The standard method of estimating the rate of glomerular filtration
(G.F.R.) in man has been by the renal clearance of inulin since it was
demonstrated. that this plant polysaccharide is neither secreted nor reabsorbed by the renal tubules. The criteria which must be satisfied
by a substance for its renal clearance to cive a valid measure of glomerular filtration rate have been discussed in detail by Smith (1951).
Chemical methods for the determination of inulin in plasma and urine
have been rather unsatisfactory (Smith 1951) and a variety of substances
have been studied in an attempt to find a substitute for inulin. The
endogenous creatinine clearance is widely used for clinical purposes but
the creatinine/inulin clearance ratio exceeds unity in many human
subjects indicating a variable deree of tubular secretion of creatinine
(Smith 1 951 , Berlune et al 1 964) and this clearance is not a reliable
measure of glomerular filtration in man.Recently a number of compounds labelled with radioisotopes have
been studied and found to have clearances similar to'that of inulin.
Allyl inulin labelled with ¹²⁵I has a clearance virtually identical to
that of inulin in the dog (Concannon et al 1964) but is not readily
available and is difficult to sterilise. Radioactive ⁵⁷Co-labelled
cyanocobalamin gives a satisfactory measure of G.F.R. if only the free
vitamin in the plasma is measured (Nelp et al 1964, Cutler and Glatte 1965).
However, even after a large loading dose of unlabelled cyanocobalamin,
plasma protein binding, of the labelled compound occurs and is variable
in extent, nor is it easy to determine the proportion. of the labelled vitamin which is plasma bound in vivo (Skins and Sgherzi 1964,
Donaldson and Doig unpublished observations). The most convenient
inulin substitutes so far available are .the radiographic contrast media
sodium diatrizoate ( Hypaque) and meglumin diatrizoate (Renografin)
labelled with ¹³I or ¹²⁵I. In man Hypaque appears to fulfil many of
Smith's criteria, it is not significantly bound to plasma proteins
(Lasser et al 1962) nor does it readily penetrate red blood cells
(Denneberg et al 1961), its renal excretion is complete and its extrarenal excretion negligible (Denneberg 1965). Hypac,ue and Renografin
have been shown by various authors to have clearances very similar to
the simultaneous inulin or thiosulphate clearance in man and the
literature on these compounds has been well reviewed by Denneberg (1965).
However some authors have not found the Hypaque and inulin or thiosulphate clearances to be identical (Bianchi and Zampieri 1961, Woodruff
and Malvin 1560, Stokes et al 1 ;62, Denneberg 1565 and while some comparisons were carried out during continuous infusion of inulin and
Hypaque (Burbank et al 1963), others were made on the basis of a single
injection of Hypaque (Bianchi and Zampieri 1961). The latter are difficult
to interpret physiologically; the difficulties inherent in all "single
injection" clearances have been discussed by Smith (1951) and Robson et
al (1949) .It has been variously suggested that Hypaque is neither reabsorbed
nor secreted by the renal tubules in man (Burbank et al 1963), nor in
the dog Woodruff and Malvin 1960), that it is reabsorbed in man (Bianchi and Zampieri 1961) and in dog (Stokes et al 1962) and that it is
both secreted and reabsorbed in man (Denneberg 1965).Morris et al (1965) found that the clearance of ¹³¹I Renografin
did not alter when the plasma level was raised by large doses of inactive
Renografin, suggesting that this compound is not handled by the tubules.
However they studied only two subjects in this way. Hypaque would be
expected to behave in the renal tubules in the same way as Renografin
as it is the diatrizoate ion which is estimated in both cases. However
Denneberg (1965) found that the Hypaque /inulin clearance ratio fell, on
average, after the administration of the tubular blocking agent probenecid
and concluded that Hypaque is secreted and perhaps also reabsorbed by the
renal tubules in man.Because of this confusion in the literature about tubular handling
of Hypaque in man, the studies described in this paper were carried out
in an attempt to resolve the Question of whether or not radioactive
labelled Hypaque is handled by the renal tubules and to investigate its
clearance as a measure of the rate of glomerular filtration in human
subjects
