Furosemide-augmented Results
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LEE
B. TALNER,’
RICHARD
Intravenous
in Essential
A. STONE,2
MARC
Hypertension
N. COEL,3
STEVEN
could
not
urography
screening
sion. In vasodilated
1972, Wolf excretory
sensitive encouraging
phy and presence part of system lengthy
test,
results
to examine in hypertensive
for
not
of
prospectively patients
and
proved
in
clinical
renal
underwent
blood
an extensive
urea
creatinine
nitrogen, clearance.
and angiography
intake
was
supported
in part
not
was
informed
as
range.
controlled
in these
latter
and also The
dietary
patients.
Thus
approved
by
of California,
written
the
Human
Use
San Diego,
Committee
of
and all patients
gave
consent.
of
subjects
a
ml
bolus
of was
Radiographs
Wolf
[2]
Our
reported
purpose
1 .5,
was
vein
for at least of
chemical
creatinine venous
10 days
tests
renin
from
a
renin
afternoon
before
sodium
iothalamate
inejcted
rapidly,
coned and
to the
3 mm
(Conray-400,
diatrizoate usually
kidneys
after
in
after
the
coned
than
taken A full
by a coned-down
Immediately
less
were
injection.
of 50 ml contrast
material.
Mallin-
(Renografin-76%,
length
film
film,
40
30
at 15 sec film
sec.
and was
of the kidneys mg
at
of furosemide
later a film intravenous
The latter was administered
of contrast material in the collecting system at any time. The rapid sequence portion of the examination was scored as abnormal if one or more of the above findings were present.
and
National
either
at 5 mm followed
injection
was not seen
Ureteral notching
and
the
the
to restore the nephrogram to permit accurate tracing of the renal outlines. The rapid sequence portion of the examination was assessed for signs of renovascular disease using the following criteria: (1) difference in renal length (right greater than left by 1.5 cm or more, or left greater than right by 2.0 cm or more); (2) discrepancy of at least 30 sec in the appearance time of contrast material in the calices; and (3) subjective difference in density
activity
October 7, 1977. by grant HL-18095
on
was injected intravenously over 30 sec. Ten minutes coned to the kidneys was taken preceded by a bolus
the As
including
concentration,
a cathartic
sodium-meglumine
2.5,
10 mm.
the renin-angiotensin 45 patients entered vasodilated urography, renal
2,
taken
technique angiogra-
to establish hypertension.
received
urography and had nothing by mouth after midnight. Preliminary films were taken full length and coned to the kidneys. A 50
Measurement Because
day) for 5 days. Furosemide-augmented urography was performed on day 5 at the end of the high salt period, and renal vein renin measurements and angiography were performed at
work
for
was
films;
in the analysis of results. clearances in the normal
hypertension.
investigation
Methods
battery
Received July 26, 1977; accepted
the kidneys
more
of the biochemical tests, angiography, measurements, these 40 patients all had An additional six patients at two other
criteria
the University
was measured after the patient had been on a high salt diet for 5 days, and again after he had been on a low salt diet (20 mEq sodium/
This Service.
or
essential
Squibb)
hospitalized
Peripheral
one
urography
1973
and
and
plasma
on
had vasodilated
or
arteriography,
were
In five patients,
accurately
a total of 46 patients with essential hypertension who underwent vasodilated urography form the basis of this report. All were men, and the average age was 38.0 years ± 10.4 SD. There were 37 white and nine black patients. The entire clinical
Clinical Material
All 45 patients
EMARINE4
the
sodium
hyperten-
the accuracy of the who would be having
Subjects
period.
W.
hospitals
ckrodt)
renal vein renin determinations or absence of renovascular
aortography, determinations.
traced
CHARLES
satisfied
[1] proposed so-called as a more accurate and trials.
a clinical investigation in essential hypertension, protocol which included
to be
renovascular
and Wilson urography
screening
AND
Technique
has
test
be
Based on the results and renal vein renin essential hypertension.
All
sequence
LEVY,2
a result they are not included All patients had creatinine
Introduction
Rapid
B.
the end of the low salt
Giving an Intravenous diuretic during urography (furosemide-augmented urography, vasodilated urography) causes renal swelling which is easily measured. Several investigators have used this observation as the basis of a screening test for renovascular hypertension. They found that normal kidneys enlarge in area by more than 10%, while kidneys with renal artery stenosis show a blunted size response, usually less than 5%. We used the technique in 46 patients with proven essential hypertension in order to further examine its potential usefulness in the hypertensive population. The 92 kidneys showed an average area increase of only 7.0% ± 3.6% SD, and only 15% of the kidneys enlarged by more than 10%. Based on these observations we doubt that vasodilated urography will be valuable as a screening test for renovascular hypertension because of the high incidence of false positive and indeterminate results in patients without renal artery stenosis.
satisfactory
Urography:
on
the
injection
Renal
Institutes
of Renal the renal was
outlines
of Health
films,
used
for
were
and
patients.
Area
outlines
preliminary
in any of these
were the
film
measurement
traced
by the
with
Veterans
often
incompletely visualized 15 sec after contrast of “baseline” renal area.
taken
a thin
waxed
Administration
pencil
Medical
‘Department of Radiology, University Hospital, University of California Medical Center, 225 West Dickinson Street, San Diego, California Division of Nephrology, Veterans Administration Hospital, 3350 La Jolla Village Drive, San Diego, California 92161. 3Department of Radiology, Veterans Administration Hospital, 3350 La Jolla Village Drive, San Diego, California 92161. 4Department of Radiology, Naval Regional Medical Center, San Diego, California 92134.
on the
Research 92103.
