1967, Br. J.

Radiol, 40, 561-580

VOLUME 40 NUMBER 476

AUGUST 1967

The British Journal

of Radiology
Excretion urography
IFactors determining the excretion of Hypaque
By W. R. Cattell, M.D., M.R.C.P.,1. Kelsey Fry, D.M., M.R.C.P., F.F.R., A. G. Spencer, M.D., F.R.C.P.,
and P. Purkiss, B.Sc, Grad.R.I.C.
Medical Professorial Unit and Department of Radiology, St. Bartholomew's Hospital, London, E.C.1
Since the introduction of excretion urography
(IVP) by Swick in 1929, this procedure has gradually been improved and is now indispensable in
the diagnosis of renal disease. The greatly increased reliability and widespread use of the IVP
has three causes: the development of increasingly
radio-dense contrast media (Benness, Bullen and
Barker, 1965; Meschan, 1965); advances in radiographic apparatus and X-ray films; and an increasing awareness of the diagnostic significance of finer
points of morphological detail (Hodson 1962;
Olsson 1963). None the less, the full diagnostic
potential of the IVP is by no means universally or
frequently attained, even in patients with good renal
function. In recent years several new methods for
obtaining better IVPs have been described, such
as infusion (Schencker, 1964; Harris and Harris,
1964), high dosage (Ross, Wilson, Robards and
Thompson, 1964; Amar, 1964; Benness, 1965), and
hydration (Brannan, Birchall, Batson and Kittredge, 1963) techniques. Because of their increased
cost, greater demands on departmental time and the
possibility of additional hazards and toxicity to the
patient, these new methods should not be generally
adopted until they have been fully evaluated and
demonstrated to be superior to existing techniques.
This demands controlled studies of new techniques
or dosage schedules taking into account the numerous independently variable factors which determine
the quality of the pyelogram.
Excluding consideration of factors such as tissue
density, body proportions and X-ray exposure, the
Based on a paper given to the British Institute of Radiology,
March 17, 1966.

opacity of the urogram depends on the number of

radio-dense molecules within the kidney and the
urinary outflow tract. Therefore, while many independent variables affect the quality of the intravenous urogram, the most important of these is
the excretion of the contrast medium by the kidneys. It is the purpose of the present study to reexamine the factors which control the rate and mode
of excretion of a widely employed contrast medium
(sodium diatrizoate, "Hypaque 45" subsequently
referred to as Hypaque) in order to establish the
physiological basis of the quantitative aspects of
urography. Previous experimental work (Keates,
1953; Harrow, 1955; Wigh, Anthony and Grant,
1962; Marshall, 1964; Benness et al., 1965) has been
limited by the lack of a satisfactory method for the
estimation of the contrast medium in the blood and
urine. The development in this laboratory of a simple
ultraviolet spectrographic absorption technique for
the measurement of Hypaque (Purkiss, Spencer,
Cattell and Lane) has facilitated the present detailed
studies of its renal excretion. The subsequent analysis and correlation of the functional data with an
objective computation of the diagnostic quality of
the IVP (Fry, Cattell, Spencer and Purkiss,
1967) has led to methods by which high-resolution
urography can be predictably obtained in the
majority of patients.
MATERIAL AND METHODS

Patients
Observations were carried out on consecutive
out-patients referred to the X-ray department for
IVP. Subjects were selected only in so far as

