Nuclear Renal Imaging in Acute Pyelonephritis
Hirsch Handmaker
Patients with acute pyelonephritis may present with
a spectrum of clinical signs and symptoms. There are
f e w noninvasive diagnostic studies, however, to confirm or exclude this diagnosis. A small number of
patients, generally those with severe disease, will
demonstrate radiographic changes on excretory urography, but the lack of sensitivity of the IVP in early,
acute pyelonephritis is well documented. Several
radionuclide techniques have been proposed to
assist in the earlier detection of this clinical problem
including imaging with Mercury-197 chlormerodrin,
Gallium-67 citrate, Technetium-99m glucoheptonata, Technetium-99m DMSA, and, more recently,
Indium-111 labeled white blood cells. The success of
the renal cortical imaging agents as well as those
which localize in infection are described in this
report. There appears to be a complimentary role for
the cortical imaging agents and the radiopharmaceuticals which localize in bacterial infection. Cortical
agents offer the advantage of specific assessment of
functioning renal tissue and a convenient, rapid
method for following the response to treatment in a
noninvasive manner. A pattern is described which
may be diagnostic; correlation with Gallium-67
citrate or Indium-111 WBCs may increase the probability of infection as the cause for the cortical abnormality. The measurement of differential renal function using cortical agents provides additional information to assist the clinician in predicting the late
effects of infection. Improved sensitivity and specificity, and a reproducible method for following the
response to therapy in patients with acute pyelonephritis are the advantages of the techniques
described.
"Pyelonephritis, like virtue, is easier to talk about
than to define."
origin" with little to suggest the kidney as the site
of infection. Conventional radiographic and
ultrasonic examinations generally are accepted
as of limited value in acute pyelonephritis;
nuclear medicine procedures rarely are mentioned in review articles dealing with imaging
strategies in patients with sudden onset of fever,
flank pain and pyuria/bacteruria.2 This review
summarizes the use of nuclear renal imaging in
acute pyelonephritis and its efficacy.
Edward H. Kass ~
CUTE bacterial pyelonephritis produces a
A variety of problems for primary care physicians, pediatricians, and diagnostic specialists.
The seriousness of the disease is punctuated by
the evidence that chronic renal disease may be a
frequent late result of acute infection and the
possibility that a direct relationship exists
between acute pyelonephritis and renal hypertension. It often is difficult to confirm or exclude
renal parenchymal involvement by a bacterial
infection on the basis of the patients clinical
presentation. Fever, leukocytosis and bacteriuria
alone do not differentiate simple infection of the
bladder and/or ureters from actual renal involvement. Conversely, patients with acute pyelonephritis may present as a "fever of unknown
From the Nuclear Medicine Service, Children's Hospital
of San Francisco, San Francisco, Calif.
Address reprint requests to Hirsch Handmaker, M.D.,
Nuclear Medicine Service, Children's Hospital of San Francisco, 3700 California Street, San Francisco, Calif. 94118.
Portions of this work were originally presented at the 26th
Annual Meeting of the Society of Nuclear Medicine in June,
1979.
Supported in part by General Research Support Grant 5
501 R R 05470-08 and funds made available by the Board of
Directors, Children's Hospital of San Francisco.
91982 by Grune & Stratton, Inc.
0010-2998/82/1203-0003501.00/(9
246
M A T E R I A L S A N D METHODS
Several radiopharmaceuticals have gained support for use
in the diagnosis and evaluation of inflammatory diseases of
the kidney.
Gallium-67 citrate is injected intravenously in a dose of
3-6 mCi (5 0 #Ci/kg) or according to height and weight
tables when used in pediatric patients. ~ Some authors have
advocated the early (6 hr) imaging of patients suspected of
having acute pyelonephritis.4 We prefer to wait 24-48 hr
because of the significant normal renal uptake and excretion
which occurs in the first 24 hr and may interfere with the
proper evaluation of the kidneys. Current scintillation
gamma cameras using multiple photopeak techniques provide high quality images despite the multienergy emissions of
this radiopharmaceutical. Tomographic scanners or other
tomographic devices may reduce interpretive difficulty but
are mentioned in only one publication on this subject. 4
Renal cortical imaging can be accomplished with either
the intravenous injection of Technetium-99m glucoheptonate, in a dose of 10-15 mCi, again adjusted for height and
weight in pediatric patients, or Technetium-99m DMSA, 3-5
mCi in adults and similarly adjusted for pediatric patients.
