Download Transplanted Kidney Function Evaluation

Transplanted Kidney Function Evaluation
Ays-e Aktas-, MD*
The best option for the treatment of end-stage renal disease is kidney transplantation. Prompt
diagnosis and management of early posttransplantation complications is of utmost importance
for graft survival. Biochemical markers, allograft biopsies, and imaging modalities are used for
the timely recognition and management of graft dysfunction. Among several other factors,
improvements in imaging modalities have been regarded as one of the factors contributing to
increased short-term graft survival. Each imaging procedure has its own unique contribution to
the evaluation of renal transplant dysfunction. In the era of multimodality imaging and emerging
clinical considerations for the improvement of graft survival, evaluating an imaging modality in
its own right may not be relevant and may fall short of expectation. Recognized as being mainly
a functional imaging procedure, radionuclide imaging provides valuable information on renal
function that cannot be obtained with other imaging modalities. For evaluating and establishing
the current place, indications, and potential applications of radionuclide renal transplant
imaging, a classification of renal allograft complications based on renal allograft dysfunction is
essential. The major factor affecting long-term graft loss is chronic allograft nephropathy. Its
association with early posttransplantation delayed graft function and repeated acute rejection
episodes is well documented. Long-term graft survival rate have not improve significantly over
the years. Imaging procedures are most commonly performed during the early period after
transplantation. There seems to be a need for performing more frequent late posttransplantation imaging for the evaluation of acute allograft dysfunction, subclinical pathology, and
chronic allograft changes; for understanding their contribution to patient management; and for
identification of pathophysiological mechanisms leading to proteinuria and hypertension. With
its unique advantage of relating perfusion to function, the potential for radionuclide imaging to
replace late protocol biopsies needs to be investigated.
Semin Nucl Med 44:129-145 C 2014 Elsevier Inc. All rights reserved.
E
nd-stage renal disease is a cause of significant morbidity
and mortality, with a worldwide increase in its incidence
and prevalence. Renal replacement therapy with hemodialysis
or peritoneal dialysis and transplantation of a graft from a
deceased or living donor constitute the major treatment
options in this patient group. Owing to persistent organ
shortage and increased demand, the use of marginal kidneys
from expanded criteria donor (ECD) and cardiac death donors
has increased. Renal transplantation is the best choice of
treatment as it is associated with better survival rates, improved
quality of life, and lower costs. However, implantation of a
renal graft does not mean an uneventful course. Renal transplant complications can be observed during the early posttransplantation period and on follow-up, resulting in graft
Faculty of Medicine, Department of Nuclear Medicine, Bas-kent University,
Ankara, Turkey.
*Address reprint requests to Ays-e Aktas-, Fevzi Çak. Cad., 10. sk. No:45,
Bahçelievler, Ankara 06480, Turkey. E-mail: [email protected]
0001-2998/14/$-see front matter & 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1053/j.semnuclmed.2013.10.005
dysfunction and in severe cases graft loss, necessitating
hemodialysis or the use of a new transplant.
Despite the survival benefit conferred by transplantation,
renal allograft recipients still have a high mortality rate
compared with population controls. Posttransplantation survival rates vary depending on patient-related factors, such as
age, gender, race, and presence of comorbid conditions; source
of the allograft; operation-related factors; degree of immunosuppression; and postoperative complications. During the
early posttransplantation period, the immune system is
routinely suppressed to minimize the incidence of graft
rejection. The graft failure rate has significantly decreased over
the years because of improved surgical technique, better
immunosuppressive therapy, and better monitoring techniques. Although short-term survival rate at 1 year after
operation has improved over the past 2 decades, long-term
failure rate at 5 years or more did not change significantly.1-3
There are conflicting results in the literature about the
influence of potential risk factors on long-term graft survival.
The only factor shown to have a certain influence on the
129
A. Aktas-
130
outcome is the source of the graft. Survival rate at 5 years was
reported to be 90% for living related, 83% for non-ECD, and
69% for ECD deceased donor grafts.1
Owing to the importance of renal transplantation in patient
management and limited availability of donor kidneys, detailed
evaluation of factors that affect transplant survival is essential.
Noninvasive imaging modalities have become an important
part of transplantation programs for evaluating early posttransplantation vasculature and function, differential diagnosis
of early allograft dysfunction, and evaluating long-term transplant complications and as a prognostic tool for short- and
long-term graft survival.
Renal Transplant Complications
There are various schemes used for the classification of renal
transplant complications. The most commonly used ones
either classify them as surgical vs medical or, depending on
the localization of the underlying etiology, as prerenal, renal,
and postrenal. Surgical complications comprise fluid collections, urinary obstruction, and vascular complications. Medical
complications are related to parenchymal pathologies as
acute tubular necrosis (ATN), acute rejection (AR), and drug
toxicity.
From the renal function point of view, renal allograft
dysfunction can be in the form of primary nonfunction or
most commonly delayed graft function (DGF) during the early
period after transplantation. DGF is characterized with a failure
of renal function tests to improve early posttransplantation. At
other times, allograft dysfunction is generally diagnosed based
on an acute or slow deterioration of renal function, as reflected
by rising serum creatinine levels, proteinuria, hypertension, or
abdominal pain. From the functional point of view, a
classification scheme for the most common etiologic factors
of renal transplant dysfunction is summarized in Table 1.
Evaluation of Renal Transplant
Complications
Nonimaging Procedures
Renal Function Tests
Renal transplant function is commonly monitored using serum
creatinine level. Its production is dependent on age, gender,
and muscle mass. Serum creatinine concentrations may remain
within the reference range until approximately half of renal
function has been lost. Plasma cystatin C level, 24-hour urinary
output, and 24-hour creatinine clearance are among the
measures used for the evaluation of renal function in transplant
recipients. Creatinine reduction ratio and 24-hour urine
creatinine excretion from posttransplant days 1-2 are shown
to be effective measures of evaluating renal transplant status
and for predicting graft survival.4
Allograft Biopsy
Percutaneous renal needle core biopsy is performed
mainly in the setting of acute graft dysfunction and is
Table 1 Classification of Renal Transplant Complications Based
on the Time and the Course of Renal Transplant Dysfunction
After Transplantation
1. Delayed graft function (DGF)
A. Due to ischemia-reperfusion injury
a. Acute tubular necrosis
B.
Nonischemic causes of DGF
a. Acute rejection
b. Drug toxicity
c. Vascular complications
d. Urinary complications
i. Obstruction
ii. Urinary leak
iii. Urinary bladder dysfunction
e.