561

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40, No. 476

W. R. Cattell, I. Kelsey Fry, A. G. Spencer and P. Pur kiss

patients previously known to have gross renal

disease were excluded. 223 patients were studied.
For the purpose of the present analysis those patients who were found to have a glomerular filtration
rate (GFR) of less than 60 ml./minute (approx.
50 per cent of normal) and those found to have significant distortion of the renal pelvis and urinary
outflow system were excluded. There remained a
group of 140 patients. There were 69 males and 71
females, the average age being 44 years and the
range 15 to 82 years.
Procedure
The patients were fasted and deprived of fluid
from 6 p.m. the previous evening (14-18 hours).
Subjects emptied their bladder on arrival in the
department and subsequently timed complete urine
collections were obtained immediately before and
45 minutes after the intravenous injection of Hypaque.
Preliminary studies were made in 15 patients
with in-dwelling venous catheters in the contralateral arm, from which blood samples were taken
at intervals of \, 1, 2, 4, 6, 8, 10, 15, 20 and 30 minutes following the injection of Hypaque. From analysis of the time/concentration curves for plasma
Hypaque it was decided to take blood samples from
the main series of patients at 0 and 10 minutes.
One rapid intravenous injection of 20-120 ml.
of 45% Hypaque was given. The patients' height
and weight were measured and recorded, and the
dosage was expressed as ml./m2 body surface and
ml./lb. of body weight.
In 34 patients 80 ml. of 45% Hypaque in 150 ml.
5 per cent Dextrose were administered as a continuous intravenous infusion over a period of ten minutes.
Investigation on normal subjects
Fifteen experiments were performed on normal
healthy male volunteers, deprived of food and
fluids for 14 hours. After voiding, timed complete
urine collections were taken at intervals of ten
minutes for one hour, following a rapid intravenous
injection of Hypaque in a dosage of 0-25, 0-5 and
0-75 ml./lb. body weight. Blood samples were obtained from an intravenous catheter in the contralateral arm at intervals of | , 1, 2, 4, 6, 8, 10, 15, 20,
30, 40, 50 and 60 minutes. In eight of these experiments urine collections were continued up to 24
hours and further blood samples obtained at 3,
6 and 24 hours.
Analytical methods
Hypaque (Purkiss et al.)
Creatinine. Auto-analyser.

Sodium and potassium. Flame photometry.

Urine pH. Radiometer pH meter.
Urine osmolality Fiske osmometer.
Measurements and calculations
In all subjects measurements and calculations
were made of the plasma Hypaque concentration,
the GFR, the rate of water excretion and the concentrations of Hypaque in the urine. In addition,
in the acute experiments estimations were made of
the urine pH osmolality, sodium and potassium
concentration. A complete presentation and analysis of this data is to be published elsewhere (Spencer, Purkis, Fry, Cattell and Lane).
The majority of the subjects studied were dehydrated with low rates of urine flow prior to the
injection of Hypaque. This and the fact that a compression band was applied for a time during the
post-injection study period, obviously introduced
the possibility of collection errors or interference
with renal function. To minimise such a possibility
only those subjects were included in the analysis
in whom the GFR was measured both before and
after the injection of Hypaque and did not differ
by more than 10 per cent.
It is possible to calculate the volume of distribution of Hypaque (Hypaque space) from the
formula:
HD - HE
H D =weight of Hypaque injected
in g.
where
H E =Hypaque excreted in urine
at time T.
Hp
H p =plasma Hypaque concentration at time T.
This may then be expressed as a percentage of
the body weight.
RESULTS

Plasma Hypaque concentration

Figure 1 gives the results of a rapid sequence of
estimations of the plasma Hypaque concentration
in 14 subjects with normal renal function and
matched for body size, following a single intravenous injection of 20,40 or 80 ml. of 45% Hypaque.
The fall in plasma concentration is not a simple exponential function, and on detailed analysis of a
semi-logarithmic plot it is seen to exhibit three distinct phases. In the first there is a very rapid fall in
concentration equivalent to dilution in a volume of
distribution of 2,400 ml., which corresponds to mixing of the Hypaque in the vascular compartment.
The second phase has a slower decline in the plasma
concentration, with an equivalent volume of distribution of 12 1., corresponding to mixing in the

562

AUGUST 1967

Excretion Urography/

500

o400
8 0 ml HYPAQUE

8300

ii

<m

40ml HYPAQUE

to
Q_

100

20 ml HYPAQUE

I
4

10

14 16 18 20 22 24 26 28 30
TIME minutes
FIG. 1.
Mean plasma Hypaque concentrations and range of values obtained following the intravenous injection of 20, 40 and 80 ml. of Hypaque. Figures in parenthesis represent
the number of subjects studied.

12

[5]

12

ml.

o
o

300-

UJ

ID

200-

3ioo-

t
i*

a.

ij.

c.

'
o

10 20 30 40 50 60 70 80

DOSE OF HYPAQUE ml.