Dynamic perfusion images in a posterior position are
useful in evaluating the perfusion and function of the kidneys.
No specific perfusion pattern is seen in acute pyelonephritis;
increased blood flow may occur.
Seminars in Nuclear Medicine, Vol. XII, No. 3 (July), 1982
NUCLEAR RENAL IMAGING
Recording of the dynamic and static images on computer
systems should be an adjunct to the study; quantitative
information can be obtained, particularly with the Technetium-99m DMSA s!udy, and may be of value in assessing
patients in the acute and recovery stages of acute pyelonephritis.
After an appropriate delay, generally 90-120 min after
injection, the highest possible resolution images are obtained
using a high resolution parallel hole low energy collimator
and posterior oblique pinhole views as has been described
elsewhere. 5 Pinhole views are essential to delineate the striking pattern of acute pyelonephritis.
Indium-Ill labeled autologous white blood ceils have
recently been introduced as a method for evaluating acute
pyelonephritis. 6 The WBC's are injected intravenously,
usually 500 ~Ci-lmCi, and imaging is performed at 18-24
hr.
247
G A L L I U M - 6 7 CITRATE
RP 2 7
RESULTS
We have had the opportunity in the past 6 yr to
evaluate over 60 patients to confirm or exclude
the diagnosis of acute pyelonephritis. Patients
studied were from 1 wk to 50 yr of age, and had
clinical findings ranging from "fever of undetermined origin" to bacteruria, flank pain and renal
colic. Ten of these patients had abnormal renal
cortical scans that assisted in confirming the
diagnosis of acute pyelonephritis. Five of these
patients with abnormal cortical scans also had
abnormal Gallium-67 citrate images. No
attempt was made to perform both Gallium-67
citrate and renal cortical imaging studies in all
patients in this series. There were no false negative renal cortical studies in our series.
Figure 1 demonstrates the findings in a 27yr-old female with right flank pain, fever, bacteruria, and pyuria. The 48-hr Gallium-67 citrate
scan was suspicious for increased uptake in the
region of the right kidney but background activity in the abdomen made it difficult to confirm
the diagnosis of acute pyelonephritis. Drip infusion nephrotomogram and IVP were normal. A
renal cortical study was performed with Technetium-99m DMSA which revealed a focal defect
in the mid-portion of the right kidney, with an
abnormal left-to-right uptake ratio. The right
posterior oblique pinhole view revealed a distinctive striated "flare" defect in the perihilar region
of the right kidney. This pattern was observed in
4 of the 10 abnormal patients. The right kidney
defect disappeared following 2 wk of antibiotic
therapy and on the repeat study the left-to-right
ratio had returned to nearly normal.
Figure 2 demonstrates the studies in a 9-
R
Anterior
9/6/74
t R
L/R = 1.27
,~
t
RP 27
......
9
]
k
"LPO
PO,te.or
Posterior
RPO
Posterior
RPO
11/11/74 L/
O
LPO
Fig. 1. A 27-yr-old female with right flank pain, fever
and pyuria. (A) 48-hr Gallium-67 scan shows increased
uptake in the right renal area; abdominal activity, liver and
contralateral renal uptake made confirmation of infection
difficult. (B) Tc-99m DMSA images on September 6, 1974
following gallium scan reveal right midrenal defect; pinhole
oblique suggest "'flare" pattern (see Discussion). Followup
scan after treatment on November 11, 1974 reveals return
to normal appearance. Quantitative ratios similarly show
return of function ("L/R').
mo-old male with recurrent urinary tract infections, pyuria, and fever. His excretory urogram
reveals delayed visualization on the right with
some dilatation of the right collecting system at
15 min. The 48-hr Gallium-67 citrate study
shows diffuse increased activity in the entire
right kidney compatible with either acute pyelonephritis or perinephric abscess. The Technetium-99m DMSA study demonstrates multifocal
248
HIRSCH HANDMAKER
79~00.003:
15 minutes
79-00-003
9 m o . O~
i: LPO
Posterior
RPO
Fig. 2. A 9-mo-old male w i t h recurrent urinary t r a c t
infections, pyuria and fever. Excretory urogram reveals (A)
delayed visualization of the right kidney at 5 min, (B) some
dilatation of the right collecting system at 15 min. (C)
Posterior Gallium-67 scan reveals diffusely increased
uptake in the right kidney. (D) SemTc DMSA scan reveals
multifocal areas of decreased activity with the RPO pinhole
images showing striated "flares" compatible w i t h acute
pyelonephritis.