2
Am J Ro.ntgenol
© 1978 American
130257-260, February Roentgen Ray Society
1978
257
0361 -803X/78/0200
-0257
$02.00
258
TALNER TABLE Renal
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Area
Area
1
TABLE
Enlargement
increase
Enlargement
23
5.0%-9.9%
5S
>10%
14
film
and
using
baseline increase
on the
a compensating
polar
centimeters.
All tracings
or checked
0%-5% 0%-5%, 10% Both5%-10% One 5%-lO%, 15% Both>10%
measured was 7.0%
postfurosemide
10 mm after 3.6% SD.
film,
and
were
planimeter
and
was
expressed
and measurements
by one of us (L. B. Tamer
patients
on
the
had a positive
basis
of
sec
film
to
the
10
mm
for
sequence
delayed
urogram,
appearance,
postfurosemide
and
the
initial
film
in
92
kidneys. The average area increase for each kidney was 7.0% ± 3.6% SD. Twenty-three kidneys (25%) increased between 0% and 4.9%, 55 kidneys (60%) increased between 5.0% and 9.9%, and 14 kidneys (15%) increased more than 10% in area. Table 2 groups the same data according to whether the two kidneys of each patient enlarged 0%-5%, 5%-10%, or by more than 10%. For the entire group the average difference in enlargement of the paired kidneys of each patient was 2.6% ± 1 .8 (range, 0.4%-7.8%). The data were tested to see whether the degree of renal enlargement correlated with patient age, mean blood pressure, or supine peripheral venous renin activity in the sodium-depleted state. The correlation coeff icients were .30, .09, and .10, respectively; none was statistically significant (P > .10). -
Discussion
In 1972, the National Cooperative Study on Hypertension [3] evaluated the results of rapid sequence urography as a screening test for renovascular hypertension. In patients with unilateral renal artery stenosis who were cured or improved by surgery, the rapid sequence urogram was positive in 83%. The 17% false negative studies attested to the inadequacy of rapid sequence urography as a screening test. In other studies, radionuclide renography [4] and the saralasin infusion test [5, 6] have similarly tests.
proved
be
less
than
investigators
activity, [7]
or
either related
to
foolproof
have
proposed
measured
under
urinary
9 20 one
3.8±2.0 2.0± 1.5
10%6 4
3.3±1.6 4.0±2.1
46
cannot
taken
10 mm
2.6
after
1.8*
±
furosemide
mnjec-
sodium
that
controlled excretion
peripheral
condi[8],
is a
screening test for renovascular hypertension. a high peripheral renin activity is found in many with renovascular hypertension, this is not unithe case [9, 10]. Peripheral renin activity measure-
an ideal
hypertension. rapid sequence
screening
urography
is not
test
an ideal
screening examination for renovascular hypertension, urography continues to be performed in many hypertensive patients younger than 50 years of age, and in patients over 50 with severe or difficult to manage hypertension. While a major indication for urography in these patients is to screen for nonvascular renal disease (e.g., atrophic kidney, hydronephrosis, cyst, tumor, polycycstic
disease)
hypertension,
which
it would
modification
of
into
acceptable
a truly
context, urography
the
The
rationale
kidneys
encouraging were most
for
in renal to result
size. from
that
the
2,
the
enlarge
13];
but
diuretic, minutes
furosemide,
and
tubular
likely
a
consistent
loop
increase
increase in renal blood flow caused
volume
cause
size by
urography
Nevertheless,
renal
artery
already stenosis.
furosemide substantially
enlargement.
excretory
to furosemide,
were the
accompanying
for renal
vasodilated
with
in response for
Normal
of a diuretic.
an osmotic within several
appropriate.
kidneys
such kidneys compensate
vasodilated
is as follows.
marked
term
be entirely that
12,
increased
Consequently, served
with
it
In this
the term vasodilated excretory urogrecent animal experiments [14] sug-
is a more
not
transform
to the injection
Wolf considered the an increase in renal
the diuresis may
could
technique
a more
for
if a simple
procedure.
material, enlargement
the diuretic; hence, raphy [1]. However, gest
urography
the
[1,
causes
responsible
gratifying
screening
in response
inejction
diuretic,
be
most
results of Wolf welcome [2, 11].
Urographic contrast causes modest renal after
might
be
standard
enlarge
urography
as screening
yet be considered
renovascular Even though
increase
Several
renin tions reliable While patients formly
to
5%-
Total
in
.8
±
were done
one on the basis of a 2.0 cm length differential. Table 1 summarizes the area changes from 15
one
1 .4
or C. W. Emarine).
rapid
a 1 mm
Average Difference between Two Kidneys
No. Patients
Note-Measurements tion. Range, O.4%-7.8%.
ments Three
Kidneys
(%)
Results two
by Paired
7
Both One
transferred to tracing paper. A medial tangent line was drawn between the upper and lower poles. Renal area was measured square
Grouped
Area Increase
92
- Percentage increase over furosemide injection. Average
15 sec
2
No. Kidneys
0%-4.9%
Total
initial
ET AL.
stenosis
presumably
maximally It followed
injection in size,
caused no
stenosis
Wolf
ob-
failed
to
because
vasodilated to that if during
the
kidney
was
to
present.