Peritransplant fluid collections
2. Acute renal allograft dysfunction
A. Acute rejection
B. Urinary tract infection
C. Obstruction
D. Tubulointerstitial nephritis
3. Slowly deteriorating graft function
A. Chronic allograft nephropathy
B. Drug toxicity
C. Renal artery stenosis
D. Transplant glomerulopathy
E. Infections (particulary viral infection due to
cytomegalovirus)
the gold standard to establish the correct diagnosis. However, regardless of renal function, biopsies can also be
obtained at predetermined times after renal transplantation, and these are called protocol biopsies.5 The rationale
behind the protocol biopsies is the potential benefit of
early recognition of allograft pathologies, thus their earlier
treatment resulting in a better long-term outcome. However, there is debate over the performance of protocol
biopsies and conflicting results concerning its possible
benefits.6 Banff classification has set the widely accepted
criteria for the diagnosis of renal allograft pathologies.7
Nonradionuclide Imaging Procedures
Renal transplant imaging is most commonly performed during
the first 7-12 days after transplantation. Imaging procedures
are used as necessary during follow-up based on renal function
tests and clinical symptoms. Ultrasonography (US), radionuclide imaging, CT, and MRI are the main imaging procedures used in the evaluation of renal transplant status.
US with color Doppler imaging is the first-line imaging
during the early posttransplantation period. This modality not
only provides vascular flow information and define perirenal
fluid collections but also establishes a baseline for future
comparisons. It is also useful for guiding renal biopsy and
drainage of large fluid collections. Limitations include relatively
Transplanted kidney function evaluation
poor anatomical detail, operator dependence, and lack of
functional assessment.
CT is rarely used in the evaluation of renal transplants. The
concern over the exposure to ionizing radiation in a patient
under lifelong immunosuppression and the use of nephrotoxic
contrast agents limit the use of CT in this patient group.
However, CT-guided aspiration and drainage procedures may
obviate the need for surgical interventions.
MRI is a relatively newer imaging approach used in renal
transplant monitoring. It has the ability to evaluate renal
transplant structure, including the surrounding tissues, the
blood vessels, and the urinary tract. New advances in MRI
technology have led to the emergence of MR nephrourography, which provides both anatomical and functional evaluations of the kidney in a single examination. However, some
transplantation centers avoid MRI in renal transplant recipients
owing to the concern over systemic nephrogenic fibrosis
attributed to the use of contrast media, particularly the
gadolinium-based salts.
131
been increased by modern techniques such as tissue pulsatility
index, maximal fractional area determination, and contrastenhanced US. Though these methods are not used to evaluate
renal function directly, they are suggested to have a higher
potential for differentiating parenchymal complications.
Radionuclide Imaging
Renal scintigraphy is a valuable approach to assess the
3 sequential phases of renal function. The first phase consists
of the rapid dynamic imaging that is done during the first
minute after tracer injection. This evaluates perfusion. The
second phase is the period in which the nephrons extract the
tracer from the blood and excrete it by glomerular filtration or
tubular secretion or both. The third phase is the period during
which the tracer drains through the pelvicalyceal system. The
sequential changes that occur can be demonstrated with the
use of both tubular and glomerular agents.
Radiotracers
The Current Use of Imaging Procedures in
Renal Transplant Perfusion and Function
Renal Perfusion
Renal perfusion impairment can result from various pathologies. These may involve the main renal artery, vein and its
branches, or renal microcirculation. Renal artery thrombosis,
renal vein thrombosis, and renal artery stenosis (RAS) constitute the major primary vascular pathologies affecting the
transplanted kidney. Primary vascular pathologies are seen in
less than 10% of the recipients. Renal parenchymal pathologies
lead to hemodynamic alterations, resulting in an increased
resistance in renal vasculature. A major part of renal vascular
imaging is related to evaluation of perfusion owing to these
hemodynamic consequences. Changes in renal vascular resistance can be observed early or late in the course of a
parenchymal pathology depending on the etiology. Renal
perfusion imaging can be performed by radionuclide angiography or various forms of US, such as spectral, color, and
power Doppler sonography. Intrarenal measurement of indices like resistive index (RI) and pulsatility index is an indirect
measure of renal parenchymal pathology, whereas measurement of specific parameters from renal artery and its branches
may as well be a reflection of primary vascular pathology.
Likewise, renal perfusion impairment detected on radionuclide
imaging is for the most part a reflection of hemodynamic
alterations due to renal parenchymal pathologies.
Renal Function
For years, radionuclide renal imaging has been the only
imaging procedure to determine the functional status of the
transplanted kidney. With this method, renal perfusion,
physiological measures of renal function, and drainage through
the urinary tract can be evaluated. Functional information
similar to that provided by radionuclide imaging was attributed
to MR nephrourography, suggesting that this modality is able
to yield a full range of the causes of renal transplant
dysfunction. During recent years, diagnostic power of US has
Technetium 99m-labeled tubular or glomerular agents are
used for renal transplant evaluation. The principal glomerular
agent used for dynamic imaging of the kidney is diethylenetriaminepentaacetic acid (DTPA). The renal extraction fraction
of DTPA, that is the percentage of the agent extracted with each
pass through the kidney, is 20%. Though a small fraction of
DTPA may be bound to protein, this is not a problem in clinical
applications of glomerular filtration rate (GFR) measurements.
Currently used tubular agents are mercaptoacetyltriglycine
(MAG3) and ethylene cysteine. MAG3 is highly protein bound
and is cleared mainly by the proximal renal tubules. Its renal
extraction fraction is 40%-50%, more than twice of DTPA. The
clearance rate of MAG3 is an independent measure of effective
renal plasma flow (ERPF) and renal function. As MAG3 is
more highly protein bound than DTPA, general blood pool
activity and that present in the liver are more prominent on the
early images, especially in patients with impaired renal
function. Furthermore, a small portion of MAG3 accumulates
in the gall bladder within 30-60 minutes of injection. The gall
bladder activity can simulate pelvic or calyceal activity on
delayed images. Because of their higher extraction and rapid
plasma clearance, tubular agents can provide better kidneybackground ratio and are generally preferred in cases of
impaired renal function.
