Nuclear medicine techniques have become procedures of first choice in the diagnosis of renovascular hypertension and in the differential diagnosis of hydronephrosis. The author addresses the critical features of the most important and valuable renal radionuclide procedures currently in use.
is Professor of Clinical Nuclear Medicine at Albert Einstein
College of Medicine and Chairman of the Department of Nuclear
Medicine at Jacobi Medical Center.
is Professor of Nuclear Medicine and Chairman, Department of
Nuclear Medicine, Albert Einstein College of Medicine, Bronx,
In the past several years there have been a number of important
advances in renal nuclear medicine. In general, while the
improvements have been evolutionary rather than revolutionary, the
cumulative effect over 10 years has been substantial. Nuclear
medicine techniques have become procedures of first choice in the
diagnosis of renovascular hypertension and in the differential
diagnosis of hydronephrosis. Substantial consensus now exists for
many indications, protocols, and general methodology.
Quantitation of renal function has become easier, more
practical, and more accurate than ever using nuclear techniques.
The voiding cystourethrography (VCU) has become widespread in the
evaluation of reflux, and renal morphology studies have become
invaluable in children with pyelonephritis. Full descriptions of
all these techniques are beyond the scope of this article, however.
Many excellent reviews are cited here, including consensus reports
and practice guidelines and these should be consulted for greater
detail. Our objective is to provide selected comments regarding
critical features of the most important and useful renal
radionuclide procedures currently in use.
The most significant advance in radiotracer development in the
past 10 years has been the clinical application of Tc-99m
mercaptoacetyltriglycine (MAG3) as an all-purpose renal
scinti-imaging, function, and excretion agent.
Older function and excretion tracers continue to retain a role,
although to a lesser extent than previously. MAG3 effectively
eliminated the use of I-123 orthoiodohippurate due to the expense
of cyclotron production of the latter isotope. I-131
orthoiodohippurate retains a role in emergency studies due to its
long shelf life, although it is of value only in centers using
older gamma cameras still capable of imaging the 364 keV photopeak.
Tc-99m diethy-lenetriaminepentaacetic acid (DTPA) continues to be
used in many renal function/excretion studies, although it is
considered a second-line tracer in the presence of renal
dysfunction, and in the evaluation of obstruction. Tc-99m
glucoheptonate (GHA) and Tc-99m dimercaptosuccinate (DMSA) remain
useful in the evaluation of acute and chronic pyelonephritis.
Principle procedures and indications
Several renal radionuclide exams have become the first-line
procedures in the evaluation of specific clinical conditions. These
are indicated in Table 1. Diuretic renography
and captopril renography
are the subjects of several recent consensus reports, and practice
guidelines, whose major features are discussed below. Table 1 also
includes renal scintigraphy and cystourethrography in view of our
strong perception of substantially increased usage in recent
Other renal radionuclide procedures of significance are included
in Table 2. These include procedures that have achieved substantial
utilization in many institutions, but whose indications have not
yet achieved the level of widespread consensus.
Specific procedures addressed by major consensus
Captopril renography--Captopril renography has emerged as the
procedure of choice to identify renovascular hypertension in
patients with high blood pressure. Data have accumulated confirming
the specificity of the procedure in a variety of clinical
circumstances. Specificity is maintained using strict
interpretative criteria, even in renal insufficiency,
although sensitivity is reduced. Of great importance is the
procedure's value in predicting blood pressure improvement after
renovascular surgery (i.e., the hallmark of renovascular
hypertension [RVH] and its distinction from renal artery stenosis
An important consensus report
was followed in print by Procedure Guidelines
by many of the same authors and investigators. Recommendations from
these can be taken together as the definitive current state of the
art. They include:
a) Adequate hydration (250 to 500 mL fluid by mouth, at minimum,
30 minutes before tracer administration).
b) Discontinuation of diuretics for 1 week and preferably
(although not absolutely) ACE inhibitors (captopril 1 to 2 days;
enalapril, lisinopril and other longer-acting inhibitors 4 to 5
days). Other medications may be maintained without jeopardizing
interpretability of the exam.
Study methodology: a) 1- or 2-study using Tc-99m MAG3, or DTPA.
I-123 OIH and I-131 OIH are not as widely available, but are
acceptable tracers as well.
b) Baseline exam with 2 mCi (75 MBq) MAG3 or 3 to 5 mCi
c) 25-50 mg oral crushed captopril. (IV furosemide optional; IV
enalaprilat instead of oral captopril also optional); monitor blood
pressure for 1 hour.
d) Post-captopril study with same tracer as baseline, using at
least double dose.
a) A post-captopril unilateral reduction in renal uptake (seen
mostly with DTPA) or prolongation in parenchymal retention (any
tracer) are the most reliable criteria for identification of renal
artery stenosis causing renovascular hypertension. Qualitative
interpretation may be refined into probabilities of disease using
the Oei/Nally criteria (figures 1 and 2).
b) The only quantitative criteria that perform respectably
1) a unilateral increase by at least 0.15 in the 20/Pk value
post-captopril for MAG3 or or OIH (and probably for DTPA as
2) Tpk increase by >=2 minutes
3) a unilateral reduction in relative renal function by
No other quantitative criteria are definitely helpful.
