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Proceduresof Choice in Renal Nuclear Medicine


M. Donald Blaufox

Department ofNuclear Medicine, Albert Einstein College ofMedicine/Montefiore Medical Center, Bronx, New York

radionuclide method for measuring residual urine, which


The uronephrologicapplicationsof nuclear medicine have was described more than 20 years ago, has not achieved
reached a stage of maturity where procedures of choice for general use and may now be largely obsolete. Testicular
many specificclinicalproblemscan be identified.This review imaging is established in genitourinary imaging while the
attempts to achieve this aim as objectively as possible. It application of radionuclides to studies of patients with
must be emphasizedthat the opinionsexpressedhere are impotence and related diseases is rapidly moving toward
those of the author and in many areas there may be a lack of clinical practice and will likely expand this area of use in
consensus. the future.
J NuclMed 1991;32:1301—1309 The specific pathologic conditions in which nuclear
medicine may play a role are listed in Table 2.
In reviewing procedures of my choice in renal nuclear
medicine, it is necessary also to evaluate these procedures
he most important concept in studying the kidney is in relation to radiographic and other diagnostic imaging
a recognition of the intimate relationship between struc procedures. The complementary modalities to be consid
ture and function. Although procedures which are primar ered are ultrasound, urography, angiography, and corn
ily functional and procedures dependent on imaging are puted tomography (CT). At this time, there are few data
discussed separately here, no renal study can be evaluated that would support the utilization of magnetic resonance
properly without considering its physiologic basis. Table 1 imaging (MRI) in the routine clinical evaluation of the
lists the major radionuclide procedures available in uro kidneys and urinary tract. This area ofapplication of MRI
nephrology. has been a great disappointment so far, but continues to
Among the clearance methods, the continuous infusion be an area of active investigation.
technique has been and continues to be a major method
for investigational studies where accurate and precise RADIOPHARMACEUTICALSFOR RENAL STUDIES
measurements of renal function are needed. The use of The radiopharmaceuticals that have been used for kid
continuous infusion clearance in clinical practice is limited ney studies are shown in Figure 1.
and will not be discussed here. The single injection clear
ance methods offer the great advantages ofsimplicity, ease Glomerular Filtration Rate
of performance, low radiation dose, and reasonable accu The radionuclide agent of choice for an extremely ac
racy. curate measurement of the glomerular filtration rate
Radiorenography has evolved into a complex technique. (GFR) is 51Cr-EDTA(1). This agent is not available in the
Captopril renography is being used with increasing fre U.S., but it is widely used in Europe. The clearance of 51C-
quency while exercise stress renography may prove to be EDTA is virtually identical with the clearance of inulin,
of value in the future. Among the pharmaceuticals for therefore, it is a true GFR marker. In the U.S., 1311
renal imaging, 99mTc..glucoheptonate and @mTc@DMSAiothalamate has been used in its place. Technetium-99m-
have very different mechanisms of renal handling than DTPA has a clearance rate approximately 5% less than
99mTcDTpA (excreted by glomerular filtration), and that of inulin (2), which usually is an acceptable error in
99mTcMAG and ‘311-hippuran (excreted primarily by tu clinical practice. The error of serum creatinine is in the
bular secretion). Technetium-99m-MAG3 has been ap range of 10% or 15% in estimating GFR and may be
proved recently by the FDA and is available for routine greater in renal failure. Technetium-99m-DTPA yields an
applications, although pediatric use of this agent has not estimate of the GFR within 5% of the true GFR. It is
yet received approval. inexpensive, has a low radiation dose, and, most impor
The radionuclide cystogram has achieved widespread tantly, it can be usedfor renal imaging, making it the GFR
application in the evaluation of ureterovesical reflux. The agent ofchoice overall in clinicalnuclear medicine practice.
TubularSecretion
Received Nov. 14, 1990; revision accepted Mar. 27, 1991.
For reprintsContact:M. DonaldBlaufox,MD,PhD,AlbertEinsteinCollege Iodine-131-hippuran is currently the agent of choice for
of Medicine, 1300 Morris Park Ave., Bronx, New York 10461. estimating effective renalplasmafiow (ERPF). Iodine-123-

Procedure Choices in Renal Nuclear Medicine •


Blaufox 1301
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TABLE I
@ Lkonephrologic Procedures in Nudear Medicine TUSULARRE8ORpflCH
@To@schniS@•
..@
.
.. OLOMERULARFILTRAT1ON
I “@
“c@
@
@
1. ClearanceMethods 5. RadiOnUclidecystogram “•,_.
‘@‘I4S8A ___
I I
A. Continuous
infusion A. Residualurine c __J“cl'EDyA
\ —
B. Singleinjection B. Ureterovesicalreflux I
“0LfrOTPA

I @To@OT@
singleinjec 6. Scintiphotography
C. Simplified I @@4-OA@@s
tion A. lndMdualrenalfunction ri
D. In vivocamera tech 1. 131l_,
lssl@hippuran CORTEX

niques 2. @“Tc-DTPA Tueu@ReEcRE@Ow.