As the extraction of tubular agents by the kidney is higher
than that of DTPA, lower doses can be administered. Doses in
the ranges of 1.5-8 mCi for tubular and 8-10 mCi for
glomerular agents would be sufficient. Oral hydration of the
patient is encouraged 30 minutes before imaging. Patients
should drink 10 mL/kg of liquid. If oral hydration is contraindicated, intravenous hydration with normal saline or dextrose saline, 100-500 mL, is given 30 minutes before imaging.
Acquisition
The gamma camera is positioned over the kidney in the iliac
fossa. The lower abdominal aorta and the external iliac artery
should be in the field of view. A good bolus injection is
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mandatory for the accurate evaluation of renal transplant
perfusion. The vein chosen for radiopharmaceutical administration should be as large as possible. A large-field-of-view
camera with low-energy all-purpose collimator should be
used. The study can be acquired in 64 64 or 128 128
matrix.
The images should be acquired every 1 second or faster for
the first 40-60 seconds and then 10-30 second per frame for
20-30 minutes. The fast imaging during the first minute is for
perfusion evaluation, and serial images of longer duration are
for evaluating extraction and drainage patterns. Preinjection
and postinjection syringe images and imaging of the injection
site are necessary for accurate quantification of renal function.
Postvoiding static images taken after the completion of the
study can serve to assess the nature of peritransplant fluid
collections, obstruction, and reflux.
Evaluation of Renal Perfusion and Function
With Radionuclide İmaging
Renal Perfusion
Renal perfusion imaging is defined as the rapid dynamic renal
examination carried out in the first minute after the administration of radiopharmaceutical. Radionuclide angiography
and first-pass evaluation are synonymous words. For a
thorough evaluation of perfusion, the renal and arterial (aortic
or iliac) flow curves are generated by placing regions of interest
(ROIs) over the graft and artery. With a proper bolus injection,
a peak-plateau pattern (upslope first followed by a downslope
reaching to a plateau) is observed on the arterial curve using
both glomerular and tubular agents. The arterial curve is used
to ascertain that a proper bolus injection has been given. The
half time of the downslope should be less than 10 seconds.8
The subsequent portion of the perfusion curve after the
initial rise can be termed as second-phase perfusion curve.
With DTPA, it is usually descending, resulting in a peakplateau pattern similar to arterial curve. However, with MAG3,
this portion is usually ascending. This dissociation was thought
to be owing to the differences in the percentage extraction of
glomerular and tubular agents.9,10
Quantitative Perfusion Parameters. Several methods of
quantifying perfusion have been proposed.
1. Kirchner's kidney-aorta ratio (K/A): This is the first ratio
used to quantitate renal perfusion. It is the ratio of the
slope of the ascending portions of the renal and arterial
curves. The normal range is 0.64-1.16. Kirchner et al,11
using Tc-99m DTPA, have reported that K/A correlated
well with clinical and pathologic assessments of renal
function. In another study, K/A, as measured by Tc-99m
MAG3, was found to be similar to those previously
obtained with Tc-99m DTPA.12
2. Hilson's perfusion index (PI): This is the ratio of the area
under the arterial curve to peak divided by the area
under the renal curve to peak. This parameter was
suggested to clearly differentiate normal grafts and those
with impaired renal function, especially the rejection
A. Aktascases.13 In subsequent studies performed in renal transplant recipients, differential diagnostic power of PI and
its alteration on serial scans was reported to be low.14,15
One modification of this method is to use only
cortical ROI.
3. Parameters that measure the rate of vascular transit are as
follows:
a. time to peak in seconds on the graft perfusion curve,
b. washout time—time in seconds for declining counts
on the renal perfusion curve to reach one half of the
peak value,
c. time in seconds between the peaks of the iliac and
graft curves (ΔP), and
d. peak to plateau ratio (P:PL)—peak perfusion count
divided by plateau count on the renal perfusion curve.
All these parameters require a high-quality bolus injection
for reliable results. Calculating renal vascular transit time by
deconvolution analysis and assessing true renal blood volume
as a percentage of cardiac output have been suggested.16-18
These methods require multiple curve analysis, and their
advantage over simpler methods has not been validated.
Renal Extraction and Excretion
Time-activity curves generated using a ROI over the kidney
reflect sequential changes in renal function. Each such curve
is called a renogram. Radionuclide renograms provide a
method of quantitatively evaluating kidney function. Background subtraction is recommended for generating renogram
curves using elliptical, perirenal, subrenal, or contralateral
mirror ROI. All Tc-99m-labeled agents exhibit a similar
renogram pattern, with a vascular peak followed by extraction
peak and decline of activity. As the extraction of tubular agents
is higher than that of glomerular agents, extraction phase is
steeper with tubular agents. The parenchymal function of the
transplanted kidney can be evaluated by visual inspection of
the acquired images and renogram curves or by calculating
quantitative parameters from renogram data or a combination
of data derived from renogram curve, bladder curve, plasma
samples, and urine collection.
Quantitative parameters derived from backgroundsubtracted renogram curves are easy to determine, can be
obtained using both tubular and glomerular agents, and do not
require blood sampling. Commonly used quantitative parameters include time to peak of the renogram (Tmax), half time of
the elimination phase (T1/2), and percentage of the peak
activity retained at 20 minutes (R20). For DTPA, the ratio of
peak perfusion to peak uptake (P:U) was suggested to establish
a relation between perfusion and uptake. This ratio, together
with P:PL, was used to classify DTPA renogram patterns.10
Using tubular agents, the slope of the ascending portion of
the curve after the perfusion peak was calculated and is
frequently termed as tubular function slope (TFS). This slope
was thought to represent the active extraction of the radiopharmaceutical by epithelial cells of the proximal renal
tubules.19 The uptake capacity within the first 10 minutes
that reflects graft perfusion and function because of tracer
uptake and retention has also been used.20 MAG3 renogram
Transplanted kidney function evaluation
curve patterns were graded for the evaluation of early postoperative graft dysfunction and prediction of graft survival.21
Physiological measures of renal function, like GFR, using
glomerular agents and renal plasma flow (RPF) using tubular
agents can be obtained by gamma camera methods available as
part of the software packages or by using plasma clearance
methods with single or multiple blood sampling. RPF equals
the clearance of a substance if it is taken up exclusively by the
kidney with an extraction efficiency of 100%. Owing to the
incomplete extraction of MAG3, RPF was modified to ERPF.
Among the plasma clearance techniques, the simplified singlesample methods are recommended.