Renal dysfunction (glomerular filtration rate [GFR] <50
mL/min), a small kidney, and bilateral disease all reduce the
sensitivity of the test, although specificity appears preserved if
a unilateral change in the renogram after captopril is strictly
adhered to as a diagnostic requirement.
An important pitfall to note is a bilateral and symmetric change in
the renogram after captopril. This finding is sometimes contributed
to by patient dehydration, although the cause is often not
determined. Regardless of circumstances, this must be considered a
non-diagnostic result, as most exams with this result do not turn
out to have bilateral renal artery disease.
Variations: The most common variation is to skip the baseline
exam under the premise that a normal post-captopril exam ends the
search for RVH. While this is true, an abnormal exam usually
mandates recalling the patient for a "baseline" study on another
day. Therefore, any pre-test circumstance that increases the
likelihood for an abnormal renal exam pushes examiners toward
performing baseline and post-captopril on the same day (Table 3).
The baseline exam should definitely be performed if the pre-test
risk for RVH reaches 30% or more.
In patients for whom there are very few risk factors for RVH, the
convenience of omitting the baseline exam may be practical.
Diuresis renography--Twenty years after its introduction,
diuresis renography continues to be a highly valuable clinical
standard for assessment of renal outlet obstruction among patients
with incidentally discovered hydroureteronephrosis. It is important
to distinguish true outlet obstruction from among the
non-obstructive conditions that may be associated with
hydronephrosis (Table 4). Limitations on the procedure exist in
patients with renal dysfunction and severe hydronephrosis in whom
an insufficient diuretic response may be misleading or
non-diagnostic. In addition, an optimal technique has evolved over
the years owing to attention to many well documented technical
Preparation: Adequate hydration is very important. In adults,
the dehydration that commonly accompanies an early morning study
(particularly in patients who mistakenly think that all medical
tests should be performed after an overnight fast) generally should
be addressed by administration of 250 to 500 mL of fluids 30
minutes before the study. In small children, additional intravenous
hydration is recommended.
Bladder catheterization also is needed in small children (i.e.,
those who cannot be relied on to void on command) to permit
adequate urine flow.
Tracer: The tracer of choice has become Tc-99m MAG3 due to rapid
clearance from the blood and consequent prompt filling of the renal
pelvis. DTPA, in many patients, is cleared from the plasma too
slowly and, therefore, fills the pelvis too gradually to permit
adequate assessment of pelvic drainage.
Diuretic: The consensus recommendation calls for intravenous
administration of 0.5 mg/kg furo-semide (1 mg/kg up to 2 years old)
at 20 or 30 minutes after administration of the radiotracer (often
identified as F+20 or F+30, respectively).
Interpretation: A brisk response to furosemide usually can be
gauged scintigraphically (figure 3). In addition, the response
should be assessed by the renographically determined renal pelvic
time to half-emptying, using a renal pelvic region of interest. A
value of 12 to 15 minutes or less may be interpreted as a normal
value. One should bear in mind, however, that slavish reliance on
this number may be misleading. For example, renal dysfunction,
dehydration, and severe pelvic dilatation all may contribute to a
prolongation in the half-emptying time to furosemide without the
presence of obstruction. It's best to recognize that <10 minutes
is clearly normal, 10 to 15 minutes is probably normal, and >20
minutes is abnormal. Values between 15 to 20 minutes should be
interpreted with caution, and may require sequential studies to
diagnose obstruction by the deterioration in renal function. Other
pitfalls in technique that can also misleadingly suggest
obstruction include infiltration of either the tracer or the
diuretic. The former can be detected by an image of the injection
site, or a rising background curve.
Variations: The peak action of intravenous furosemide is usually
about 20 minutes after administration. Therefore, the absence of a
brisk diuretic response following furosemide should prompt a repeat
study with furosemide administered 15 minutes prior to the
radiotracer (so-called F-15 study; figure 4). Unobstructed kidneys
will have normal renograms using this approach. (A minority
recommendation in a consensus paper was to dispense with the F+20
study altogether in favor of the F-15 study for all patients.
This approach has merit, although it should probably be reserved
for experienced practitioners). Recently there has been support for
a study giving furosemide simultaneous with the radiotracer.
Detection of renal infection and scar--Both GHA and DMSA have
been shown to be of value in demonstrating regions of acute and
chronic renal infection in children and adults.