FIG. 2
Plasma Hypaque concentration obtained following the intravenous injection of doses 2080 ml. of Hypaque.

extra-cellular fluid. The third phase exhibits a very

gradual fall in the plasma concentration, which if
extrapolated, extends over several hours and is due
to its excretion in the urine. It will be shown later
that, although the renal excretion of Hypaque commences in the first two minutes following the injection, the amount excreted in the first ten minutes accounts for only 12 per cent of the total, and
88 per cent of the fall in plasma Hypaque concentration at that time is due to mixing and dilution in the
plasma and extracellular body fluids. The third phase
of the plasma Hypaque concentration curve is the
result of the renal excretion of Hypaque. The early
rapid fall in plasma Hypaque concentration is
essentially complete at ten minutes, and the value
at this time has therefore been taken in all subsequent patients as a measure of plasma concentration following a single intravenous injection.
Figure 2 gives the ten-minute plasma concentrations of 95 subjects following a single intravenous
injection of 20, 40 or 80 ml. of 45% Hypaque. As
the dose is increased, higher plasma concentrations
are in general obtained, but a wide range of values
is produced at any one dose level. When the same
data are re-plotted with the dose expressed in ml./m2

563

VOL.

40, No. 476

W. R. Cattell, I. Kelsey Fry, A. G. Spencer and P. Purkiss

450

12'

II'
10'
cr
1

->l

Dot 45

Q'

5LU
|

3-

JI00-

250-

'-.' **

-A.';

15

10 15 20 25 30 35 40 45 50 55 60 65
DOSE OF HYPAQUE ml./m 2

100
200
300
400
"FILTERED LOAD" HYPAQUE mq/min

FIG. 3.
Plasma Hypaque level related
to dose of Hypaque expressed
as ml./m2 body surface.

body surface (Fig. 3) an impressive positive linear

correlation is demonstrated (R=0-95). The plasma
concentration of Hypaque at ten minutes is therefore primarily a function of dose and of body size.
It is possible to predict accurately the plasma
concentration which will be obtained by a given
dose. Of more practical importance, the amount
of Hypaque required to produce a given plasma
concentration can be precisely calculated. It should
be noted that this is largely independent of renal
function.
Renal excretion of Hypaque
Figure 4 relates the amount of Hypaque excreted
in the urine in the first 45 minutes following its
intravenous injection to the product of the plasma
Hypaque concentration at ten minutes and the
simultaneously measured glomerular filtration rate
(endogenous creatinine clearance=GFR). The positive linear correlation (R=0.85) demonstrates that
the greater the product GFR X plasma concentration of Hypaque the larger the amount of Hypaque
excreted in the urine. This is in accord with previous studies (Woodruff and Malvin, 1960; Blaufox,
Sanderson, Tauxe, Wakim, Orvis and Owen 1963;
Tauxe, Burbank, Maher and Hunt, 1965; Denneberg, 1964) which have demonstrated that Hypaque
is excreted predominantly by glomerular filtration

FIG. 4.
Hypaque excretion in the urine related to "filtered load'
("Filtered load" = ten-minute plasma level X GFR.)

and that there is no significant tubular reabsorption or secretion of this particular compound.
Figuie 5 records the amount of Hypaque excreted
in the urine following single injections of 0-25,
0-50 and 0-75 ml. Hypaque per pound body weight
in the same two individuals in separate experiments. In these experiments the GFR was normal
and constant so that the results demonstrate the
importance of the plasma Hypaque concentration
in determining the quantity appearing in the urine.
The excretion rate is maximal within a few minutes
of the injection at the time of the peak in the plasma
concentration. Thereafter the excretion rate for
Hypaque closely mirrors the falling plasma concentration. Identical results have been obtained in a
total of 12 experiments in four subjects.
Figure 6 gives the mean cumulative excretion
of Hypaque as a proportion of the injected dose in
15 experiments on normal subjects. At ten minutes
only 12 per cent of the dose has been excreted in the
urine, confirming that the early fall in plasma concentration is only to a small extent due to renal
excretion, but is almost entirely due to dilution by
mixing in the extracellular fluids. At one hour only
38 per cent has been cleared by the kidneys, at three
hours 45 per cent, at six hours 83 per cent and at
24 hours 94-100 per cent.