Renal transit time measurements with or without using
deconvolution analysis were suggested. Parameters like Tmax,
T1/2, and R20 can be regarded as simple measures of renal
transit time. Deconvolution analysis that calculates renal
vascular transit time and mean transit time is a timeconsuming process, and its clinical utility in differentiating
allograft pathologies remains controversial. Simple indices of
transit time have proven to be diagnostically comparable to
more complicated deconvolution methods.22
Indications of Radionuclide İmaging in Renal
Transplant Evaluation
Over the years, radionuclide renal imaging use during the early
posttransplantation period has decreased. In the past, most
centers were performing renal studies once or twice within the
first week after transplantation. Recent algorithms are generally
based on the use of sonography and biopsy. However, there
are still centers routinely performing renal studies especially
during the early posttransplantation period. Most renal transplant patients are discharged from the hospital within 7-12
days after operation. Imaging performed before the initial
postoperative discharge can be regarded as early evaluation,
whereas any imaging performed at a time after the postoperative stabilization of function can be regarded as late
evaluation. Indications of renal scintigraphy during the early
and late periods after transplantation have been summarized
in Table 2.
Early Postoperative Graft Function Evaluation
Baseline Function Determination. The purpose of radionuclide studies performed during the early period after
transplantation is to serve as a diagnostic aid in the
immediate postoperative management and to provide
baseline study for future comparisons. It was initially
suggested that early posttransplantation complications could
more specifically detected by performing serial scans that
demonstrate changes in renal function. In a study performed
with MAG3, the diagnostic specificity of serial scans was
accepted to be insufficient for the differential diagnosis of
common early posttransplantation complications, and it was
suggested to be performed only in primary nonfunctioning
grafts.21 In several studies performed with DTPA, serial
evaluation of perfusion and function parameters was
reported to be effective for the diagnosis or differential
diagnosis
of
common
early
posttransplantation
133
Table 2 Indications of Renal Scintigraphy in Renal Transplant
Evaluation
1. Early after the operation
A. Baseline function determination
i. Diagnostic information for early postoperative
management
ii. Baseline data for follow-up monitorization
iii. Prognostic information
B.
C.
D.
E.
Evaluation of delayed graft function
Differentiation of parenchymal causes of graft
dysfunction
Evaluation of peritransplant fluid collections such as
urinary leaks, lymphocele, and hematoma
Evaluation of vascular complications
2. Late after the operation
A. Evaluation of acute renal allograft dysfunction
B. Evaluation of subclinical pathology
C. Evaluation of slowly deteriorating graft function
D. Evaluation of suspected renal artery stenosis
complications.23-25 In the current posttransplantation imaging programs, most centers perform renal scintigraphy only in
cases of DGF. In some centers, routinely performed twiceweekly posttransplantation renal scanning programs are
replaced by a single study before initial discharge in uncomplicated cases.
In addition to their diagnostic and monitoring contribution,
baseline scans were shown to have an association with shortand long-term prognoses. Short-term renal transplant survival
rates have significantly improved during the past 2 decades
since the introduction of new-generation immunosuppressive
agents. Currently, the focus of research has shifted to the
assessment of graft survival at 5 years or more after transplantation. Several biochemical, histologic, immunologic,
imaging, and composite markers have been proposed to bear
prognostic information. Serum creatinine level obtained at
1 week or 12-month after transplantation and creatinine
reduction ratio on the second posttransplant day have been
proposed as reliable predictors of long-term survival.26-28
Several perfusion and nonperfusion parameters with either
tubular or glomerular agents were investigated for this
purpose. One study has shown that using tubular agents,
single-sample ERPF measured in the immediate posttransplant
period and renogram parameters such as Tmax and R20 to be
significant predictors of survival for cadaver transplants, but
not for living related donor transplants.29 Guignard et al30
included only grafts with delayed function and found a
significant correlation between 72-hour postoperative MAG3
scan findings and transplant success at 1 year. They found K/A
to be a better parameter for short-term graft prognosis
compared with PI. In a study that classified early postoperative
MAG3 renogram curves, both short- and long-term prognoses
were reported to be poor with a renogram grade 2 or more.21
Higher renography grades were associated with a longer time
to onset of graft function, long duration of cold ischemia time,
134
cadaver donation, and high donor and recipient ages. In
another study using MAG3, a strong relationship was found
between day 3 PI and serial creatinine levels at 1, 3, and 12
months after transplantation.28 In another study, a parameter
derived from MAG3 renogram that reflected both perfusion
and function of the graft was shown to correlate with long-term
graft survival.20 Gupta et al31 evaluated 290 DTPA studies
obtained at days 1 and 4 after transplantation for the assessment of short- and long-term prognoses. They found that
among various scintigraphy parameters, only PI had consistent
association with both short- and long-term prognoses. The
association of long-term prognosis with scintigraphic perfusion
parameters was better for deceased donor grafts. For recipients
of live donor grafts, nonscintigraphic parameters such as serum
creatinine or GFR provided better correlation.
Evaluation of DGF. DGF caused by failure of the transplanted
kidney to function properly after transplantation has been
associated with longer in-hospital stays, reduced graft or patient
survival, and increased incidence of AR episodes.32,33 DGF
mainly occurs in patients with deceased donor transplantation
and has a lower incidence in living donor recipients. The older
method of identifying DGF, the requirement for dialysis in the
first week after transplantation, was not standardized and was
subjective, as the threshold criteria for dialysis vary among
institutions. In recent years, instead of dialysis requirement,
DGF is identified based on serial serum creatinine levels and
rate of reduction in serum creatinine.4,34 According to these
criteria, reported rates of DGF range between 4% and 50%,
with the living donors having a much lower rate.33,35
A review of the literature reveals that there is no welldemarcated definition for DGF. A strict criterion recently
proposed by Yarlagadda et al33 for the identification of DGF
is “a combination of dialysis need (preferably more than once)
or creatinine reduction ratio of less than 25% or lower within
the first 48h post-transplant.” A comprehensive definition for
DGF suggested in the same study was “the failure of the
transplanted kidney to function properly in the early phase
after transplantation due to ischemia-reperfusion and immunological injury.” In some clinical studies, ATN, AR, and drug
toxicity were regarded as etiologic factors for DGF. Yarlagadda
et al33 have proposed DGF to be present only after eliminating
causes of early graft dysfunction that are not related to
ischemia-reperfusion injury. These authors emphasized the
importance of early diagnosis of DGF and the necessity of
initiating therapy within hours of ischemia-reperfusion injury.