2. Radioimmunoassay 3. @Tc-MAG3 EFFECTRERENALPLAMAFLOW
3H. ‘@C@PAH
@
A. Angiotensin B. Individualrenalmass IR,@

B. Renin actMty 1. @Tc-DMSA


C. 2. @“Tc-glucoheptonate
3. Radiorenography C. Perfusionimaging
A. @“1c-DTPA 1. Anylow-dose @rc
agent
B. ‘31―@I-hippuran D. Morphology
C. 1. Renalmassagents MEDULLA
Tueu@RRXATmN.
@MOR@OLOOv

D. Miscellaneous 7. Renal blood flow


4. Body spaces 8. Genitalimaging
A. Penilebloodflow
B. Testicular perfusion

hippuran has a lower radiation dose, and so it is theoreti


FIGURE1. Graphicdepictionof the areasof the nephron
cally preferable to 1311,but because ofcost limitations and where various radiopharmaceuticalsare handled. Those phar
a short shelf life, the 1311agent is the most practical for maceuticalsthat are consideredto be agentsof choiceare shown
measuring ERPF. Technetium-99m-MAG3, which has inbold.
only been available for a relatively brief time in the U.S.,
may assume a major role in evaluating tubular secretion.
MAG3 is significantly different from hippuran in that
Static Imaging Agents
MAG3 apparently clears at a rate lower than ‘31I-hippuran
Technetium-99m-DMSA and @mTc@glucoheptonate are
(about 80%) because it is not filtered by the glomerulus
the two major agents available for renal parenchymal
(4). Although it has lower clearance values, MAG3 is taken
imaging. These two radiopharmaceuticals are very differ
up in very high quantities, gives excellent renal images,
ent. A significant portion ofglucoheptonate is ifitered (5),
and has moved rapidly into routine practice. The small
so that in patients with urinary tract obstruction, the
difference in excretion characteristics may be of value in
accumulation of glucoheptonate in the collecting system
some situations where it is desirable to evaluate pure
can present a problem in interpreting parenchymal images.
tubular secretion. Hepatic excretion ofMAG3 is a problem
In patients without urinary tract obstruction, the filtered
that may interfere with its use in single injection clearances
component is not a problem and it can be advantageous
at low levels of renal function. Clearance techniques that
in providing additional information about the collecting
include urine collection avoid this problem.
system.
Technetium-99m-DMSA is handled by a very different
TABLE 2 excretory mechanism (6). Glucoheptonate shares the en
NuclearMedicinein GenitounnaryDisease zyme system for para-amino-hippuric acid and 131I-hip
Acute renal failure
puran in the proximal tubules, while 99mTcDM5A is cx
Chronicrenalfailure creted by a different process. It is concentrated to a greater
Con@ anomahes extent (about 40% ofit is accumulated in the kidneys) and
Epididymitis as a result 99mTcDM5A delivers a much higher radiation
Impotence dose (per MCi administered) to the kidney than 99mTc@
MassLesions
Pyelonephritis
glucoheptonate. If a renal perfusion study is needed in
Quantitationof renalfunction conjunction with a static imaging study, @mTc@glucohep
Renalperfusion
abnOrmalities tonate is suitable because of the lower radiation dose.
Renaltrauma Technetium-99m-DMSA should not be used for flow stud
Renovascularhypertension ies, but it is an ideal agent for extremely detailed renal
Residualurine cortical images. The best way to minimize radiation dose
Testiculartorsion
Transplantation and perform a flow study in patients in whom perfusion
Ureteralvesicalreflux imaging is needed in concert with static imaging is to do a
Urinarytract obstruction flow study with @mTc@DTPAfollowedby a static study with
Varicocoele 99mTcglucoheptonate, or if very fine resolution is needed,

I 302 TheJournalof NuclearMedicine•


Vol. 32 •
No. 6 •
June 1991
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followed by 99mTcDMSA Quantitative separated renal ERPF: in vitro 1 sample method ( fl ) vs.
in vitro 2 sample method (I)
function studies may be performed with DMSA. Many 800

@
centers use a single dose of glucoheptonate for the perfu 700
sion and imaging study. A number of centers use gluco
@ 600 • • •••
• •
heptonate instead of DMSA for quantitative imaging.
S . •
Gallium may be considered as a renal agent when used @5oo. S

@ in studying pyelonephritis or renal abcess. Monoclonal 400


antibodies and indium-labeled white cells have not proved
practical for renal imaging and are not discussed here,
E 200 @-.-—-.--@ y(fl)—O.850X(I)-73
@ although they are still being actively investigated. n-41