Conversely, if a kidney failed to enlarge, stenosis very likely was present. It was found that measurements of renal area changes were more reliable than measurements of renal length changes; and that an area increase greater than 10% was definitely normal, while an area increase indicated
of
less
a high
than
5%
likelihood
was of
definitely
abnormal
stenosis
[1].
Here
and then
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FUROSEM1DE-AUGMENTED
INTRAVENOUS
was an absolute measurement which could potentially detect bilateral stenosis, a long recognized deficiency of standard rapid sequence urography. In our 46 patients with angiographically proved essential hypertension, the incidence of false positive vasodilated urography, using the above criteria, was 25%. That is, 23 of 92 kidneys had less than 5% increase in renal area after furosemide. The area increased 5%-9.9% in 60% of the kidneys. According to Wolf, this is a “gray” area of limited clinical value [1]. Only 15% had a greater than 10% area increase, the definite “normal” response. While we have not used the technique in many patients with renovascular hypertension, the widely varying resuIts in our patients with essential hypertension suggest that vasodilated urography will not be a useful screening test for renovascular hypertension because of the large number of false positive and indeterminate studies. In our patients, no correlation was demonstrated between the degree of renal enlargement and age, race, blood pressure, or peripheral renin activity. The average renal enlargement following contrast material and furosemide was 7%. This is considerably less than that found by Wolf [1] and Dorph and Oigaard [15] in related studies on patients with essential hypertension. There are 5everal factors which might explain at least part of the discrepant results. As originally described [1], the essential elements of the technique were: (1) 50 ml bolus injection of sodium iothalamate over 20-30 sec; (2) films at 30 sec, 1 2, 3, 5, 8, and 15 mm; (3) 50 mg ethacrynic acid injected intravenously 3-5 mm after the contrast material; (4) infusion of contrast material plus saline to maintain the nephrogram; and (5) tracing of renal outlines and comparison of 15 mm film with preinjection film. Performed this way, vasodilated urography yielded an average renal enlargement of 16% in patients with essential hypertension. However, since this type of study precluded a reliable anatomic study of the kidneys, Wolf recommended that the protocol be modified as follows: (1) inject bolus of contrast material as usual; (2) obtain films over a 10 mm period to yield a standard anatomic examination of the urinary tract; (3) inject ethacrynic acid or furosemide intravenously; (4) infuse dilute contrast material; and (5) take coned film of kidneys 10 mm after injection of the diuretic. ,
Diuretic
Agent
Dorph ics:
and
mannitol,
[15] examined furosemide,
urea,
a variety of diuretand ethacrynic acid.
All were found to cause a maximum ll% increase in renal area during clinical urography. Moreover, giving ethacrynic acid just after a bolus of contrast material caused no greater enlargement than giving it 10 mm after contrast material injection. Hence, the fact that we used
explain
furosemide
rather
our smaller
than
observed
ethacrynic
area
acid
should
not
increase.
Film
for
Wolf on
Salt
The large majority of our patients were on salt intake for the 5 days prior to the examination.
a liberal Based
Measurements
[1] found
92%
that
of the
cathartics
the kidney
preliminary
the
see the preliminary
outlines
x-rays
could
(baseline
15
day
sec
after
15 sec
before,
we
generally
major portion of the films. Consequently,
patients. be seen
be traced
area).
In the
contrast
were
unable
to
renal shadows on the we used the film taken
injection
as
our
baseline
in
all
In several patients in whom the kidneys could clearly on the preliminary films as well as on the postcontrast
film,
there
was
either
no
difference
in area or a slight (l%) decrease in area on the 15 sec film. This agrees with our animal studies [14], and the clinical studies of Dorph and Oigaard [12]. We did not use a correction factor for the 15 sec “baseline” area and do not believe this is in any way responsible for the discrepant results. Time
of Postdiuretic
After ment
injection occurs
Film of
a diuretic,
between
postfurosemide demonstrate
maximum
10 and
15 mm
renal
enlarge-
[1, 12]. Our
10 mm
film should have been appropriate the maximum renal size change.
Maintaining
the
Nephro
collecting
system
and
nephrogram.
While
still
accurately
be traced
of a diuretic of the contrast an
accelerated
in some on
patients the
10 mm
during material fading
the
is
given
in
postdiuretic contrast maximally
material dense
of the
a bolus
dilute uretic results
an
film.
attempt
to
of the
may
postdiuretic
guarantee
urin
kidneys
film,
in many others they will be too faint or partially by bowel gas. For this reason, additional contrast rial
to
gram
Intravenous administration ography causes rapid dilution
tracing
Intake
Baseline
remaining patients the film taken 30 sec or 1 mm after contrast material injection was used for the “baseline” tracings, assuming a 2% or a 5% area increase, respecitvely, to result from the contrast material itself. In our patients, in spite of attempted bowel cleansing with
ing Preurography
259
on experimental studies showing that preloading with salt maximizes the increase in renal blood flow [16] as well as the diuresis following furosemide injection [17], we would have predicted that our patients would demonstrate a maximum renal enlargement. In another 79 patients with presumed essential hypertension (normal rapid sequence urogram, but no angiographic confirmation), we performed the study without controlling the dietary sodium or stopping medications. The average enlargement of these 158 kidneys was 6.6% ± 4.4% SD (L. B. Talner, unpublished data). Since this is no different from the response in the sodium-repleted patients, we conclude that the liberal sodium intake itself does not account for the unexpectedly small renal enlargement in our study group.