Because of conflicting definitions regarding DGF, there are
imaging studies performed during the early posttransplantation period that evaluated DGF either by excluding patients
with AR or by evaluating postoperative causes of DGF with the
aim of differentiating ATN and AR. The main pathologic
finding related to DGF is ATN. During the early period after
transplantation, ATN, AR, and drug toxicity are the most
common causes of graft dysfunction, and combined presence
of these factors might potentiate DGF.
ATN is the most common cause of DGF during the early
posttransplantation period. It is more common in cadaveric
than in live donor transplants. ATN represents necrosis of
A. Aktastubular cells that commonly slough off into the tubular lumen
and secondarily cause obstruction leading to oliguria. It is
principally related to the process of ischemic injury to the
transplanted kidney. In addition, reperfusion may lead to
oxygen free radical injury. It usually occurs right after the
operation and resolves within 2 weeks, depending on the
degree of ischemic insult. In patients with prolonged or
markedly DGF, the consideration of ATN is based on biopsy
in combination with exclusion of other causes.
With radionuclide imaging, relatively preserved perfusion
as compared with clearance has been suggested to indicate
ATN. However, renogram pattern is different for glomerular
and tubular agents. With tubular agents such as MAG3, the
renogram curve is slightly accumulative. There is a delay in
transit with delayed time to maximal activity. On sequential
images, marked parenchymal retention is seen. With glomerular agents, there is a descending renogram curve without a
peak activity. In most cases, no activity in bladder could be
detected and there is also a slight progressive increase in
background activity. The discrepancy in renogram pattern
between glomerular and tubular agents can be explained by
different handling of radiopharmaceutical in necrotic tubular
cells and tubular lumen. Ischemic damage is known to increase
the permeability of the tubular basement membrane, allowing
molecules that are filtered to diffuse back into the vascular
compartment.36 In case of glomerular agents, more radioactive
material reaches to tubular lumen that is to be absorbed to
vascular compartment. With tubular agents, there is progressive accumulation in necrotic tubular cells. The findings of
DTPA and MAG3 in a patient with ATN are represented in
Figure 1.
El-Maghraby et al19 studied patients with DGF using TFS
derived from serial MAG3 scans. This study revealed only the
cold ischemia time to be an independent risk factor for a low
TFS. Most renal transplant patients experienced a recovery
phase from postischemic injury, but grafts from marginal
donors were more likely to experience DGF. It was suggested
that after the initial recovery from postischemic injury, the TFS
may be used as a marker for functional renal mass. In another
early posttransplantation study performed with serial MAG3
scans, recipients of cardiac death donors were selected and a
tubular extraction parameter was used to monitor the
changes.37 A significant correlation was observed between
tubular extraction rate and dialysis dependence. Effective renal
plasma calculated from a single blood sample following a
MAG3 scan was shown to identify patients at high risk of
developing DGF.38
Differentiation of Parenchymal Causes of Graft Dysfunction. AR may occur at any time after the first few days
to years after the transplantation. Because of the advances
in immunosuppression, its incidence has significantly
decreased over the years. If promptly recognized, it is
normally reversed by high-dose steroids or antibody
therapy. Percutaneous core needle biopsy is the gold
standard for its diagnosis. In Banff classification,
tubulitis and intimal arteritis are regarded as the
principal lesions indicative of AR. ARs of Banff grades
Transplanted kidney function evaluation
135
Figure 1 (A and B) Tc-99m DTPA images and renogram curve in a patient with early posttransplantation ATN. There is a
descending pattern on renogram curve with no graft peak; (C and D) Tc-99m MAG3 images and renogram curve in the
patient taken 1 day after DTPA study. There is an accumulative pattern on renogram curve. (Color version of figure is
available online.)
I and IIA show features of mild-moderate interstitial
infiltration and tubulitis. Vascular involvement starts
with grade IIB and is most severe in grade III. Despite
the distinct histologic presentations, previous studies have
shown that grades I and II AR seem to have similar clinical
behavior, rejection response rates, and graft survival after
reversal of the attack.39
In the report of radionuclides for the evaluation of the
transplanted kidney, it was stated that cell-mediated AR and
ATN have similar scan appearances with MAG3, and that
these entities can be separated by their time course and
sequential perfusion and function changes, provided an
early posttransplantation study is available.40 Accordingly,
on serial studies, the graft function declines in AR and
improves in uncomplicated ATN. Renogram curves were
graded according to uptake or excretion pattern by using
hippurane renography.8 A decrease in renal uptake of a full
grade or more combined with a loss of uptake peak on the
graft histogram was reported to be coincident with rejection
after the first postoperative days. Similar changes immediately after transplantation were regarded to be owing to the
combination of ischemia and cyclosporine A nephrotoxicity. Lin and Alavi9 evaluated the slope of the second phase
of MAG3 perfusion curve. Patients with graft dysfunction
had either ascending, flat, or descending pattern with the
most (66.1%) having an ascending curve. They found a flat
or descending second-phase perfusion curve to be highly
predictive of graft dysfunction.
There are also studies performed with DTPA that evaluated
acute renal transplant rejection. Bellomo et al41 investigated the
utility of serial Tc-99m DTPA renal images for diagnosing AR
in patients taking cyclosporine. They found that even in
cyclosporine-treated patients, Tc-99m DTPA renal scintigraphy was of clinical value with a specificity of 87.9% for the
diagnosis of AR. Jackson et al42 evaluated renal washout
parameter from the perfusion curve of DTPA. They found a
washout value more than 28 second to be consistent with
histologically diagnosed rejection, and this parameter appeared
136
to change rapidly in parallel with clinical status. In one study,
DTPA scan was found to be both sensitive and specific for the
diagnosis of AR in the absence of ATN.23 In another study,
functional perfusion images were used to evaluate global
transplant perfusion. With this method, ATN and cellular
rejection could not be distinguished but both could be
differentiated from vascular rejection.43
Drug Toxicity. Calcineurin inhibitors like cyclosporine
and tacrolimus can be nephrotoxic by causing afferent
ateriolar vasoconstriction and tubulointerstitial injury.