564

AUGUST 1967

Excretion Urography/
'075ml/lb O-Mml/lb "025ml/lb

50 60 0 10 20 30 40 50 60
TIME-minutes
FIG. 5.
Plasma concentrations and urinary excretion of Hypaque following the intravenous injection of 0-25, 0-50 and 0-75 ml./lb. body weight of Hypaque to the
same two individuals on separate occasions.

l/2

10 20

3
6
HOURS

30 40

12

24

FIG. 6.
Cumulative urinary excretion of Hypaque as a percentage
of the injected dose.

3 4 5 6 7 8 9 10 II
HYPAQUE EXCRETED Qt45mins-q.

12 13

FIG. 7.
Increase in urine flow rate related to the amount of Hypaque
excreted.

565

VOL.

40, No. 476

W. R. Cattell, I. Kelsey Fry, A. G. Spencer and P. Purkiss

to 40, 80 and 120 ml. Hypaque for subjects weighing
The osmotic diuretic action of Hypaque
Figure 7 records the increase in urine flow rate, 160 lb. Similar results were obtained in each indicompared with the control preliminary period, in vidual. Figure 8 records the urine concentrations of
the 45 minutes following the injection of Hypaque Hypaque and the urine flow rate obtained in tenplotted against the amount of Hypaque excreted in minute consecutive collection periods following the
the urine in the same period of time. The analysis is injection in two of these subjects. These results
confined to patients demonstrated to have been ade- clearly demonstrate that the larger doses of Hypaque
quately and comparably dehydrated (preliminary not only produced a greatly increased rate of water
urine flow rates of 0-2-0-5 ml./minute). Following excretion, but also a markedly higher concentration
the injection the rate of water excretion increased of Hypaque in the urine. Once more it is evident
in each patient up to a maximum increment of that the urinary concentration of Hypaque is maxi500 per cent. This diuretic action increased in pro- mal shortly after the injection, and that it steadily
portion to the amount of Hypaque excreted in the declines as the plasma concentration falls.
urine.
To determine whether, despite its diuretic action, State of hydration
The effect of the state of hydration on the urine
higher urine concentrations could be obtained by
larger injections of contrast medium, studies were concentration of Hypaque following the intravenous
completed on five normal subjects under constant injection of 0-75 ml./lb. body weight was assessed
conditions of dehydration. Doses of 0-25, 0-5 and in four normal subjects. These were studied (a)
0-75 ml./lb. body weight were administered, equal in a normal state of hydration, (b) after 14 hours'
0-75ml/lb 050ml/lb

10 20 30 40

0-25ml/lb

50 60 0 10 20 30 40 50 60
TIME-minutes
FIG. 8.
Urinary Hypaque concentration (closed circles) and urine flow rates (histogram)
in consecutive ten-minute urine collections following the injection of Hypaque.

566

AUGUST

1967

Excretion Urography/
'DEHYDRATED

-NON-DEHYDRATED

500- mq/IOOml
400|30051

20012 q/IOOml
10-

2
o
o
3

or
O

86"

f 42800- mq/min
-o

|600|400-

I200H
0

10 20 30 40 50 60 0 10 20 30 40 50 60
TIME - minutes

FIG. 9.
Plasma and urinary Hypaque concentration and Hypaque excretion rate in
consecutive ten-minute samples in two subjects under different conditions of
hydration (see text).

fluid deprivation, (c) after fluid loading (600 ml. of

water per hour for two hours before and during the
experiment), (d) following 14 hours fluid deprivation and the administration of a diuretic (5 mg
bendrofluazide). The results obtained with the two
latter regimes in two subjects are illustrated in
Fig. 9. Although the plasma concentration and the
rate of Hypaque excretion were similar in the same
individual under different conditions of water balance, the urine concentration of Hypaque was markedly increased by previous dehydration, whether
by fluid deprivation or by the diuretic and decreased
by full hydration.
Drip infusion of Hypaque
The rate of urine flow and the urinary Hypaque
concentrations observed in the 45 minutes following single intravenous injection of 80 ml. of Hypaque

in 33 patients were compared with those obtained

following the intravenous infusion of the same
dose in 150 ml. 5 per cent dextrose over ten minutes
in 34 subjects. The two groups were comparable
with respect to initial urine flow rates, mean dose
in ml./lb. body weight, and rates of Hypaque excretion. The results obtained are shown in Figs. 10
and 11. No significant difference was demonstrated
either in urine flow rate of Hypaque concentration.
DISCUSSION