the
Oigaard
UROGRAPHY
hidden mate-
a successful
We
chose to inject a 50 ml bolus 15 sec before the late film to achieve nephrogram
renal
of contrast
outlines. material,
and
Wolf
thereby [1],
rather
recommended
of a
facilitate than
the inject-
infusing
contrast material during the period between injection and the late film. When we analyzed and found the relatively small renal enlargement,
diour
TALNER
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260
we considered the possibility that this departure in technique (i.e., bolus rather than infusion) accounted for at least part of the difference in results. Such a consideration was based on the knowledge that a slow infusion of contrast material contributes to renal enlargement while a bolus injection causes a temporary mild shrinkage [14]. To test this possiblity, we recently studied 19 patients with an average age of 38.6 years ± 17.4 SD who were presumed to have essential hypertension based on clinical, laboratory, and urographic findings and/or angiographic findings (nine patients). Vasodilated urography was performed with either meglumine-sodium iothalamate (Vascoray, Mallinckrodt) or sodium-meglumine diatrizoate (Renografin-76%) as described in the methods section, with the sole exception that 50 ml of contrast material
mm
was
infused
postfurosemide
swelling Eleven (45%)
averaged kidneys increased
increased
the
5 mm
preceding
film.
With
this
technique,
5.2%
SD
7.6%
±
(29%) increased 5%-9.9%, and
in area
ence, we do as a screening
during
by
10%
or more.
not believe vasodilated test in renovascular
in the
the
kidneys
Based
on this
urography hypertension.
Theda Hermes for excellent secretarial Rosen for help in analyzing the data.
5.
6. 7. 8.
9.
(26%)
10.
11 .
experiis useful 12.
ACKNOWLEDGMENTS
We thank
4.
10
renal 38 kidneys. 17 kidneys
0%-4.9%, only 10
ET AL.
assistance
and Dr. Lowell
REFERENCES 1. Wolf GL, Wilson WJ: Vasodilated excretory urography: improved screening test for renal arterial stenosis? Am J Roentgenol 114:684-689, 1972 2. Wolf GL: Rationale and use of vasodilated excretory urography in screening for renovascular hypertension. Am J Roentgenol 119:692-700, 1973 3. Bookstein JJ, Abrams HL, Buenger RE, Lecky J, Franklin SS, Reiss MD, Bleifer KH, Klatte EC, Varady PD, Maxwell MH: Radiologic aspects of renovascular hypertension. II.
The role of urography in unilateral renovascular disease. JAMA 220:1225-1230, 1972 Maxwell MH, Lupu AN, Taplin GV: Radioisotope renogram in renal arterial hypertension.J Urol 100:376-383, 1968 Thomas AD, Ball SG, Lee MA: Failure of saralasin to predict a response to surgery in renovascualr hypertension. Lancet 1 :724-726, 1977 Streeten DHP, Anderson GH Jr: Angiotensin blockade in hypertension (editorial). Ann Intern Med 86:353-354, 1977 Wallach L, Nyarai I, Dawson K: Stimualted renin: a screening test for hypertension. Ann Intern Med 82 :27-34, 1975 Laragh JH, Sealey JE, BUhler FR, Vaughan Ed, Brunner HA, Gavras H, Baer L: The renin axis and vasoconstriction volume analysis for understanding and treating renovascularand renal hypertension.AmJMed 58:4-12, 1975 Marks LS, Maxwell MH: Renal vein renin. Value and limitations in the prediction of operative results. Urol Clin North Am 2:311-325, 1975 Marks
LS,
Maxwell
MH,
Kaufman
JJ:
Non-renin
mediated
renovascular hypertension : a new syndrome? Lancet 1 : 615617, 1977 Wolf GL, Wilson WJ: Vasodilator reserve, parallel vascular beds, and significant stenosis: a review for the angiographer. CRC Crit Rev Clin Radiol NucI Med 5 : 1-74, 1974 Dorph 5, Oigaard A: Variations in size of the normal kidney
following intravenous administration of water-soluble contrast medium and urea. BrJRadiol46:183-186, 1973 13. Wolpert SM: Variation in kidney length during the intravenous pyelogram. Br J Radiol 38:100-103, 1965 14.
Dorph
5, Sovak
size change 250, 1977
M, Talner
during
IV.
LB,
Rosen
urography?