disease on the right with several striated "flares"
of decreased activity at the mid and lower pole of
the right kidney, extending from the hilum to the
periphery of the kidney. This patient demonstrates the "hot kidney" on the Gallium-67
citrate study, nonspecific in nature, that may
produce confusion. The patient responded to
antibiotic therapy in a fashion compatible with
acute pyelonephritis.
Figure 3 demonstrates ill-defined increased
Gallium-67 citrate uptake in the left kidney
region of a 2-mo-old female who presented with
fever and a left flank "mass." The high background abdominal activity at 48 hr prevents
differentiating abscess from pyelonephritis or
tumor. Ultrasonic examination demonstrates
enlargement of the kidney without other specific
abnormalities. Excretory urogram shows somewhat diminished visualization of the left kidney
and collecting system. The Technetium-99m glucoheptonate study demonstrates multifocal defects in the mid and lower poles of the left kidney
suggestive of acute pyelonephritis, with overall
diminished uptake compared to the normal right
NUCLEAR RENAL IMAGING
249
79-00-523
2mo. ~
B
Longitudinal
Prone
79-00-523
2mo. ~
79~00-523
2mo.~
LPO
C
kidney. Surgical biopsy and blood cultures confirmed the diagnosis of E. coli pyelonephritis.
Figure 4 demonstrates a striking multifocal
striated "flare" pattern of acute pyelonephritis in
an 8-yr-old male studied with Technetium-99m
DMSA. The child had severe vesicoureteral
reflux, unresponsive to antibiotic treatment; the
Posterior
RPO
Fig. 3.
A 2-mo-old female w i t h f e v e r and left flank
" m a s s . " (A) E x c r e t o r y urogram reveals faint visualization of
t h e left kidney and collecting system. (B) Sonogram demonstrates an enlarged left kidney. (C) Posterior Gallium-67
scan shows ill-defined increased activity in t h e left renal
area, (D) S~mTc glucoheptonate study demonstrates multifocal defects in the inferior and midportion of t h e left kidney.
Biopsy and blood cultures confirmed E. coil pyelonephritis.
patient did not improve and a surgical reimplantation of the ureter was carried out.
Figure 5 demonstrates the serial DMSA scans
documenting the dramatic improvement in the
patient in Fig. 4 resulting in a nearly normal
appearance of the right kidney on the latest
follow-up study. The left-to-right ratio also
HIRSCH HANDMAKER
250
75.00-397
76-00-966
8 cr
99m
Tc-GH
4/3/75
99mTc-DM AS
LPO
Posterior
RPO
Fig. 4. An 8-year-old male with severe right vesicoureteral reflux and recurrent infections. (A) ~=Tc DMSA
images reveal typical " f l a r e " pattern of decreased activity
from the hilum to the periphery, multifocal in nature, on the
right ("hot spots" in the midline of the posterior view are
.....
61517 r
LPO
!POSTERIOR
RPO
10 cm markers).
Fig. 6. A 2-yr-old female with fever and pyuria. Upper
panel shows m"Tc glucoheptonate images that are normal
in posterior parallel hole high resolution view, but show a
discrete defect in the upper pole of the right kidney on RPO
pinhole view. Note the persistent pelvic and ureteral activity at 2 hr on the GHA images. Followup study with DMSA in
the convalescent period (lower panel) confirmed the
response to antibiotics, with no urinary activity seen, and
normal cortical scan.
7/6/76
Fig. 5. Initial, postoperative reimplantation and 3-me
pinhole images (RPOs) in patient described in Fig. 4 demonstrating improvement and return to nearly normal 8emTc
DMSA uptake in kidney following surgery for reflux.
returned to normal and gave little evidence of
residual renal damage from the reflux and pyelonephritis.