@ CLEARANCEMETHODS I I I II
100 200 300 400 500 600 700 800
The clearance techniques currently available include: ERPF(mi/mm)by in vitro2 samplemethod

compartmental analysis methods, which require four to


six blood samples; simplified models (single-compart FIGURE2. Correlation betweenmeasurements of effective
ment), which require only two samples; a further simplified renal plasma flow using the in-vitro one-samplemethod versus
model, which utilizes one sample; and several gamma measurementsusing the in-vitro two-sample method. The cor
camera external counting methods, which require no relation is excellent supporting the close relationshipand accu
plasma samples. The question repeatedly asked is: “Which racy of both methodologies.(Reprinted with permission from
reference28, Fig. 2).
one of these techniques should I use?―Besides these pop
ular methods, numerous others have been described. All
of these techniques work, but they differ in their advan 99mTcDTPA There is not yet a body of data as extensive
tages and disadvantages. for GFR measurements as currently exist for ERPF meas
Multi-compartmental systems (more than two compart urements using one sample. At this time, a conservative
ments) add little or nothing to the accuracy of clearance approach calls for measurements of GFR using a two
techniques. The two-compartment model appears to pro sample method drawing theplasma samples at about 120—
vide the most accurate measurement of renal function 180 mm if possible but no earlier than 100 mm after
when an agent is used for single injection clearance and injection (10). This approach is applicable to children,
requires about six blood samples. Technetium-99m-DTPA although the best time to draw the samples is widely
or ‘31I-hippuran
may be used for accurate estimates of the debated.
clearance ofthese agents (7), but the technique is probably The one-sample method does not appear to be applica
more accurate than necessary for most clinical situations. ble for use in children due to the rapidly changing rela
Although techniques requiring urine collection avoid the tionships in body compartments and body size and in
assumptions of disappearance methods, they do not ob renal function itself. The assumptions needed for a single
viate urine collection which is cumbersome. Therefore, sample technique may be erroneous unless a curve is
they will not be discussed further. constructed for every age or level of renal function. There
The simplified model has a role in clinical practice and fore, in studying children, the two-sample method remains
so do the single-sample and the gamma camera methods. the technique ofchoice. Table 3 lists the normal values for
The two-sample method is quite simple. Two blood sam renal function at several age levels.
ples are obtained for 311-hippuran, one at about 30 mm Figure 3 shows the correlation between the two-sample
and one at 40 mm. The rate ofdisappearance ofthe isotope method and external measurement ofERPF. Considerable
is used to estimate renal clearance, which is calculated scatter also is shown. In switching from a blood sampling
from the product of the slope of the exponential disap technique to an external counting technique, a wider range
pearance and the volume of distribution (8). The single of error is introduced. Any external counting technique
sample method requires only a single blood sample drawn will be significantly less accurate than a technique using
at about 44 mm (for hippuran). This sample is assumed blood sampling.
to fit to a known parabolic or exponential function to Among the external counting techniques for evaluation
calculate the clearance. The relationship between the one of individual renal function, the initial slope method has
sample clearance method and the two-sample clearance not been as reliable as the integral method in my experi
method (Fig. 2) is excellent. If an adult study requires ence. The results appear to worsen with background sub
measurement ofERPF, then my procedure ofchoice is a traction. The great variability ofthe slope method and the
single 44-mm sample ofplasmafitted to the Tauxe equa error introduced by background subtraction (although the
tion. This method yields accurate measurement of ERPF literature suggests otherwise) are serious limitations (11).
in adults, but it may not be reliable in children. The integral method for individual renal function is my
Several investigators are working now on the application procedure ofchoice. It should be emphasized that there are
of the single-sample technique to measure GFR using many strong proponents of the slope method whose cx

Procedure Choices in Renal Nuclear Medicine •


Blaufox 1303
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TABLE 3 integral methods are used without background subtraction.


NormalValuesfor RenalFunctionat SpecificAges It is the reproducibility of the results that usually is most
(mI/mm/i.73 m@)
important clinically in following patients to see whether
Age Ci@ they have significant changes in renal function. I recom
mo16-6050-866—8mo60—12070—10920—29
<3 mend the integral of the count rate between 1 and 2 mm
or between 1.50 and 2.50 mm (13).
yr123
19530—391 ± 16638 ± Another major problem with quantitation ofrenal func
12340—49 19 ± 11592 ±
± 23 tion is due to variability of renal depth. Maneval has
13580—8965±20 ± published data showing that in children there is significant
50—59121 99±15494
variability in renal depth (14) among and between the
kidneys. Assumptions about kidney depth lead to error, as
Tablemodifiedfromreferences30 and 31. do the various equations to correct for depth. Theformula
Legend: The clearance values listed above were completed from correction for renal depth is not accurate. If individual
several sources in the references noted. Note the increasing values renalfunction is to be measured most accurately, we use
with age 20-29 yr followedby a declinerepresentinggrowth and the integral technique with no background subtraction and,
maturationintoadulthoodandthena progressivelossof functioning
nephrons.
ifpossible, correctfor measured renal depth. This may be
done with a camera technique using a lateral view or a
geometric mean. The best possible but least practical way
to correctfor depth is to measure the true renal depth with
periences differ from ours. Our studies suggest that the use ultrasound. Regardless of the approach used, renal depth
ofbackground subtraction introduces more problems than is a source of error and tends to make the measurement
it solves at relatively good levels of renal function. Re of individual renal function less accurate but not less
cently, Piepsz published a technique using multiple regions precise. The standard error of the estimate in external
of interest, combined to do background subtraction (12) counting techniques is about 20%. This is a significant
but this has not been confirmed. Values of separate renal error, but it is usually acceptable within clinical settings
function in patients with relatively good renal function, in where no other method yields individual renal function.
my experience, are less reproducible when background In the future, there may be more accurate methods of
subtraction is applied. It is not known what the best measuring individual renal function with camera meth
background region is, and there probably is no way to odology. Paramora (15) compared renal volume estimated
choose the true background. Results in patients with rea from SPECT versus DMSA uptake and demonstrated
sonable levels of renal function are highly reproducible if excellent preliminary results.