Evidence has accumulated showing the progression of repeated bouts
of acute pyelonephritis with the development of scars.
The value of scinti-imaging is in early detection of abnormalities,
especially since data are available demonstrating healing of
scintigraphic defects associated with successful early antibiotic
Acute pyelonephritis is associated with regions of hypofunction
manifested as intraparenchymal defects. Renal contour abnormalities
or other morphologic distortions due to scar most commonly reflect
chronic pyelonephritis. In acute or chronic presentations,
scintigraphy has very high sensitivity (>90%) for detection of
infection or scar. The relative value of planar vs SPECT imaging is
somewhat controversial, as some investigators have found increased
sensitivity of SPECT to introduce artifactual defects.
Nonetheless, even with planar imaging, the studies show remarkable
and sensitivity easily exceeds IVU, sonography, and CT. Spiral CT
may be competitive, but data are still lacking.
Voiding cystourethrography--The voiding cystourethrogram remains
valuable to document and follow ongoing reflux, a known contributor
to renal infection and scarring.
The radiologic and radiotracer versions of this procedure are quite
similar, with a slight edge in sensitivity going to contrast VCU
for grade I and II reflux and to the radionuclide study for grades
III to V. Institutional practices usually determine whether a
child's first diagnostic VCU is performed with contrast or tracer.
Regardless, follow-up usually is performed with the radionuclide
procedure due to much lower radiation absorbed dose. Identification
of reflux in a child with scarring signals the need for corrective
surgery to stop the reflux of urine.
Measurement of renal function Nephrologists have become
increasingly interested in accurate evaluation of GFR in a variety
of clinical situations. A common example is in the sequential
evaluation of renal transplant patients on renotoxic drugs.
Creatinine clearance determinations are generally compromised by
urinary collection difficulties. Clinically useful formulas to
determine GFR have been developed based only on serum creatinine
concentrations together with the patient's age and weight, but more
accurate still have been single sample DTPA clearance
Measurement of renal function is more difficult to standardize
in children. This difficulty is reflected in the lack of consensus
that still exists regarding measurement methods.
Total renal function can be quite easily measured using single
blood sample methods. These techniques are approaching consensus
for measurement of GFR using Tc-99m DTPA. In adults, formulas have
been developed that accurately determine GFR from a single blood
sample drawn at about 3 hours after injection.
In children, consensus has been harder to reach, principally
because it is more difficult to establish norms in children.
Individual renal function remains the unique province of nuclear
medicine among non-invasive techniques.
The simplest procedure that has gained consensus, using MAG3 or OIH
R (%) = R/(R + L)
Where R is the summed counts within the right kidney region of
interest from 60 to 120 seconds and L is the same for the left
kidney. Using DTPA, the same formula applies, but the counts are
best obtained from 90 to 150 seconds.
Critical to correct performance of this simple equation is that
the correct time of integration is: a) performed before 150 seconds
to minimize contribution of pelvic excretion; b) begun at no sooner
than 60 seconds to minimize the contribution of blood background;
and c) The use of background subtraction is generally done with
lateral semi-lunar crescent regions of interest normalized to the
area of the respective renal region of interest.
Exercise renography: The association of abnormal renal function
during upright bicycle exercise has been found in up to 50% of
individuals with early essential hypertension with no other
evidence of renal disease. This suggests a possible causative role
of the kidney in some individuals with essential hypertension. This
line of evidence, while provocative, has yet to be fully evaluated.
Aspirin renography: Aspirin, a prostaglandin E2 inhibitor, has
an enormous range of uses; one of which is to cause reduced urine
production in a kidney affected by RVH. The effect on the renogram
is similar to that of captopril, and the sensitivity and
specificity may be comparable, although these data are available
only in small series.
Evaluation of impotence: Techniques have been developed using
gamma camera scinti-images with computer quantitation of blood
washout as well as with lightweight highly sensitive bedside
These have not yet become routine, although a great deal has been
learned about the physiology of erectile incompetence.
It is clear that renal radionuclide procedures have assumed
major roles in the evaluation of several important clinical
conditions affecting children and adults. In most instances, the
aspect of the radionuclide test that sets its value apart from a
competitive imaging exam is the functional information revealed.
This can be seen explicitly in captopril renography, where the
physiologic significance of a given anatomic stenosis is assessed
by its effect on the renin angiotensin system. Similarly, diuretic
renography tests the physiologic significance of a given anatomic
dilatation. Somewhat less obvious is the remarkable superior
sensitivity of GHA and DMSA renal morphology studies in
pye-lonephritis compared with most anatomic imaging; although here
spiral CT may end up playing a larger role in the future.
Additional functional tests on the horizon maintain attention on
the value of renal radionuclide procedures well into the
foreseeable future. AR