L: Why does kidney Invest Radiol 12:246-
15. Dorph 5, Oigaard A:Renal distension in response to watersoluble contrast medium and various diuretics. Scand J UrolNephrol 9:114-118,1975 16. Levy SB, Lilley JJ, Frigon RP, Stone RA: Urinary kallikrein and plasma renin activity as determinants of renal blood flow: the influence of race and dietary sodium intake. J Clin Invest 60:129-138, 1977 17. DirksJH, SeelyJF: Effect of saline infusions and furosemide on the dog distal nephron.AmJPhysiol 219:114-121,1970
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LEE
B. TALNER,’
RICHARD
Intravenous
in Essential
A. STONE,2
MARC
Hypertension
N. COEL,3
STEVEN
could
not
urography
screening
sion. In vasodilated
1972, Wolf excretory
sensitive encouraging
phy and presence part of system lengthy
test,
results
to examine in hypertensive
for
not
of
prospectively patients
and
proved
in
clinical
renal
underwent
blood
an extensive
urea
creatinine
nitrogen, clearance.
and angiography
intake
was
supported
in part
not
was
informed
as
range.
controlled
in these
latter
and also The
dietary
patients.
Thus
approved
by
of California,
written
the
Human
Use
San Diego,
Committee
of
and all patients
gave
consent.
of
subjects
a
ml
bolus
of was
Radiographs
Wolf
[2]
Our
reported
purpose
1 .5,
was
vein
for at least of
chemical
creatinine venous
10 days
tests
renin
from
a
renin
afternoon
before
sodium
iothalamate
inejcted
rapidly,
coned and
to the
3 mm
(Conray-400,
diatrizoate usually
kidneys
after
in
after
the
coned
than
taken A full
by a coned-down
Immediately
less
were
injection.
of 50 ml contrast
material.
Mallin-
(Renografin-76%,
length
film
film,
40
30
at 15 sec film
sec.
and was
of the kidneys mg
at
of furosemide
later a film intravenous
The latter was administered
of contrast material in the collecting system at any time. The rapid sequence portion of the examination was scored as abnormal if one or more of the above findings were present.
and
National
either
at 5 mm followed
injection
was not seen
Ureteral notching
and
the
the
to restore the nephrogram to permit accurate tracing of the renal outlines. The rapid sequence portion of the examination was assessed for signs of renovascular disease using the following criteria: (1) difference in renal length (right greater than left by 1.5 cm or more, or left greater than right by 2.0 cm or more); (2) discrepancy of at least 30 sec in the appearance time of contrast material in the calices; and (3) subjective difference in density
activity
October 7, 1977. by grant HL-18095
on
was injected intravenously over 30 sec. Ten minutes coned to the kidneys was taken preceded by a bolus
the As
including
concentration,
a cathartic
sodium-meglumine
2.5,
10 mm.
the renin-angiotensin 45 patients entered vasodilated urography, renal
2,
taken
technique angiogra-
to establish hypertension.
received
urography and had nothing by mouth after midnight. Preliminary films were taken full length and coned to the kidneys. A 50
Measurement Because
day) for 5 days. Furosemide-augmented urography was performed on day 5 at the end of the high salt period, and renal vein renin measurements and angiography were performed at
work
for
was
films;
in the analysis of results. clearances in the normal
hypertension.
investigation
Methods
battery
Received July 26, 1977; accepted
the kidneys
more
of the biochemical tests, angiography, measurements, these 40 patients all had An additional six patients at two other
criteria
the University
was measured after the patient had been on a high salt diet for 5 days, and again after he had been on a low salt diet (20 mEq sodium/
This Service.
or
essential
Squibb)
hospitalized
Peripheral
one
urography
1973
and
and
plasma
on
had vasodilated
or
arteriography,
were
In five patients,
accurately
a total of 46 patients with essential hypertension who underwent vasodilated urography form the basis of this report. All were men, and the average age was 38.0 years ± 10.4 SD. There were 37 white and nine black patients. The entire clinical
Clinical Material
All 45 patients
EMARINE4
the
sodium
hyperten-
the accuracy of the who would be having
Subjects
period.
W.
hospitals
ckrodt)
renal vein renin determinations or absence of renovascular
aortography, determinations.
traced
CHARLES
satisfied
[1] proposed so-called as a more accurate and trials.
a clinical investigation in essential hypertension, protocol which included
to be
renovascular
and Wilson urography
screening
AND
Technique
has
test
be
Based on the results and renal vein renin essential hypertension.
All
sequence
LEVY,2
a result they are not included All patients had creatinine
Introduction
Rapid
B.
the end of the low salt
Giving an Intravenous diuretic during urography (furosemide-augmented urography, vasodilated urography) causes renal swelling which is easily measured. Several investigators have used this observation as the basis of a screening test for renovascular hypertension. They found that normal kidneys enlarge in area by more than 10%, while kidneys with renal artery stenosis show a blunted size response, usually less than 5%. We used the technique in 46 patients with proven essential hypertension in order to further examine its potential usefulness in the hypertensive population. The 92 kidneys showed an average area increase of only 7.0% ± 3.6% SD, and only 15% of the kidneys enlarged by more than 10%. Based on these observations we doubt that vasodilated urography will be valuable as a screening test for renovascular hypertension because of the high incidence of false positive and indeterminate results in patients without renal artery stenosis.
satisfactory
Urography:
on
the
injection
Renal
Institutes
of Renal the renal was
outlines
of Health
films,
used
for
were
and
patients.
Area
outlines
preliminary
in any of these
were the
film
measurement
traced
by the
with
Veterans
often
incompletely visualized 15 sec after contrast of “baseline” renal area.
taken
a thin
waxed
Administration
pencil
Medical
‘Department of Radiology, University Hospital, University of California Medical Center, 225 West Dickinson Street, San Diego, California Division of Nephrology, Veterans Administration Hospital, 3350 La Jolla Village Drive, San Diego, California 92161. 3Department of Radiology, Veterans Administration Hospital, 3350 La Jolla Village Drive, San Diego, California 92161. 4Department of Radiology, Naval Regional Medical Center, San Diego, California 92134.
on the
Research 92103.