IMAGING TECHNIQUES
ERPF: in vivo csmera method (V) with background
adjacent to each kidney
in vitro 2 sample method (I)
vs.
Congenital Anomalies and Mass Lesions
800 Nuclear medicine has an important and a complemen
S
£ S •
@ 700 tary role with radiographic techniques in the evaluation of
ft
i@600 . congenital anomalies of the kidney. An important area is
S S
the differentiation between renal mass and a hypertrophied
@500
renal column or unusual shape. Although oncocytoma has
• • • S been reported to concentrate hippuran (16), tumors of the
j@300 S S
kidney rarely concentrate renal imaging agents. No malig
@
@
@
200
S
55 nant tumor has demonstrated uptake. The differential
S S Os ,—
&2 00 •S diagnosis between hypertrophied column, congenital mal
U'
I 1 I I I I formation and tumor may not be resolved with ultrasound.
100 200 300 400 500 600 700 800 The procedure of choice in the dj/Jerential diagnosis be
ERPF (mi/mm) by In vitro 2 sample method
tween hypertrophied column, unusual renal shape, and
intrarenal tumor is a glucoheptonate or DMSA scan. UI
FIGURE3. Correlationbetweenthe in-vitrotwo-sample
methodand in-vivomethodsfor measuringeffectiverenalplasma trasound provides complementary information.
flow with external camera techniques. Although the correlation is Among the other congenital anomalies, horseshoe kid
excellent, notice the very wide scatter compared to the scatter ney, which is difficult to image by radiographic techniques,
shown in Figure 2. The accuracy of the in-vivo technique is may be evaluated with radionuclides. It may be deter
considerablyless than that of the in-vitro technique becauseof mined easily with radionucide imaging if the tissue over
the problems posed by variations in renal depth, background
contribution, and the numerous assumptionswhich have to be lying the spine represents functioning renal parenchyma
made for the technique. (Reprintedwith permissionfrom refer or is simply a fibrous band.
ence 28, Fig. 5). Other mass lesions are not in the domain of nuclear

@ 1304 The Journal of Nuclear Medicine Vol.32 No. 6 June 1991


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medicine at the present time. There may be future poten Diagnosisof ObstructedVersus Nonobstructed
tial for nuclear medicine's role in tumor evaluation. In a Dilatation
study by Williams, which evaluated the use of SPECT to The differential diagnosis ofthe significance of ureteral
determine mass lesions of the kidney, small lesions repre dilatation is best evaluated with the lasix renogram.
senting true-positive findings significantly increased with O'Reilly has now defined his procedure ofchoice (18). In
tomography compared with planar imaging (1 7). Nuclear performing lasix renography, I prefrr his approach which
medicine's role in neoplastic disease of the kidney cur is to read a baseline renogram, and ifthere is evidence of
rently is only secondary. a delay in the excretion of the radiopharmaceutical to
administer the lasix 15 mm prior to a repeat renogram.
UñnaryTract Obstruction Several alternative approaches appear to be reliable, but
Nuclear medicine is the technique of choice for evalu they have not had as much controlled study. Most cases
ating the patient once the anatomic diagnosis of ureteral will show a clear cut obstructive or nonobstructed curve
or pelvic dilatation has been made using a radiographic using this approach, and the number of equivocal re
procedure or ultrasound. The information not obtained sponses appears to be reduced. It is important that if an
by ultrasound or urography is the functional significance equivocal response is obtained the interpretation should
of the observed dilatation. The most important consider be exactly that. The patient should be studied again in 3—
ation may be to determine if the lesion represents signifi 6 moto evaluate
anychange
in renalfunction.
If renal
cant obstruction that will have an adverse effect on overall function is stable, there is no urgency to intervene.
renal function. Nuclear medicine techniques to determine If the urinary tract is clearly obstructed and the patient
the individual renal function provide an important base cannot handle a significant load of fluid, then there may
line and a sensitive follow-up. be an indication for surgical correction. In patients with
The Whitaker test, for example, yields information very markedly reduced renal function, lasix may not cause a
different from that provided by scinti-imaging. Some phy diuresis and this should always be kept in mind as a
sicians believe that the Whitaker test is all that is needed potential source of error. In this situation the only test
to evaluate obstruction and to determine its functional available to determine the integrity of the urinary tract
significance. The Whitaker test involves intubation of the may be the Whitaker test. Lasix renography with 99mTc.
kidney and the infusion of saline at a controlled rate MAG3 appears to yield results that are quite similar to 131I
(usually about 10 ml/min). The normal rate of the urine hippuran (Fig. 4). Technetium-99m-MAG3 has the advan
flow is only 0.5 ml/min and may reach levels of 10 ml! tage of yielding excellent images of the collecting system.
mm only during periods ofextreme diuresis. So the urinary Technetium-99m-DTPA is an alternative agent, but it has
tract is severely stressed by the Whitaker test. I believe that a higher background.
the significant question is not whether the urinary tract There is an ongoing study by the pediatric nuclear
can deal with a high urine flow rate, but whether the medicine group to evaluate lasix renography in children.
urinary tract under normal circumstances is handling the The problem they have encountered is the increasing
volume load presented to it and whether there exists an number of neonates born with antenatal diagnoses of
adverse functional effect for the kidney's inability to han dilatation of the urinary tract as a result of the increased
die large volumes of urine flow. use ofultrasound in these patients. Ultrasound only shows