The excretion of urographic contrast media by

the kidneys has been studied previously (Woodruff
and Malvin, 1960; Wigh et al., 1962; Blaufox et al.,
1963; Tauxe et al., 1964; Benness et al, 1965;
Denneberg, 1965), but the lack of a rapid, precise
method of analysis has prevented a detailed correlation between the physiological aspects of their

567

VOL.

40, No. 476

W. R. Cattell, I. Kelsey Fry, A. G. Spencer and P. Purkiss

renal excretion, and the diagnostic quality of the

radiographs. The development of a satisfactory method for estimating 45% Hypaque (sodium diatrizoate)
has now made possible a study of the factors affecting the excretion of this widely used contrast medium. The mode of excretion of other contrast media
may differ according to their chemical composition
(Benness, 1965; Meschan, 1965) and it should be
emphasised that what applies to 45% Hypaque need
not apply to other media.
The excretion of Hypaque has been studied in
animals (Woodruff and Malvin, 1960; Stokes, Conklin and Huntley 1962; Blaufox et al, 1963) and in
man (Tauxe et al, 1964, Denneberg, 1965).
The excretion of any substance in the urine is
the net result of glomerular filtration and the subsequent modification of the filtrate by renal tubular
secretion and reabsorption (Fig. 12). The rate of excretion at the glomerulus is the product of the
glomerular filtration rate (GFR) and the plasma concentration (p) of freely filterable compound (filtered

(34)

l o a d = G F R x p ) . Filterability depends largely on

molecular size and the extent of binding to the
plasma proteins. The small molecular size (Meschan,
1965) permits complete filtration of the free compound. The extent of binding to plasma protein
varies with the physico-chemical conditions and has
been previously reported as 0-10 per cent (Woodruff
and Malvin, 1960; Blaufox et al., 1963; Tauxe et al,
1964; Denneberg, 1965). Uncertainty concerning
the extent of plasma binding largely invalidates the
results of previous studies which have claimed to
demonstrate some degree of tubular secretion
(Denneberg, 1965) and tubular reabsorption (Stokes
et al, 1962; Woodruff and Malvin, 1960). These
points are considered in detail elsewhere (Spencer
et al) For practical purposes in normal subjects
by far the greater part of the excretion of Hypaque
is by glomerular filtration, and there is no important degree of tubular secretion or reabsorption
(Fig. 13). It is thus to be expected that the rate of
excretion of Hypaque in the urine will depend upon

(34)

(33)

(33'

145o
lJ

o
o

a: 4 -

^10-

**

.r

<

8-

B 6"
: 4-

o
o
o

S i-

2-

DRIP
INFUSION

DRIP
NORMAL
INFUSION INJECTION

NORMAL
INJECTION

10.
Urine flow rates obtained following drip infusion compared
with single intravenous injection of 80 ml. of Hypaque.
FIG.

FIG. 11.
Urinary Hypaque concentration obtained following drip
infusion compared with single injection of 80 ml. of Hypaque.

568

AUGUST 1967

Excretion Urography/

FILTRATION FILTERED LOAD =

[PLASMA LEVEL xGF.R.
TUBULAR REABSORPTION
TUBULAR EXCRETION

TUBULAR REABSORPTION

AMOUNT EXCRETED = FILTERED LOAD

+TUBULAR EXCRETION
-TUBULAR REABSORPTION
FIG. 12.
Possible modes of renal excretion.

50 100 150 200 250 300

PLASMA HYPAQUE CONC. mq/IOOml
FIG. 14.
Diagrammatic representation of the relationship between
plasma concentration and urinary excretion of Hypaque
at different rates of glomerular filtration. The stippled band
illustrates that obtain the same excretion rate the plasma
concentration must be increased as GFR is reduced.