2
Am J Ro.ntgenol
© 1978 American
130257-260, February Roentgen Ray Society
1978
257
0361 -803X/78/0200
-0257
$02.00
258
TALNER TABLE Renal
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Area
Area
1
TABLE
Enlargement
increase
Enlargement
23
5.0%-9.9%
5S
>10%
14
film
and
using
baseline increase
on the
a compensating
polar
centimeters.
All tracings
or checked
0%-5% 0%-5%, 10% Both5%-10% One 5%-lO%, 15% Both>10%
measured was 7.0%
postfurosemide
10 mm after 3.6% SD.
film,
and
were
planimeter
and
was
expressed
and measurements
by one of us (L. B. Tamer
patients
on
the
had a positive
basis
of
sec
film
to
the
10
mm
for
sequence
delayed
urogram,
appearance,
postfurosemide
and
the
initial
film
in
92
kidneys. The average area increase for each kidney was 7.0% ± 3.6% SD. Twenty-three kidneys (25%) increased between 0% and 4.9%, 55 kidneys (60%) increased between 5.0% and 9.9%, and 14 kidneys (15%) increased more than 10% in area. Table 2 groups the same data according to whether the two kidneys of each patient enlarged 0%-5%, 5%-10%, or by more than 10%. For the entire group the average difference in enlargement of the paired kidneys of each patient was 2.6% ± 1 .8 (range, 0.4%-7.8%). The data were tested to see whether the degree of renal enlargement correlated with patient age, mean blood pressure, or supine peripheral venous renin activity in the sodium-depleted state. The correlation coeff icients were .30, .09, and .10, respectively; none was statistically significant (P > .10). -
Discussion
In 1972, the National Cooperative Study on Hypertension [3] evaluated the results of rapid sequence urography as a screening test for renovascular hypertension. In patients with unilateral renal artery stenosis who were cured or improved by surgery, the rapid sequence urogram was positive in 83%. The 17% false negative studies attested to the inadequacy of rapid sequence urography as a screening test. In other studies, radionuclide renography [4] and the saralasin infusion test [5, 6] have similarly tests.
proved
be
less
than
investigators
activity, [7]
or
either related
to
foolproof
have
proposed
measured
under
urinary
9 20 one
3.8±2.0 2.0± 1.5
10%6 4
3.3±1.6 4.0±2.1
46
cannot
taken
10 mm
2.6
after
1.8*
±
furosemide
mnjec-
sodium
that
controlled excretion
peripheral
condi[8],
is a
screening test for renovascular hypertension. a high peripheral renin activity is found in many with renovascular hypertension, this is not unithe case [9, 10]. Peripheral renin activity measure-
an ideal
hypertension. rapid sequence
screening
urography
is not
test
an ideal
screening examination for renovascular hypertension, urography continues to be performed in many hypertensive patients younger than 50 years of age, and in patients over 50 with severe or difficult to manage hypertension. While a major indication for urography in these patients is to screen for nonvascular renal disease (e.g., atrophic kidney, hydronephrosis, cyst, tumor, polycycstic
disease)
hypertension,
which
it would
modification
of
into
acceptable
a truly
context, urography
the
The
rationale
kidneys
encouraging were most
for
in renal to result
size. from
that
the
2,
the
enlarge
13];
but
diuretic, minutes
furosemide,
and
tubular
likely
a
consistent
loop
increase
increase in renal blood flow caused
volume
cause
size by
urography
Nevertheless,
renal
artery
already stenosis.
furosemide substantially
enlargement.
excretory
to furosemide,
were the
accompanying
for renal
vasodilated
with
in response for
Normal
of a diuretic.
an osmotic within several
appropriate.
kidneys
such kidneys compensate
vasodilated
is as follows.
marked
term
be entirely that
12,
increased
Consequently, served
with
it
In this
the term vasodilated excretory urogrecent animal experiments [14] sug-
is a more
not
transform
to the injection
Wolf considered the an increase in renal
the diuresis may
could
technique
a more
for
if a simple
procedure.
material, enlargement
the diuretic; hence, raphy [1]. However, gest
urography
the
[1,
causes
responsible
gratifying
screening
in response
inejction
diuretic,
be
most
results of Wolf welcome [2, 11].
Urographic contrast causes modest renal after
might
be
standard
enlarge
urography
as screening
yet be considered
renovascular Even though
increase
Several
renin tions reliable While patients formly
to
5%-
Total
in
.8
±
were done
one on the basis of a 2.0 cm length differential. Table 1 summarizes the area changes from 15
one
1 .4
or C. W. Emarine).
rapid
a 1 mm
Average Difference between Two Kidneys
No. Patients
Note-Measurements tion. Range, O.4%-7.8%.
ments Three
Kidneys
(%)
Results two
by Paired
7
Both One
transferred to tracing paper. A medial tangent line was drawn between the upper and lower poles. Renal area was measured square
Grouped
Area Increase
92
- Percentage increase over furosemide injection. Average
15 sec
2
No. Kidneys
0%-4.9%
Total
initial
ET AL.
stenosis
presumably
maximally It followed
injection in size,
caused no
stenosis
Wolf
ob-
failed
to
because
vasodilated to that if during
the
kidney
was
to
present.