Earlier
posttransplantation
radionuclide
studies
performed under cyclosporine use revealed conflicting
results. In patients taking cyclosporine, DTPA was found
to be still effective in the diagnosis of AR and drug
toxicity.41,44 In another study performed under
immunosuppression with cyclosporine, limited value
for DTPA was reported in the management of allograft
dysfunction.15 Currently, different drug combinations
are used for immunosuppression, and the overall AR rate
within 1 year after transplantation was reported to be less
than 15%.45 The concern over subclinical rejection or
borderline rejection and their long-term effect on graft
survival had led transplant surgeons to start antibody
induction therapy and modify their maintenance
immunosuppressive regimens.5
Evaluation of Peritransplant Fluid Collections. In the early
posttransplantation period, fluid collections around the kidney
are seen in up to 50% of cases. Common peritransplant fluid
collections include hematoma, seroma, urinoma, lymphocele,
and abscess. US is the method chosen for evaluating
peritransplant fluid collections.
Urinary leaks are usually seen within the first 2 weeks and
occur in approximately 6% of cases. They present with pain,
swelling, and discharge from the anastomosis site. Extravasation may originate from the renal pelvis, ureter, or ureteroneocystostomy site. Radionuclide renal studies show
progressive intense accumulation of activity.46 Another frequent cause of peritransplant fluid collection is lymphocele
formation. Kumar et al47 studied scintigraphic patterns of
lymphocele using DTPA. An initial photopenic area with or
without a surrounding rim of increased tracer activity that filled
up with tracer on delayed images was the most frequent
pattern. Persistent photopenic area was a less common
presentation. Other fluid collections such as seroma or
hematoma formations appear as persistent photopenic defects
around the kidney.
Evaluation of Vascular Complications. Renal artery
thrombosis and renal vein thrombosis or stenosis are among
uncommon but serious early complications. With
radionuclide imaging, total photon-deficient area in renal
artery thrombosis and a pattern similar to ATN in renal vein
thrombosis were reported.48
A. AktasLate Postoperative Graft Function Evaluation
Evaluation of Acute Renal Allograft Dysfunction. Acute renal
allograft dysfunction is defined as a 25% or greater increase in
serum creatinine level at any time after the operation following
a period of stable graft function. In fact, most AR episodes fall
into this category. There are only a limited number of
radionuclide studies that compared baseline function
obtained during the early period after transplantation to that
obtained at the time of acute renal allograft dysfunction. In one
such study, a flat uptake curve with a relatively preserved
perfusion was observed in most low-grade AR episodes.49 This
pattern was suggested to represent a decrease in extraction
relative to perfusion. Significantly reduced uptake with a nearly
flat uptake peak was associated with decreased perfusion in the
setting of high-grade AR. This pattern was thought to represent
a relative increase in extraction in the face of a decrease in
perfusion. In the same study, several cases of biopsy-proven
“borderline changes” had the same renography pattern as lowgrade AR. The borderline changes can be interpreted at times
as a variant of normal and at other times as a variant of AR. In
most centers, cases with borderline changes in the setting
of deteriorating graft function with elevated creatinine levels
are treated as AR episodes, whereas those findings in the setting
of stable graft function are considered to be variants of
normal.50 Morphologic changes observed in cases of both
low- and high-grade ARs were an increase in graft size, loss of
corticomedullary differentiation with an increase in medullary
to cortex ratio, and little or no activity accumulation in
the collecting systems with or without pelvic hypoactivity.
These changes were thought to be due to edema in renal
interstitium and pelvicalyceal structures. Other than AR,
calcineurin inhibitor toxicity, glomerulopathy, infections, and
tubulointerstitial nephritis were among the common biopsy
findings. Differential diagnosis of AR in cases of acute renal
allograft dysfunction seems to be different than the early
postoperative differential consideration. In the presence of an
available comparative baseline study, the diagnosis of AR is
easier at this time than it is during the early posttransplantation
period. In the absence of ATN during this period, a single
imaging study can be diagnostic of a high-grade AR. The
specificity for low-grade AR is somewhat lower and can be
facilitated if a baseline study is available. DTPA and MAG3
findings in a renal transplant recipient with AR and serial
DTPA changes in low-grade and high-grade AR are
represented in Figures 2 and 3, respectively.
Evaluation of Subclinical Pathology. In renal transplant
patients with well-functioning grafts, the use of protocol
biopsies led to the identification of subclinical pathology.5
The potential benefit of early recognition and management
of these lesions may result in improved long-term outcomes. The most commonly identified pathologies are
subclinical or borderline rejection, transplant glomerulopathy, interstitial fibrosis, and tubular atrophy. Renal
scintigraphy findings in cases of subclinical pathology
and the effect of scintigraphic impairment on patient
management need to be determined.
Transplanted kidney function evaluation
Figure 2 (A and B) Posttransplantation day 7 Tc-99m DTPA images and renogram curve from a renal transplant recipient
with normal graft function. (C and D) Tc-99m DTPA renal images and renogram curve obtained 3 month after the first
study at a time when the patient had a diagnosis of low-grade acute rejection. There is a worsening of graft uptake with a
nearly flat curve. (E and F) Tc-99m MAG3 images and renogram curve in the patient obtained 1 day after the second DTPA
study. There is parenchymal retention of activity. (Color version of figure is available online.)
137
A. Aktas-
138
Figure 3 (A-C) Tc-99m DTPA images, perfusion time-activity curve, and renogram curve, respectively, in a patient with
low-grade AR. There is a flat uptake curve with a relatively preserved perfusion. (D-F) Tc-99m DTPA images, perfusion
time-activity curve, and renogram curve, respectively, in the patient 2 months later at a time when the patient had a
pathologic diagnosis of high-grade AR. Compared with the previous study, there is perfusion impairment with a loss of
peak-plateau pattern and a nearly flat uptake curve with a decrease in P:U indicating increased extraction as compared to
perfusion.
Evaluation of Slowly Deteriorating Graft Function. Chronic
allograft nephropathy (CAN) is the major cause of slowly
progressing graft dysfunction and graft loss after the first
posttransplantation year. Multifactorial risk factors for CAN
include DGF, repeated AR episodes, drug nephrotoxicity,
hyperlipidemia, and hemodynamic factors leading to
hyperfiltration and increased intraglomerular pressure. CAN,
which is often preceded or accompanied by hypertension and
proteinuria, is resistant to therapy with immunosuppressants.
Some centers perform protocol biopsies to diagnose this
condition at an early stage. Clear proof that protocol biopsies
improve long-term graft management and survival is lacking.
There is no established maintenance immunosuppressive
regimen that decreases the progression of CAN. Blockade of
renin-angiotensin system and the use of angiotensin II receptor
antagonist have been shown to increase survival and the level
of proteinuria significantly. There are a limited number of
radionuclide studies performed in patients with CAN. In one
such study, 63 patients with biopsy-proven CAN were
investigated using DTPA renogram curves.51 A progressive
change in perfusion-to-uptake pattern was observed, and
deterioration of perfusion preceded the decline in uptake.