iac.

I.e.

7SS
FIGURE4. Lasixresponse
curvesin a patient who has
“C receivedan intravenousinjec
tion of @Tc-MAG3 (left)and a
second injection of 1@l-hip
as. puran(right)are shown above.
Lasix was administered in each
case at 18 mm and the two
curvesare quite similar.This is
a responsesuggestiveof non
significant ObstrUCtion. (Re
LASIX RESPONSE CURVES LASIX RESPOF4SE CURVES printed with permission from
Reference29).

@ ProcedureChoicesin Renal NuclearMedicine Blaufox 1305


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dilatation, but it does not differentiate if the dilatation is extremely important to note that in the presence of ob
functionally significant. Neonates lack maturity of the struction, the patient may have recoverable renal function.
kidney and so during the first 4—6wk after birth, the The newer cameras may cause problems with ‘311-hip
response to lasix may be unpredictable and the failure of puran imaging, and the technique has to be carefully
radioactivity to wash out of the urinary tract after admin standardized. An example of nonvisualization with hip
istration oflasix, theoretically, may not be due to obstruc puran is shown in Figure 5. After about 3 mo of nephros
tion of the urinary tract but may be a reflection of the tomy drainage, the patient had adequate renal function to
immaturity of the kidney. During the first 2 wk of life, sustain life. Therefore, if a new patient presents with
diagnoses ofobstruction using the lasix washout should be chronic renalfailure, the patient can either go directly to
interpreted with caution, and studies of neonates should ultrasound to rule out obstruction, or the patient can have
be delayed as long as practical. These recommendations a renal scan. Ifthe patient's kidneys are visualized, there
may change when the pediatric study data are available. is a potentialfor recovery, but obstruction still needs to be
ruled out. Ifthere is no visualization an ultrasound study
RenalFailure is mandatory. The absence of obstruction and renal vis
The azotemic patient with renal failure is at increased ualization suggests a poor prognosis. The presence of ob
risk oflosing some renal function as a result ofbeing given struction is an indication for surgical intervention even if
contrast media. This is particularly true in the diabetic the kidney does not visualize with hippuran. These state
patient. Diabetics with elevated serum creatinine levels ments are based on experience with ‘31I-hippuran.Tech
should be studiedfirst with nuclear medicine techniques or netium-99m-MAG3 has not been studied sufficiently to
ultrasound and only given contrast if it is required for make a general statement about nonvisualization with this
definitive diagnosis. Even non-diabetic patients with dc agent. Other radiopharmaceuticals have been used but
vated creatinine may show a further increase in creatinine they have not been studied as extensively.
after urography. Nuclear medicine can provide a relatively specific di
The choice between ultrasound and nuclear medicine agnosis in the patient with chronic interstitial nephritis.
depends upon the specific question being asked. Patients The typical appearance of chronic renal failure with a
whose kidneys do not visualize with hippuran are relatively delayed uptake is shown in Figure 6. There is activity in
uncommon, and this has important prognostic signifi the bladder, however, unlike acute renal failure, at 24 hr
cance. there is virtually no activity left in the kidney. The diag
In a study of 28 patients with nonvisualization, 16 had nosis is made by the administration of gallium which at
chronic renal disease and required dialysis within 6 mo, 5 72 hr shows intense uptake. Intense symmetric uptake of
had obstruction, 4 of these agreed to treatment and im gallium 72 hr or more after a renal scan in a patient with
proved, and 7 had acute renal failure and died (19). renalfailure is highly suggestive ofa diagnosis of interstitial
Nonvisualization with hippuran in the absence of obstruc nephritis (20). The gallium scan cannot reliably be inter
preted earlier than this because with azotemia there is a
tion is a poor prognostic sign. In chronic renal failure it
delay in the excretion of gallium by the kidney and the
suggests that the patient will need dialysis in a few months;
in acute renal failure the chance of death is high. It is uptake may be relatively intense.