Figure 6 demonstrates a right upper pole
defect in acute pyelonephritis in a 2-yr-old
female performed with Technetium-99m glucoheptonate and the normal followup study performed with Technetium-99m DMSA after 2 me
of antibiotic therapy. This complete return to
normal offered good assurance to the referring
physician that the infection was controlled with
no residual disease. Note the ureteral activity
which persists on the Technetium-99m glucoheptonate study 99 min after the injection. It also
should be noted that the defect is clearly seen
only in the right posterior oblique pinhole view.
This is especially true in young patients with
small kidneys.
Figure 7 demonstrates the area of interest
selection for a Technetium-99m DMSA quantitative study for the patient discussed in Fig. 2.
Computer generated left-to-right ratio (1.5/1)
indicated the severity of the disease. (Normal =
0.9-1.1/1)
DISCUSSION
Patients suspected of having acute pyelonephritis rarely demonstrate radiographic findings
either on plain film or excretory urography.
Imaging procedures have not been as helpful in
confirming the presence of acute pyelonephritis
as they have in other disease processes. Conventional radiographic techniques are useful in identifying anomalies of the genitourinary tract that
predispose the patient to infection, such as vesicoureteral reflux, but direct evidence of infection
is uncommon particularly in the early phases of
the disease. In two series, abnormal excretory
urograms were found in only 24% 7 and 28% 8 of
patients with acute pyelonephritis. There is some
disagreement between these two authors, in fact,
regarding the exact nature of the findings: Elkin 9
describes "small volume" pelvis and Silver 8
dilated and distorted pelvicalyceal structures.
Other urographic findings include: (1) renal
enlargement, (2) lowered urine flow and associated delayed pyelogram, (3) diminished concentration of contrast material, (4) nonobstructive dilatation of the ureter, and (5) infrequently,
prolonged or absent visualization of the nephrogram.
NUCLEAR RENAL IMAGING
Fig. 7.
251
A r e a of interest selection and computation of the 2-hr differential renal function in the patient in Fig. 2 (see
Discussion).
Ultrasound examination of the kidneys is
extremely useful in confirming renal or perirenal
abscesses. These are seen as cystic areas of
necrosis in or adjacent to the renal parenchyma;
ultrasound is of little value in confirming acute
pyelonephritis, however. Enlargement of the kidney was the sole abnormal finding in a few
patients in one series/~ Ultrasound can be used to
guide a biopsy needle if histologic or fluid confirmation is required in either pyelonephritis or
other infectious processes.
The use of Gallium-67 citrate in the diagnosis
of acute pyelonephritis was originally proposed
by Kessler et al. t~ Subsequent publications have
verified the reliability of this procedure. 4'12'13
Gallium-67 citrate localizes in polymorphonuclear leukocytes after being cleared from the
blood where it is bound with transferrin. It also
has been documented to localize in areas of high
tissue lactoferrin concentration. ~4 As in other
sites of bacterial infection, therefore, increased
gallium uptake can be expected in bacterial
infections within the kidney. The accuracy of
86% in distinguishing upper tract from lower
tract infection at 48 hr reported by the Kessler
group in a later paper J5 compares favorably with
the more invasive, traditional confirmatory studies for acute pyelonephritis, including ureteral
catherization and bladder-washout. Difficulty
with the Gallium-67 citrate study arises from the
inability to distinguish intrarenal from extrarenal (i.e., perinephric) infectious processes, and
the normal concentration of the radiopharmaceutical by the kidneys. 16'17 A variety of other
diseases involving the kidneys, including acute
tubular necrosis and vasculitis have also been
reported to produce increased renal gallium concentration.~8
Renal cortical radiopharmaceutical agents
were first suggested as potentially useful in
detecting acute pyelonephritis by Davies. ~9 The
advantages of using Technetium-99m cortical
agents include highest resolution images for
detection of parenchymal abnormalities, ready
availability of the radiopharmaceuticals, and the
capability for simultaneous quantitative evaluation of renal function in acute and posttreatment
follow-up periods. Either of the commonly used
renal cortical radiopharmaceuticals, Technetium-99m glucoheptonate 2~ or Technetium99m DMSA is acceptable, though the latter
remains unapproved by the FDA some 8 yr after
its appearance in the literature. 5'22 DMSA is the
preferred material for renal cortical imaging as
no confusing urinary excretion is encountered in
the pelvicalyceal structures 2 hr after injection,
even in patients with obstructed or dilated collecting systemsd Our experience with cortical
agents suggests that on occasion a specific pattern is seen which may be typical for acute
pyelonephritis. The striking striated or "flare" of
decreased renal activity, often multifocal in
nature, radiating from the pelvicalyceal structures toward the periphery of the cortex has been
seen in several patients with acute pyelonephritis. (Figs. 1, 2, and 4) This corresponds to the
angiographic and pathologic findings of peritubular edema, increased interstitial pressure and
plugs of cellular debris within the tubules characteristic of acute pyelonephritisfl3'24 Other scintigraphic findings, such as diminished overall
function or focal cortical defects in the presence
252
HIRSCH HANDMAKER
of a normal IVP and ultrasound examination
increase the probability of acute pyelonephritis.
