bieter (1933)); creatinine in the toadfish (Marshall and Grafflin (1932)), dogfish (Shannon (1934a(Shannon ( , 1934b), and in man according to evidence to be presented later. In theory, it would seem that any process of secretion, involving as it does the expenditure of energy in work, might be diminished, relative to the plasma level, at high'plasma concentrations, and consequently that the amount excreted per unit time would be related to the plasma level in a curvilinear manner (Shannon (1934a)).…”

The state in the blood and the excretion by the kidney of the antidiuretic principle of posterior pituitary extracts

“…Thus as the amount of hormone injected is increased, the proportion of the hormone which is excreted in the urine decreases (see Table IV There seems to be no other instance of a similar excretory mechanism for a physiologically active non-foreign substance, but an interesting parallel can be found in the urinary elimination of certain organic dyes, especially phenol red. These seem to be adsorbed by the colloids of the blood and liberated by the kidney in much the same manner as the, antidiuretic hormone of the pituitary gland [Marshall & Vickers, 1923;Marshall & Crane, 1924;Grollman, 1925;Bennhold, 1932;Shannon, 1935;Goldring et al 1936].…”