FIGURE5. (A) A seriesof


images taken after the injec
tion of 131l-OIHin a patient @,.

with no evidence of renal


function is shown. The kid
neys cannot be identified
@
withany certaintyin any of .

the images. (B) Following


several weeks of catheter L. . I
drainage, the 1311-OlHstudy
is repeated in the same pa
tients after the bilateral ne
phrostomy tubes have been
removed. Note that now :@::4;
there is significantrenal up
take which is seen as early
as the 0—3-mm image with
progression into the collect
ing system and bladder
throughout the subsequent
images.

@ 1306 The Journal of Nuclear Medicine Vol.32 No. 6 June 1991


-@-@-@-
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@ L.v1r@ Transplantation
Renal transplantation is another area where radio
nuclides have achieved broad use. Characteristic patterns
of rejection and ATh have been described. In ATN, the
kidney is well perfused, there is little or no urine formation
and moderately good but delayed renal uptake of activity.
Rejection is associated with poor perfusion of the kidney,
poor renal uptake, but usually continued urine formation.
The differential diagnosis of rejection has been compli
cated by the widespread use of cyclosporin. No reliable
technique is routinely available to differentiate transplant
rejection from cyclosporin toxicity. Patency of the anas
tomosis can be assessed with a perfusion study, level of
function with ‘311-hippuran,99mTc@DTPA, or @mTc@MAG3,
FIGURE6. A seriesof imagesina patientwithchronic
renal and in patients suspected ofhaving urinary extravasation,
failure is shown above. Note especiallythe minimalvisualization
integrity ofthe urinary tract can be evaluated with @mTc@
of the kidney from 0 to 3 mm, suggesting a significantdelay in
glucoheptonate.
uptake, the increasedbackgroundactivity throughout the study
andthe persistenceof activityat 27—30 mm,whichis a resultof
Numerous approaches to evaluating transplants have
the delayedexcretion associatedwith probably a reduced urine
been reported. These include the use of indium-labeled
flow and some intratubularobstruction. red blood cells, gallium, and 99mTc..sulfur colloid. Although
I prefer the simple approach outlined above, the literature
should be reviewed for alternatives.
Infection
Professor Hertil from Frankfurt has obtained anti-T
Urinary tract infection is an area where nuclear mcdi
lymphocyte monoclonal antibody scans of normal trans
cine offers unique opportunities that have been largely
plants with no uptake in the region of the transplant.
underutilized. The urogram may appear normal in patients
Intense uptake occurred in patients who had ongoing
with infection involving the upper urinary tract. The dif
rejection ofthe kidney. This is a promising new application
ferential diagnosis between cystitis and renal infection is
difficult. Handmacher has shown quite clearly that in of radionuclides (Hertil A, personal communication). If
these studies are confirmed and if the patients tolerate the
patients with pyelonephritis, there are areas of non-uptake
agent, this could be an extremely important development
of DMSA due to the inflammation of the renal paren
in the role of nuclear medicine in renal transplantation.
chyma (21). Glucoheptonate also can be used in a similar
manner, and in patients who have abscess or localized
infection of the kidney, gallium can be extremely useful. Renovascular Hypertension
Differentiation of acute renal infection from cystitis can The standard technique for evaluating patients for re
be similarly useful in the patient with chronic disease in novascular hypertension involves combined imaging using
whom chronic changes may exist on a urogram (22). either ‘31I-hippuran
or 99mTc@DTPA and the generation of
DMSA imaging or glucoheptonate can be used to diagnose a time-activity curve to evaluate the relative rate of uptake
upper urinary tract infection. Gallium may be used to to and disappearance. Normally, the kidney uptake pattern
identify an abscess. These techniques are more sensitive should be symmetrical. Characteristically in a patient with
than urography. renovascuiar hypertension, there is a less rapid rate of
uptake by the involved kidney and the rate of washout is
RenalPerfusion slower. The disparity between the normal and abnormal
Nuclear medicine has a limited role in evaluating renal kidney depends upon the degree to which the abnormal
perfusion. We followed a patient with arterial venous kidney is affected. Bilateral disease presents a much more
fistula for more than 12 yr until she finally went on dialysis complex and unpredictable pattern, especially in the pres
in 1989. It was possible to follow the perfusion of the ence of significantly reduced renal function.
kidney with technetium flow studies and to avoid the need Images of the abnormal kidney usually show that it is
for repeat arteriography. Her renal function was followed somewhat smaller, picks up activity less rapidly, and at
by serial hippuran renograms. I believe that there are 27—30
mmtheimagecommonlyonlyshowstheabnormal
relatively few situations where a renal perfusion study is kidney, with the normal kidney having cleared. This pat
of great diagnostic importance. Arterial venous fistula of tern reflects the physiologic sequence of events in renal
the kidney, aortic obstruction, are a few, but in the vast artery stenosis where GFR is reduced, there is increased
majority of situations, one could probably not do a flow water reabsorption, and therefore there is a reduced rate
study and lose little information. Renal transplantation is of delivery of the radioactive material to the kidney and
the primary exception. Flow studies can be performed with reduced washout from the kidney because of the reduced
99mTcDTPA 99mTc@MAG3 or ‘23I-hippuran. urine flow rate. The technique is quite accurate with about