Serial renogram changes were suggested to reflect initial
hypoperfusion, followed by increased intraglomerular
pressure, and finally glomerulosclerosis. In another study
that compared MAG3 and DTPA perfusion time-activity
curves, perfusion impairment could be observed with
equal sensitivity in cases of AR for both agents.52
However, the sensitivity of DTPA perfusion timeactivity curves to detect CAN was significantly higher
than MAG3 when only the second part of the perfusion
curve was taken into account. However, PI was
significantly higher than control group for both agents,
and the initial extraction slope was significantly lower
with MAG3. It seems that both agents are sensitive in the
detection of CAN, but with its different perfusion pattern,
DTPA may provide more specific information as to the
stage of CAN and predict response to treatment aimed
at renin-angiotensin system manipulation. DTPA and
MAG3 findings in a patient with CAN are represented
in Figure 4.
Evaluation of RAS. Hypertension is a common complication
observed after renal transplantation. Important risk factors
include immunosuppressive medications, complications
of transplant surgery, DGF, and rejection episodes.
Evaluation for renal artery patency should be conducted
in patients with severe hypertension refractory to medical
therapy. RAS is the most common vascular complication in
renal transplant recipients. It rarely occurs early after
surgery and most commonly occurs from months to
years after transplantation. Deterioration of perfusion on
Transplanted kidney function evaluation
139
Figure 4 A renal transplant recipient with chronic allograft nephropathy. (A and B) Tc-99m DTPA images and renogram
curve; (C and D) Tc-99m MAG3 images and renogram curve. On DTPA renogram curve, there is a loss of peak-plateau
pattern with a decrease in P:U value, indicating a high-grade parenchymal pathology. With MAG3, there is parenchymal
retention of activity. (Color version of figure is available online.)
DTPA after angiotensin-converting enzyme inhibitor
renography had a high sensitivity to detect transplant
RAS.53 Hemodynamically significant RAS was thought to
exhibit the same pattern as AR with decreased uptake
using DTPA and prolonged tracer transit using tubular
agents.40
Which Radiopharmaceutical Should Be Used
for Renal Transplant İmaging ?
After its first introduction as a Tc-99m-labeled renal imaging
agent, MAG3 was suggested to be superior to DTPA in cases
of impaired renal function owing to its higher extraction
fraction and better image quality. Therefore, most transplant
centers preferred MAG3 instead of DTPA in renal transplant
evaluation. However, only a limited number of studies in the
literature have compared the 2 agents together. Fraile et al54
studied 17 patients using both agents and found that in cases of
post–renal transplant failure and rejection, MAG3 was not
superior to DTPA significantly; moreover, in one case of
rejection, DTPA was superior to MAG3. Carmody et al55
studied 20 renal transplant recipients in the early posttransplantation period. They found MAG3 renography to be equal
to DTPA renography in assessing early transplant function. In
one study, patients with renal allograft dysfunction were
evaluated using DTPA and MAG3. Changes in the second
phase of the perfusion curve that reflected allograft dysfunction
were more common with DTPA.52 However, with the addition
of initial extraction slope, MAG3 proved to have similar
sensitivity to DTPA for detecting allograft dysfunction. It seems
that having better extraction efficiency may not correlate with
diagnostic superiority.
Most studies performed with MAG3 focused on the
estimation of anuric phase, evaluation of DGF, correlation of
scintigraphic parameters with biochemical markers, or prediction of short- and long-term graft survival. As for the
differential diagnosis of common early postoperative
A. Aktas-
140
complications, it is generally accepted that graft dysfunction
can be differentiated from normal function. In most studies
performed with MAG3, scan appearances were reported to be
similar in cases of ATN and AR. DTPA, having different scan
appearance and renogram curve pattern for ATN and AR,
offers more differential diagnostic power in cases of isolated
pathology. There are more studies in the literature with DTPA
than with MAG3, performed with the aim of differentiating
early posttransplantation complications. Sensitivity of DTPA
for detecting AR ranges between 62% and 90%.24,41,56 Such
a figure cannot be derived from the review of early posttransplantation MAG3 studies in the literature. There may be a
need to classify MAG3 renograms. It is more close to a flat
pattern in AR, whereas seems to be more accumulative in cases
of ATN. In addition to a nearly flat curve, a higher extraction
would be expected in low-grade AR as compared with ATN.
A higher renogram grade together with changes in the second
phase of perfusion curve might facilitate the diagnosis of highgrade AR with MAG3.
Most studies designed to evaluate the predictive power of
radionuclide renal imaging for short- and long-term graft
survival are performed with MAG3, and a strong correlation
between perfusion and nonperfusion parameters and graft
survival were documented. In the study by Gupta et al31 using
DTPA, PI was found to be strongest parameter for predicting
long-term prognosis. Because DTPA and MAG3 exhibit similar
PI values, both agents are expected to provide similar performance for this indication.
increased RI on Doppler sonography was seen in both
normal functioning grafts and those with allograft dysfunction on radionuclide imaging. 57 A scintigraphic
perfusion parameter was shown to be more sensitive
and specific than Doppler pulsatility index in differentiating well-perfused transplants than those with poor
perfusion.58 In the study by Fitzpatrick et al,59 serial
renal blood flow determinations with DTPA reflected
graft dysfunction more accurately than serial RI. In
a study that compared power Doppler sonography and
PI derived from DTPA scintigraphy, power Doppler was
found to be more sensitive than scintigraphy in the
detection of renal perfusion impairment; however, the
2 methods yielded similar specificity.60 Delaney et al56
compared the sensitivity of fine needle aspiration biopsy,
Doppler sonography, and radionuclide scintigraphy for
the diagnosis of acute allograft dysfunction among renal
transplant recipients. They identified radionuclide imaging as the most sensitive test (70%) for the diagnosis of
AR during the early posttransplantation period; the rates
of both Doppler sonography and fine needle aspiration
biopsy were considerably lower. Sensitivity of scintigraphy for acute cellular and vascular rejection episodes
were 62% and 90%, respectively.
Radionuclide Imaging vs Doppler Sonography
A single study alone may prove to be diagnostic in cases of
urinary leaks and renal artery thrombosis and may suggest the
presence of several early parenchymal complications. Radionuclide imaging may be more helpful in isolated cases of ATN
or AR. Initially accepted assumption of serial radionuclide
imaging during the early posttransplantation period to be
useful for a specific diagnosis is questionable. This necessitates
the transport of patient to Nuclear Medicine Department
several times during the first week or longer in cases of DGF.