The synergistic use of a combination of these
procedures including the cortical scan, Gallium67 citrate or Indium-1 11 white blood cell scan,
ultrasound and/or urography should permit a
higher degree of specificity for the diagnosis of
acute pyelonephritisY '26
No patient in our series with proven acute
pyelonephritis had a normal renal cortical scan.
For this reason, and its convenient 2-hr completion time, we prefer to perform this imaging
procedure first. If an abnormal study, nonspecific in nature, results from the renal cortical
scan, in association with the ultrasound finding
of a cystic mass in or adjacent to the renal
parenchyma, Gallium-67 or Indium-111 WBCs
may be used to further characterize the abnormality as pyogenic or nonpyogenic. When the
gallium or WBC scan has been performed first,
as in patients with fever and no localizing signs or
symptoms, it may be necessary to further characterize abnormalities as renal or extrarenal in
nature with a renal cortical scan. This wilt assist
in determining whether the "hot kidney" is due
to pyelonephritis or perinephric abscess.
Following our initial experience with Technetium-99m DMSA in renal cortical imaging, it
seemed logical that its similarities to the organomercurials would permit its substitution in this
technique for assessing differential renal function. 27 Using a modification of Raynaud's Mercury-197 "fixation" technique, 28 we presented
and published our clinical results and concluded
that D M S A was a satisfactory agent for this
purpose. 29 Subsequently, in vitro animal and
human confirmation have been published by
several authors. 3~ Either simple left-to-right
ratios or more elaborate differential kidney
uptakes may be performed from 2 to 24 hr after
injection of the material. While it is not the
purpose of this report to describe the quantitative
techniques, they are useful additions to the renal
cortical scan in assessing the degree of renal
impairment produced by acute pyelonephritis.
The second part of this two issue series has a
detailed review of current approaches to quantitative imaging. They can be readily performed at
the time of the initial imaging and add no
additional radiation exposure or invasiveness to
the procedure. The ability to determine and
monitor the return of function in the involved
kidney following medical or surgical treatment in
a convenient manner is a significant factor favoring the use of D M S A in these patients (Fig. 5).
Indium-1 1 l-labeled autologous leukocytes
have been found useful in this disease entity. This
technique appears to be superior to Gallium-67
citrate imaging in that the radiopharmaceutical
is not normally excreted by the kidneys; renal
uptake of any intensity, therefore, will be indicative of inflammatory disease. 6 Greater experience with this radiopharmaceutical will be necessary to ascertain its exact role in the evaluation of
patients suspected of having acute pyelonephritis.
The techniques described should aid in the
prompt and accurate diagnosis of acute pyelonephritis where it is clinically in question.
Renal cortical imaging should clarify the confusion that often surrounds patients with nonspecific imaging results such as enlarged kidneys
on ultrasound, "hot kidneys" on gallium scan
and clinical symptoms of infection. It should not
be necessary to postulate the existence of an
entity such as "acute lobar nephronia" in
patients with bacterial infection of the renal
parenchyma, nor to perform angiography) 3 The
patient in Fig. 3 fulfilled all the "criteria" for
A L N , and, as might be expected, had typical
biopsy and bacteriologic evidence of acute pyelonephritis.
ACKNOWLEDGMENT
The author wishes to express his thanks and appreciation
to RoseAnn Anderson and Carol Lewis for their diligence
and technical skill, to Bradford Young and Raymond Fay for
their cooperation and advice, and Pete Peterson for his
tenacity in completing the preparation of this manuscript.
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NUCLEAR RENAL IMAGING
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