@ Procedure Choices in Renal Nuclear Medicine Blaufox 1307


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an 85% true-positive rate, similar to that reported by neous interpretation of the renogram. Sfakianakis has
McNeil and others for urography (23, 24). The problem suggested that errors in interpretation may be avoided by
is not its ability to detect renal artery stenosis, but rather giving all patients lasix as well as captopril (26). The
the high false-positive rate of about 10%, which also is renogram is a highly cost-effective procedurefor screening
equivalent to the urogram. This results in a large number for renovascular hypertension. Presently, my procedure of
of false-positives in a disease with a low prevalence. Al choice for captopril renography and for differential diag
though the technique has problems, it still is extremely nosis of renovascular hypertension is: to stop diuretics 5
useful in the differential diagnosis of renovascular disease, days prior to the test; stop other medications as soon as
and radionuclide techniques in particular play an impor possible; enalapril at least 3 days before; captopril at least
tant role in the follow-up of patients if an intervention is 2 days before; hydrate the patient in the department; give
performed. In determining whether a patient should have 25 mg ofcaptopril (some centers use 50 mgj—(crush the
digitalsubtraction angiography, the radionuclide technique tablet) 1 hr before the renogram (or enalaprilat i.v. 15 mm
helps to specify a patient population with a greater proba before). Thepatient must befasting; do curvesplus images;
bility ofdisease. Once the disease is diagnosed, angiogra use either DTPA, hippuran, or MAG3 according to your
phy then can be performed to detect renal arterial lesions. preftrence; optionally use lasix; @fthe renogram is abnor
Subsequently, the renogram can be usedforfollow-up using mal repeat the test without captopril (or enalaprilat) either
the initial test as the baseline, thus avoiding the necessity 6 hr lateror thenextday.
for postintervention angiography in determining the ade Numerous other approaches have been reported (27)
quacy ofthe intervention in restoring renalfunction. This and these should be reviewed before making a final choice.
is a highly cost-effective and useful approach that reduces RenalTrauma
patient exposure to contrast media toxicity. However, Evaluation for renal trauma with nuclear medicine tech
reducing the false-positive rate in screening for renovas niques has slackened due to the availability ofCT scanners
cular hypertension is still desirable. The captopril reno in emergency rooms, but nuclear medicine does have a
gram may have potential for accomplishing this goal. role in studying the functional consequences of renal
The generation of endogenous angiotensin within the trauma and in the follow-up of kidney recovery.
glomerular capillary leads to post-glomerular vasoconstric
Genital Imaging
tion in patients with renovascular hypertension. Because
Testicular scanning for torsion and epididymitis is the
perfusion pressure is reduced by renal artery stenosis, there
procedure of choice. Ultrasound does not approach the
is a tendency for GFR to fall, but by further constricting
reliability of nuclear medicine techniques except in a few
the post-glomerular arteriole, the pressure gradient across small studies. Nuclear medicine should not delay surgery
the glomerulus is maintained and GFR is restored toward but should simply help the surgeon make a decision.
normal. If a patient with renovascular hypertension is During the next few years, it appears that evaluation of
given captopril or another converting enzyme inhibitor, impotence with various nuclear medicine techniques will
the concentration of angiotensin in the glomerulus falls begin to become part of the armamentarium and may
and the compensatory effect of constriction of the post compete with selective arteriography because of its less
glomerular vessel is lost. This results in relative dilatation invasive nature and the more quantitative information
of the efferent arteriole with a reduction in the trans provided.
capillary gradient and a fall in GFR. This fall in GFR may Although available for many years, residual urine esti
be detected with radioisotope techniques. mates have been much underutilized in spite oftheir great
With the reduction of GFR after captopril, there is a accuracy. Because of the dangers and inconvenience of
dramatic worsening of function as shown by the renogram catheterization, the isotope test is preferablefor evaluation
curve, and this response to captopril may be interpreted ofresidual urine coupled with a renogram to evaluate the
as a positive and relatively specific test for renovascular upper tract, especially in patients with suspected prostatic
hypertension. Parameters which appear to be of use in disease. The increased availability of ultrasound to meas
captopril renography include global renal function meas ure residual urine may make this procedure obsolete cx
urement, relative renal function, urine specific gravity, cept in patients who are being imaged.
measurement of the blood pressure, and numerical analy For vesical ureteral reflux, the radiographic procedure
sis of the curves. The curves in patients with essential should be the first line of diagnosis. Because of the low
hypertension show little or no change post-captopril (25). radiation dose and high sensitivity, a radioisotope cysto
In about 20% of patients without renovascular hyperten gram is theprocedure ofchoiceforfollow-up and evaluation
sion, the scinti-images may reveal pelvic retention. This ofsurgical results. Indirect cystography has its advocates,
should not be confused with a positive test and cortical but it has not been studied as well nor is it as direct.
regions of interest should be generated to determine if
these curves are more normal. Inspection of the scinti FUTURE DEVELOPMENTS
images and generation of cortical regions of interest ap Some years ago, I proposed several areas for future
pears to provide sufficient information to prevent erro development in renal nuclear medicine. We already have