Instead, a baseline study may be more useful as a comparative
tool for the diagnosis of AR episodes during the first year or
more after transplantation.
Blood flow velocity on spectral Doppler imaging is routinely
assessed during renal transplant sonography. Power Doppler
and color Doppler imaging improved the sensitivity of
evaluating renal microcirculation and low-velocity flow. The
RI is the most commonly used parameter derived from spectral
Doppler data for evaluating renal transplant dysfunction. It is
a measure of renal vascular resistance and thus provides
information on the hemodynamic status of the kidney.
Although some studies have shown RI to be valuable in the
assessment of renal transplant dysfunction, other studies were
inconclusive. Doppler sonography and radionuclide imaging
generally yielded higher sensitivity in cases of higher grades of
AR. Early perfusion changes as slight deteriorations in
peak-plateau pattern with DTPA or alterations in PI
observed with glomerular and tubular agents might be a
reflection of renal vascular resistance changes due to
parenchymal pathologies. More significant perfusion
impairments as loss of peak-plateau pattern and related
changes in renogram curves on DTPA might signify direct
vascular involvement in parenchymal pathologies as seen
in cases of vascular rejection. Correlative US and radionuclide imaging findings obtained during the early
posttransplantation period in several renal transplant
recipients are represented in Figures 5-7.
A limited number of studies in the literature have compared
Doppler findings with radionuclide imaging. In one study
performed during the early posttransplantation period, an
Conclusions and Suggestions
Diagnosis of Early Posttransplantation
Complications
Identification of Late Posttransplantation
Complications
The most commonly used imaging procedure for the evaluation of transplanted kidney is US. A review of literature reveals
that even this modality is seldom performed beyond 3 month
after transplantation for evaluating late parenchymal complications. For the most common late complication of transplantation, namely CAN, there are only a limited number of
studies performed with US. This number is even lower for
other imaging modalities. Imaging procedures at this time can
be used with even more safety as patient transport to imaging
unit is not a concern.
CAN is the major cause of late allograft loss. Its association
with DGF and repeated AR episodes is well documented.
Transplanted kidney function evaluation
Figure 5 (A and B) Ultrasonography images of a renal transplant recipient on posttransplant day 6. On gray-scale
sonography (A), there is increased echogenicity, renal cortical cysts, and perirenal fluid accumulation. On Doppler
sonography (B), increased RI values (0.80-0.84) were obtained from main renal artery, interlobar arteries, and segmental
arteries. Renal vein was patent. (C and D) Tc-99m DTPA images and renogram curve of the patient. There is a diffuse
peritransplant hypoactivity on early extraction images and a slight progressive increase in general background activity.
DTPA images and renogram curve exhibit a pattern resembling part ATN, part AR. (E and F) Posttransplant day 7 Tc-99m
MAG3 images and renogram curve of the patient. Diffuse peritransplant hypoactivity is not apparent on early images owing
to higher extraction of MAG3. There is a flat pattern on renogram curve suggestive of AR. Combined evaluation of DTPA
and MAG3 images suggest the presence of AR superimposed on ATN in its resolution stage. (Color version of figure is
available online.)
141
A. Aktas-
142
Figure 6 (A and B) Ultrasonography images from a renal transplant recipient on posttransplant day 6. There is significant
pelvicalyceal mucosal edema on gray-scale sonography (A) and homogenous distribution of perfusion on color imaging
(B). The patient had normal RI values. (C and D) Tc-99m DTPA images and renogram curve of the patient. There is a delay
in transit as evidenced by a delayed time to bladder visualization and pelvic retention of activity. Renogram curve is
accumulative. These findings suggest a pattern of partial obstruction owing to mucosal edema in the pelvicalyceal system.
(Color version of figure is available online.)
There is an association between DGF and AR that occur more
than 1 year after transplantation.32 Late AR episodes are
reported to have more negative effect on graft survival as
compared with early ones.61 Radionuclide imaging can be
used for the diagnosis of late AR in high-risk patients. It has the
unique advantage of relating perfusion to function. Although
most radionuclide studies in the literature evaluated either
perfusion or function separately, relating these 2 parameters
may be more important in the evaluation of late posttransplantation complications. This information might reveal data
regarding the functional evolution of CAN and may have the
potential of affecting patient treatment protocols. Comparative
studies with protocol biopsies at certain predetermined
intervals after the transplantation may provide useful information in patient management. In this way, the potential of
radionuclide imaging to replace protocol biopsies can be
identified.
Comparative Studies Between İmaging
Modalities
Radionuclide imaging and Doppler sonography seem to have
similar performance in evaluating renal transplant perfusion.
However, scintigraphy has the added advantage of providing
functional information. Comparative studies with contrastenhanced sonography and scintigraphy may be needed for
differentiating parenchymal pathologies. A similar study can
be conducted for evaluating perfusion and function impairment in cases of CAN.
Patient Management
In most transplant centers, the first response to deterioration of
transplant function is the initiation of pulse steroid treatment.
In cases of subclinical rejection or borderline cases, the decision
Transplanted kidney function evaluation
143
Figure 7 (A) Posttransplant day 3 US of a renal transplant recipient with uncomplicated early postoperative course. Finding
of Gray-scale sonography was normal. On Doppler imaging, there is decreased RI (0.46-0.50) on the interlobar and
segmental arteries. (B) Doppler US of the patient at 1 month after transplantation. Normal RI values were obtained from
interlobar and segmental arteries. (C and D) Tc-99m DTPA images and renogram curve of the same patient on day 3 after
transplantation. There is a pattern of hyperperfusion with decreased time to excretion. On renogram curve, hyperperfusion
pattern is evident with increased ratios of P:PL and P:U. In recipients with an uncomplicated early posttransplantation
course, combined evaluation of Doppler parameters with scintigraphy results might reveal the postoperative physiological
nature of the observed changes. (Color version of figure is available online.)
to treat or not may be based on functional impairment detected
on scintigraphy. In cases of AR, initiating treatment with
steroids or more aggressive options such as monoclonal
antibody induction therapy may be based on scintigraphy
findings.62 Comparative studies with protocol biopsies might
be needed in cases of subclinical pathology for identifying the
role of radionuclide imaging in patient management.
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