Conversely, if a kidney failed to enlarge, stenosis very likely was present. It was found that measurements of renal area changes were more reliable than measurements of renal length changes; and that an area increase greater than 10% was definitely normal, while an area increase indicated
of
less
a high
than
5%
likelihood
was of
definitely
abnormal
stenosis
[1].
Here
and then
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FUROSEM1DE-AUGMENTED
INTRAVENOUS
was an absolute measurement which could potentially detect bilateral stenosis, a long recognized deficiency of standard rapid sequence urography. In our 46 patients with angiographically proved essential hypertension, the incidence of false positive vasodilated urography, using the above criteria, was 25%. That is, 23 of 92 kidneys had less than 5% increase in renal area after furosemide. The area increased 5%-9.9% in 60% of the kidneys. According to Wolf, this is a “gray” area of limited clinical value [1]. Only 15% had a greater than 10% area increase, the definite “normal” response. While we have not used the technique in many patients with renovascular hypertension, the widely varying resuIts in our patients with essential hypertension suggest that vasodilated urography will not be a useful screening test for renovascular hypertension because of the large number of false positive and indeterminate studies. In our patients, no correlation was demonstrated between the degree of renal enlargement and age, race, blood pressure, or peripheral renin activity. The average renal enlargement following contrast material and furosemide was 7%. This is considerably less than that found by Wolf [1] and Dorph and Oigaard [15] in related studies on patients with essential hypertension. There are 5everal factors which might explain at least part of the discrepant results. As originally described [1], the essential elements of the technique were: (1) 50 ml bolus injection of sodium iothalamate over 20-30 sec; (2) films at 30 sec, 1 2, 3, 5, 8, and 15 mm; (3) 50 mg ethacrynic acid injected intravenously 3-5 mm after the contrast material; (4) infusion of contrast material plus saline to maintain the nephrogram; and (5) tracing of renal outlines and comparison of 15 mm film with preinjection film. Performed this way, vasodilated urography yielded an average renal enlargement of 16% in patients with essential hypertension. However, since this type of study precluded a reliable anatomic study of the kidneys, Wolf recommended that the protocol be modified as follows: (1) inject bolus of contrast material as usual; (2) obtain films over a 10 mm period to yield a standard anatomic examination of the urinary tract; (3) inject ethacrynic acid or furosemide intravenously; (4) infuse dilute contrast material; and (5) take coned film of kidneys 10 mm after injection of the diuretic. ,
Diuretic
Agent
Dorph ics:
and
mannitol,
[15] examined furosemide,
urea,
a variety of diuretand ethacrynic acid.
All were found to cause a maximum ll% increase in renal area during clinical urography. Moreover, giving ethacrynic acid just after a bolus of contrast material caused no greater enlargement than giving it 10 mm after contrast material injection. Hence, the fact that we used
explain
furosemide
rather
our smaller
than
observed
ethacrynic
area
acid
should
not
increase.
Film
for
Wolf on
Salt
The large majority of our patients were on salt intake for the 5 days prior to the examination.
a liberal Based
Measurements
[1] found
92%
that
of the
cathartics
the kidney
preliminary
the
see the preliminary
outlines
x-rays
could
(baseline
15
day
sec
after
15 sec
before,
we
generally
major portion of the films. Consequently,
patients. be seen
be traced
area).
In the
contrast
were
unable
to
renal shadows on the we used the film taken
injection
as
our
baseline
in
all
In several patients in whom the kidneys could clearly on the preliminary films as well as on the postcontrast
film,
there
was
either
no
difference
in area or a slight (l%) decrease in area on the 15 sec film. This agrees with our animal studies [14], and the clinical studies of Dorph and Oigaard [12]. We did not use a correction factor for the 15 sec “baseline” area and do not believe this is in any way responsible for the discrepant results. Time
of Postdiuretic
After ment
injection occurs
Film of
a diuretic,
between
postfurosemide demonstrate
maximum
10 and
15 mm
renal
enlarge-
[1, 12]. Our
10 mm
film should have been appropriate the maximum renal size change.
Maintaining
the
Nephro
collecting
system
and
nephrogram.
While
still
accurately
be traced
of a diuretic of the contrast an
accelerated
in some on
patients the
10 mm
during material fading
the
is
given
in
postdiuretic contrast maximally
material dense
of the
a bolus
dilute uretic results
an
film.
attempt
to
of the
may
postdiuretic
guarantee
urin
kidneys
film,
in many others they will be too faint or partially by bowel gas. For this reason, additional contrast rial
to
gram
Intravenous administration ography causes rapid dilution
tracing
Intake
Baseline
remaining patients the film taken 30 sec or 1 mm after contrast material injection was used for the “baseline” tracings, assuming a 2% or a 5% area increase, respecitvely, to result from the contrast material itself. In our patients, in spite of attempted bowel cleansing with
ing Preurography
259
on experimental studies showing that preloading with salt maximizes the increase in renal blood flow [16] as well as the diuresis following furosemide injection [17], we would have predicted that our patients would demonstrate a maximum renal enlargement. In another 79 patients with presumed essential hypertension (normal rapid sequence urogram, but no angiographic confirmation), we performed the study without controlling the dietary sodium or stopping medications. The average enlargement of these 158 kidneys was 6.6% ± 4.4% SD (L. B. Talner, unpublished data). Since this is no different from the response in the sodium-repleted patients, we conclude that the liberal sodium intake itself does not account for the unexpectedly small renal enlargement in our study group.