> TUBULAR REABSORPTION

(TRIVIAL)
TUBULAR EXCRETION
(DOUBTFUL)

> TUBULAR REABSORPTION

(TRIVIAL)

AMOUNT EXCRETED = FILTERED LOAD

= PLASMA LEVELxG.FR
FIG. 13.
Mode of excretion of Hypaque.

the rate of excretion at the glomerulus, filtered Hypaque passing along the length of the nephron without significant addition or removal (Fig. 13). In the

present studies, the high correlation at all plasma

concentrations between the rate of excretion of Hypaque and the filtered load of Hypaque (Fig. 4)
strongly supports this concept.
The GFR varies with body size, age and sex, and
is greatly affected by the circulatory dynamics and
by intrinsic renal disease. It cannot be artificially
increased to any useful extent in order to improve
urography. By contrast, the plasma concentration
the other factor determining the rate of Hypaque
excretionis readily varied and has been shown to
be dependent initially on dose and body size. Figure 14 not only demonstrates how these two factors are inversely related, but also illustrates how
reduction in GFR can be compensated for by elevation of the plasma level. Together these observations emphasise the need to relate the dose of
Hypaque both to the body size and the GFR of the
patient in order to achieve a predictably high plasma
concentration and maximum rate of excretion of
radio-opaque molecules in the urine. This cannot
be achieved consistently by a fixed dosage schedule

569

VOL.

40, No. 476

W. R. Cattell, I. Kelsey Fry, A. G. Spencer and P. Pur kiss

that takes no account of body size and renal function.

The time/concentration curves for plasma and
urine Hypaque show interesting correlations with
the urographic appearances. The very high concentration of Hypaque in the plasma, glomerular
filtrate and nephron fluid reached in the first five
minutes following the injection coincides with the
early nephrogram which is a feature of high dosage
urography.
The radio-density obtained in the renal outflow
tract depends on the number of Hypaque molecules
in the path of the X rays. This is related to the volume of urine, the concentration of Hypaque in it
and the geometry of the system. The greater the
filling of the pelvi-calycine system and the higher
the concentration of contrast medium the denser the
urogram (Fry et al., 1967). Filling depends on the
rate of water excretion, whereas urine concentration is the net result of the concentration of Hypaque
in the glomerular filtrate (and hence in the plasma)
and the rate of tubular reabsorption of water. The
magnitude of the concentrating effect of the tubular
reabsorption of water may be illustrated as follows:
at a normal GFR of 120 ml./minute and a rate of
urine excretion of 4 ml./minute, since Hypaque is not
significantly reabsorbed or secreted by the renal
tubules, the final urine concentration will be 30
times that in the plasma.
Factors determining the tubular reabsorption of
water are illustrated in Fig. 15. Normally, 90 per
cent of the filtered water is reabsorbed in the proximal tubules as the result of osmotic gradients generated by the active reabsorption of sodium. In the
dehydrated subject, under the influence of antidiuretic hormone, there is a further net reabsorption
of water in the distal part of the nephron. Following an intravenous injection of Hypaque, large numbers of this molecule appear in the glomerular filtrate
and by their osmotic action decrease the net reabsorption of water in the proximal tubules. A greater
residual volume of glomerular filtrate is presented
to the distal segments of the nephron and an osmotic
diuresis results. This is well shown in the present
studies (Fig. 7). In uraemic patients the acute osmotic diuretic action of Hypaque summates with
the pre-existing chronic osmotic diuresis produced
by the high concentration of urea in the blood and
glomerular filtrate.
This diuretic effect of Hypaque, while favouring
complete filling of the collecting system, reduces the
extent to which the original filtrate is concentrated
along the length of the nephron. It has been stated
that the osmotic diuretic action of contrast medium

NORMAL

OSMOTIC DIURESIS

80-90% OF
WATER
REABSORBED

FURTHER O-9/o fOF WATER

REABSORBED
DEPENDANT
ON A.D.H.

REABSORPTION OF
WATER REDUCED

REABSORPTION
REDUCED BUT
SOME OCCURS
IN PRESENCE
OF A.D.H.

