On the Renal Tubular Excretion of Creatinine in Normal Man1

Abstract

The demonstration that in man the renal excretion of exogenous creatinine 1 takes place in part by an active tubular process depends upon two experimental findings (1). The plasma clearance of creatinine in the normal individual is invariably in excess of the simultaneously determined inulin clearance, which is accepted as a valid measure of glomerular filtration rate (2). Furthermore, raising the plasma creatinine from low to high concentrations depresses its clearance toward that of inulin, which appears to be its limiting value. However, contrary to similar findings in the dogfish (3) and chicken (4), this depression is not completely reversible.More recently, both the presence and the significance of the curvilinear relationship between plasma concentration and renal excretion of creatinine have been questioned. Winkler and Parra (5) observed that, following the ingestion of a single dose of creatinine, its clearance and the creatinine/sucrose clearance ratio behave rather erratically, but are generally depressed as the experiment progresses. These authors believe that the curvilinear relationship, as previously described, is not a dependent one. They suggest that its presence in the original experiments was incidental to an experimental routine which usually resulted in the high plasma concentrations being observed later than the low ones. Findley (6) later re-examined the relationship between plasma concentration and renal excretion over a range of plasma values of 1.0 to 14.0 mgm. per cent. His findings are precisely the same as those previously reported by Cope (7). That is, a linear relationship between these two variables obtains if one arbitrarily corrects the observed plasma concentration by -0.5 mgm. per cent of assumed non-creatinine chromogenic material. He did not consider the depression of the creatinine 1 In this report, unless specifically stated to the contrary, the term creatinine may be taken to mean exogenous creatinine.clearance at higher plasma levels valid evidence of tubular excretion, since the concentrations necessary to demonstrate the phenomenon were " far beyond the physiological range." The linear relationship limited to the lower plasma values was then advanced as evidence opposing the renal tubular excretion of creatinine. This conclusion would favor Rehberg's (8) original contention that creatinine is excreted solely by glomerular filtration.More recently, Rehberg (9) has called attention to the demonstration by Abdon (10) that the administration of creatinine leads to the appearance in the plasma of a substance resembling creatinphosphoric acid. It is Rehberg's belief that the tubules do not participate in the excretion of preformed creatinine but rather that they may transfer creatinine which has its origin in the plasma in some more complex compound, such as that described by Abdon. This is an important consideration, since this type of compound would yield true creatinine in ordinary plasma filtrates and behave as suclh toward both specific and nonspecific analytical metho...

DEPRESSION OF THE EXOGENOUS CREATININE/INULIN OR THIOSULFATE CLEARANCE RATIOS IN MAN BY DIODRAST AND p-AMINOHIPPURIC ACID 1

“…This conclusion extends the evidence for the tubular excretion of creatinine as advanced by Shannon (21) and Shannon and Ranges (27), and confirms that reviewed elsewhere on the mechanism of excretion of inulin (39).…”

“…Shannon and Ranges (27) have, however, presented evidence to refute this view. They have shown that (a) the creatinine/inulin clearance ratio does not fall markedly with time if the plasma level is maintained by the continuous infusion of creatinine, (b) a second dose of creatinine elevates the clearance ratio, after this has been depressed by the lapse of time, towards the values observed shortly after a first dose, and (c) this elevation occurs only if the ratio has been depressed by virtue of the prolonged circulation of creatinine in the body.…”

Cardiovascular, Renal, and General Effects of Large, Rapid Plasma Infusions in Convalescent Men 1

“…The PAH clearance, without an extraction correction factor, was used to measure changes in renal plasma flow. As facilities for inulin or mannitol clearances were not available, creatinine clearance was used as a reflection of glomerular filtration, although it is generally felt that inulin or mannitol better measure this in man (31,32). Creatinine/inulin ratios recently published (33,34) suggest, however, that creatinine clearance is a fairly good measure of glomerular filtration, especially when PAH or diodrast is administered concurrently.…”

The Use of Inulin Clearance as a Measure of Glomerular Filtration

“…Shannon and Smith [1935] claimed to establish the constancy of the renal clearance of inulin between plasma inulin levels of 50 and 400 mg./100 ml. Since extrapolation of the straight line which they constructed, relating the renal excretory rate of inulin and the corresponding plasma levels, passed through the point of origin, they concluded that the independence of inulin clearance and plasma levels still persisted at plasma levels below 50 mg./100 ml., and that the slope of the regression line represented the rate of glomerular filtration.…”