the
Oigaard
UROGRAPHY
hidden mate-
a successful
We
chose to inject a 50 ml bolus 15 sec before the late film to achieve nephrogram
renal
of contrast
outlines. material,
and
Wolf
thereby [1],
rather
recommended
of a
facilitate than
the inject-
infusing
contrast material during the period between injection and the late film. When we analyzed and found the relatively small renal enlargement,
diour
TALNER
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260
we considered the possibility that this departure in technique (i.e., bolus rather than infusion) accounted for at least part of the difference in results. Such a consideration was based on the knowledge that a slow infusion of contrast material contributes to renal enlargement while a bolus injection causes a temporary mild shrinkage [14]. To test this possiblity, we recently studied 19 patients with an average age of 38.6 years ± 17.4 SD who were presumed to have essential hypertension based on clinical, laboratory, and urographic findings and/or angiographic findings (nine patients). Vasodilated urography was performed with either meglumine-sodium iothalamate (Vascoray, Mallinckrodt) or sodium-meglumine diatrizoate (Renografin-76%) as described in the methods section, with the sole exception that 50 ml of contrast material
mm
was
infused
postfurosemide
swelling Eleven (45%)
averaged kidneys increased
increased
the
5 mm
preceding
film.
With
this
technique,
5.2%
SD
7.6%
±
(29%) increased 5%-9.9%, and
in area
ence, we do as a screening
during
by
10%
or more.
not believe vasodilated test in renovascular
in the
the
kidneys
Based
on this
urography hypertension.
Theda Hermes for excellent secretarial Rosen for help in analyzing the data.
5.
6. 7. 8.
9.
(26%)
10.
11 .
experiis useful 12.
ACKNOWLEDGMENTS
We thank
4.
10
renal 38 kidneys. 17 kidneys
0%-4.9%, only 10
ET AL.
assistance
and Dr. Lowell
REFERENCES 1. Wolf GL, Wilson WJ: Vasodilated excretory urography: improved screening test for renal arterial stenosis? Am J Roentgenol 114:684-689, 1972 2. Wolf GL: Rationale and use of vasodilated excretory urography in screening for renovascular hypertension. Am J Roentgenol 119:692-700, 1973 3. Bookstein JJ, Abrams HL, Buenger RE, Lecky J, Franklin SS, Reiss MD, Bleifer KH, Klatte EC, Varady PD, Maxwell MH: Radiologic aspects of renovascular hypertension. II.
The role of urography in unilateral renovascular disease. JAMA 220:1225-1230, 1972 Maxwell MH, Lupu AN, Taplin GV: Radioisotope renogram in renal arterial hypertension.J Urol 100:376-383, 1968 Thomas AD, Ball SG, Lee MA: Failure of saralasin to predict a response to surgery in renovascualr hypertension. Lancet 1 :724-726, 1977 Streeten DHP, Anderson GH Jr: Angiotensin blockade in hypertension (editorial). Ann Intern Med 86:353-354, 1977 Wallach L, Nyarai I, Dawson K: Stimualted renin: a screening test for hypertension. Ann Intern Med 82 :27-34, 1975 Laragh JH, Sealey JE, BUhler FR, Vaughan Ed, Brunner HA, Gavras H, Baer L: The renin axis and vasoconstriction volume analysis for understanding and treating renovascularand renal hypertension.AmJMed 58:4-12, 1975 Marks LS, Maxwell MH: Renal vein renin. Value and limitations in the prediction of operative results. Urol Clin North Am 2:311-325, 1975 Marks
LS,
Maxwell
MH,
Kaufman
JJ:
Non-renin
mediated
renovascular hypertension : a new syndrome? Lancet 1 : 615617, 1977 Wolf GL, Wilson WJ: Vasodilator reserve, parallel vascular beds, and significant stenosis: a review for the angiographer. CRC Crit Rev Clin Radiol NucI Med 5 : 1-74, 1974 Dorph 5, Oigaard A: Variations in size of the normal kidney
following intravenous administration of water-soluble contrast medium and urea. BrJRadiol46:183-186, 1973 13. Wolpert SM: Variation in kidney length during the intravenous pyelogram. Br J Radiol 38:100-103, 1965 14.
Dorph
5, Sovak
size change 250, 1977
M, Talner
during
IV.
LB,
Rosen
urography?
L: Why does kidney Invest Radiol 12:246-
15. Dorph 5, Oigaard A:Renal distension in response to watersoluble contrast medium and various diuretics. Scand J UrolNephrol 9:114-118,1975 16. Levy SB, Lilley JJ, Frigon RP, Stone RA: Urinary kallikrein and plasma renin activity as determinants of renal blood flow: the influence of race and dietary sodium intake. J Clin Invest 60:129-138, 1977 17. DirksJH, SeelyJF: Effect of saline infusions and furosemide on the dog distal nephron.AmJPhysiol 219:114-121,1970