@ 1308 The Journal of Nuclear Medicine Vol.32 No. 6 •


June 1991
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made considerable progress towards immunologic imaging 9. Tauxe WH, Dubovsky EV, Kidd T Jr, et al. New formulas for the
calculation ofefl'ective renal plasma flow, Eur J Nuc/Med 1982;7:51—54.
ofthe kidney, definition ofthree ideal pharmaceuticals for 10. Russell CD, Bischoff PG. Kontzen FN, et al. Measurement of glomerular
GFR, ERPF and renal mass, and the use of SPECT for filtration rate. Single injection plasma clearance method without urine
quantitation of renal mass. For example, immunologic collection. J Nuc/ Med 198@:26:1243—1247.
I 1. Fine El. Captopril scintirenography. A protocol to assess efficacy and
imaging has been implemented for transplantation, early methodology. In: Blaufox MD, Hollenberg NK, Raynaud C, eds. Radio
studies for quantitation of renal mass with SPECT have nuc/ides in nephro-uro/ogy. Contributions to nephro/ogy, Vo/ume 79. Base):
been done, and presently we have @mTc-DTPA for GFR, Karger, 1990:211—218.
12. Piepsz A, Dobbeleir A, Ham HR. Effect of background correction on
‘3I-hippuranfor ERPF, and 99mTc@DMSA for renal mass, separate technetium-99m-DTPA renaiclearance. JNuc/Med l989;3l:430—
with very active work underway to identify further agents. 435.
The exact role of 99mTc@MAG3 will become clear in the 13. Dubovsky EV, RussellCD. Quantitation ofrenal function with glomerular
andtubular agents.SeminNuc/Med 1982;4:308—329.
near future, although its role as a pure tubular agent is 14. Maneval DC, Magill HL, Cypess AM, Rodman JH. Measurement of skin
unique. We desperately need convincing and carefully to-kidney distance in children: implications for quantitative renography. J
carried out efficacy studies ofnuclear medicine techniques Nuc/Med 1990:31:287—291.
15. Kawamurai, Itoh H, YoshidaO, Fujita1, TorizukakK. In vivoestimation
versus CT, ultrasound, and MRI. We need to define where of renal volume using a rotating gamma camera for @@mTc@dimercaptosuc@
nuclear medicine techniques fit in definitively with rela cinic acid renal imaging. Eur J Nuc/Med 1984;9:168—172.
tion to ultrasound and CT, since there are many centers 16. Lee VW, Foster Al, et a). Functional oncocytoma ofthe kidney: evaluation
by dual-tracerscintigraphy.J Nuc/Med 1987:28:1911—1914.
that utilize these techniques rather than nuclear medicine. 17. Williams ED, Parker C, Rankin D, Roy RR. Multiple-section radionuclide
Nuclear medicine has something unique to offer and hope tomography of the kidney: a clinical evaluation. Br J Rad l986;59:975—
fully these remaining problems will be resolved over the 983.
18. O'ReillyPH, BrittonKE,NimmonCC.Evaluationofurinary tract obstruc
next several years. There has never been as much attention tion. In: Blaufox MD, ed. Evaluation of rena/function and disease with
to renal studies in nuclear medicine as we are currently radionuc/ides. The upper urinary tract. Base): Karger, 1989:248—287.
witnessing. 19. Sherman PA, Blaufox MD. Clinical significance of nonvisualization with
@‘I-hippuran
renal scan. In: Hollenberg NK, Lange 5, eds. Radionuc/ides
in nephrology. Stuugart :Thieme; 1980:235—239.
ACKNOWLEDGMENTS 20. Wood BC, Sharma iN, Germann DR. ci a). Gallium-citrate imaging in
This work was supported in part by grant ROI-40566-03 from non-infectious interstitial nephritis. Arch intern Med l978;l38:1665—1666.
2 1. Handmaker H. Nuclear renal imaging in acute pyelonephritis. Semin Nuc/
the National Heart, Lung, and Blood Institute. The author also Med 1982;12:246—253.
thanks the many collaborators with whom he has worked over 22. Sty JR. WellsRG, Starshak Ri, et al. Imagingin acute renal infectionin
the years to aquire this data base. children.AiR l987;l48:472—477.
23. McNeilBJ, Varady PD, BurrowsBA,et a). Measuresof clinicalefficacy.
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Procedure Choices in Renal Nuclear Medicine •


Blaufox 1309
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Procedures of Choice in Renal Nuclear Medicine


M. Donald Blaufox

J Nucl Med. 1991;32:1301-1309.

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