FIG. 15.
Factors affecting the reabsorption of water and so urine
concentration under normal conditions and during osmotic
(Hypaque) diuresis.

may so reduce the tubular reabsorption of water that

no increase in the concentration of the medium in
the urine is obtained by giving larger doses above a
certain critical level (Keates, 1953; Harrow, 1955;
Benness, 1965). Keates (1953) found that no increase in the concentration of diodone in the urine
could be demonstrated following the administration
of 40 ml. compared with 20 ml. of 35 per cent diodone. Benness (1965) stated that no increase in concentration was achieved with doses of Urografin
exceeding those which contained 15 g iodine (equivalent to 56 ml. 45% Hypaque) and also reported
that the concentration of contrast medium in the
urine remained constant throughout the period of
study. The present, more detailed studies are not
in accord with such conclusions. On the contrary,
with doses of Hypaque up to 0-75 ml./lb. body
weight, despite the resulting diuresis, there was
always a substantial increase in the concentration of
contrast medium in the urine. The present data
clearly show that the higher dosage of Hypaque
produces both an increase in the concentration and
in the rate of excretion of Hypaque in the urine,
despite the osmotic diuresis. The renal outflow
tract is thereby distended with a greater volume of
urine containing a higher concentration of Hypaque,
and all parts of the urogram are of increased radiodensity (Fry et al., 1967). Ultimately, despite even
higher dosage of Hypaque it may be expected that
no further increase in its urine concentration will be
obtained. This level would be reached at lower dosages in patients with renal disease because of the

570

AUGUST 1967

Excretion Urography/
reduced numbers and impaired functional capacity
of the remaining nephrons.
State of hydration
In view of the marked dose-dependent diuretic
action of Hypaque, it is pertinent to consider the
effect of dehydration on the urinary concentrations
of the contrast medium, particularly when large
doses are employed. The main site of action of osmotic diuretics, such as Hypaque, is in the proximal
parts of the nephron, whereas anti-diuretic hormone
(ADH) has its chief effect on water transfers in the
distal tubules and collecting ducts (Fig. 15). It
would be expected, therefore, that the previous state
of hydration and of ADH secretion would still be
important in affecting the concentration of Hypaque in the urine, despite its osmotic diuretic
action. This is well demonstrated in the experiments
on normal subjects (Fig. 9). In the dehydrated state
the concentration of Hypaque in the urine was 100150 per cent greater than in the hydrated state, at
the same level of dosage.
The proposed introduction of intravenous drip
pyelography (Schencker, 1964; Harris and Harris,
1964) has been followed in some papers by an incorrect concept of the part played by the volume of
fluid infused. This is small, and can play no significant role in determining the subsequent rate of
urine flow. In the present studies of the flow rates
and the concentration of Hypaque in the urine there
was no appreciable difference between those produced by 80 ml. Hypaque given as a single intravenous injection and the same dose administered as
an infusion in 150 ml. 5 per cent dextrose (Figs.
10 and 11). Therefore the high rates of urine flow
obtained by drip pyelography are entirely due to the
large dose of Hypaque and the consequent osmotic
diuresis. The only merit of this technique is for
convenience in giving a big dose of contrast medium.
EXCRETORY UROGRAPHY AS A MEASURE OF RENAL
FUNCTION

large number of independently exercised functions

and these are best assessed by the appropriate specific tests.
ABSTRACT

The development of a simple method for the chemical

analysis of sodium diatrizoate has permitted the investigation of the factors affecting the renal excretion of
45% Hypaque in normal subjects and in patients undergoing routine IVP.
The study has shown that the amount of Hypaque excreted in unit time is a function of the GFR and the plasma
concentration at that time. The rate of excretion is maximal
in the first 1020 minutes following the injection of medium and follows the rise and fall in plasma concentration.
The ten-minute plasma concentration has been shown
to be a function of dose and is readily and accurately reproducible.
Studies of the urinary concentration of Hypaque have
shown that despite prior claims to the contrary, increasing
doses up to 0-75 ml./lb. body weight are associated not only
with increasing urine flow but also increased concentration
of contrast media in the urine. It has been shown that the
concentration of Hypaque in the urine was markedly affected by the state of hydration even with such high dosage.
The interrelation between the plasma and urine concentration of Hypaque, the GFR and the rate of urine flow
in determining the rate of excretion of Hypaque is discussed. A clear understanding of these factors is an essential
basis for the production of high-quality urographic examinations.
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