doi:10.1053/j.semnuclmed.2005.08.002

Pediatric Applications of Renal Nuclear Medicine

Amy Piepsz, MD, PhD,* and Hamphrey R. Ham, MD, PhD

†

This review should be regarded as an opinion based on personal experience, clinical and

experimental studies, and many discussions with colleagues. It covers the main radionu-

clide procedures for nephro-urological diseases in children. Glomerular ﬁltration rate can

be accurately determined using simpliﬁed 2- or 1-blood sample plasma clearance methods.

Minor controversies related to the technical aspects of these methods concern principally

some correction factors, the quality control, and the normal values in children. However,

the main problem is the reluctance of the clinician to apply these methods, despite the

accuracy and precision that are higher than with the traditional chemical methods. Inter-

esting indications are early detection of renal impairment, hyperﬁltration status, and

monitoring of nephrotoxic drugs. Cortical scintigraphy is accepted as a highly sensitive

technique for the detection of regional lesions. It accurately reﬂects the histological

changes, and the interobserver reproducibility in reporting is high. Potential technical

pitfalls should be recognized, such as the normal variants and the difﬁculty in differentiating

acute lesions from permanent ones or acquired lesions from congenital ones. Although

dimercaptosuccinic acid scintigraphy seems to play a minor role in the traditional approach

to urinary tract infection, recent studies suggest that this examination might inﬂuence the

treatment of the acute phase, the indication for chemoprophylaxis and micturating cystog-

raphy, and the duration of follow-up. New technical developments have been applied

recently to the renogram: tracers more appropriate to the young child, early injection of

furosemide, late postmicturition and gravity-assisted images and, ﬁnally, more objective

parameters of renal drainage. Pitfalls mainly are related to the interpretation of drainage on

images and curves. Dilated uropathies represent the main indication of the renogram, but

the impact of this technique on the management of the child is, in a great number of cases,

still a matter of intense controversy. Direct and indirect radionuclide cystography are

interesting alternatives to the radiograph technique and should be integrated into the

process of diagnosis and follow-up of vesicoureteral reﬂux.

ediatrics is a specialized ﬁeld of application of nuclear

medicine and many centers are still reluctant to perform

radionuclide tests in children. The practical aspects of con-

ducting the examination undoubtedly constitute the main

difﬁculty: preparation and information of patient and par-

ents, the capacity to handle the natural anxiety related to the

procedure, the creation of a friendly environment (waiting

room and gamma camera room), adequate immobilization of

the patient, adaptation of the acquisition to the size of the

patient (zoom and pinhole views), and the administration of

intravenous injections and blood sampling with minimal dis-

comfort for the child. In addition, special attention should be

given in this young age group to the problems of radiation

protection and the variation in function of age of the biolog-

ical distribution, uptake, and retention of radiopharmaceuti-

cals. Similarly, numerous difﬁculties and pitfalls in the inter-

pretation of images and functional parameters are evident

during maturation. Finally, although many indications for

nuclear medicine procedures are common to children and

adults, there is a wide panel of speciﬁc pediatric indications

of which the nuclear medicine physician should be aware.

Nephro-urology is probably the best illustration of this

speciﬁcity. Although generally not more than 5% of the

workload of a nuclear medicine department is devoted to this

subspeciality, more than 60% of the pediatric examinations

are aimed at exploring the urinary tract.

There are 2 main reasons for this difference. First, urinary

tract infection is frequent in childhood, and approximately

80% of ﬁrst infections occur before a child reaches 2 years of

*Centre Hospitalo-Universitaire St Pierre, Department Radioisotopes, Brussels,

Belgium.

†Department Nuclear Medicine, University Hospital Ghent, Ghent, Bel-

gium.

Address reprint requests to Amy Piepsz, MD, PhD, CHU St Pierre, Depart-

ment of Radioisotopes, 322, Rue Haute, B-1000 Brussels, Belgium.

E-mail: [email protected]

doi:10.1053/j.semnuclmed.2005.08.002

age. Association with structural abnormalities such as under-

lying vesico-ureteric reﬂux is not rare, and complications

such as severe recurrent infections, scarring, loss of renal

function and, in the long term, hypertension constitute a

constant preoccupation for the pediatrician. Second, prenatal

screening has led to the detection of a large number of uro-

nephrological abnormalities. It is therefore understandable

that the clinician is tempted to prevent further deterioration

of the kidney. Nuclear medicine offers the possibility of eval-

uating, from the very early weeks, the function of the urinary

tract, and the effect of any medical or surgical treatment.

What is the beneﬁt of all these examinations? We are now

at a point where many uncertainties related to the procedures

have been clariﬁed. Most of the uronephrological techniques

ar now better understood and are almost standardized. Some

pitfalls of interpretation are known, the levels of sensitivity

and speciﬁcity have been largely evaluated, robustness in

reporting on a test has been checked on many occasions and

experimental studies have validated these procedures.

However, there still is a long way to go, and we need much

more rigorous work to evaluate the real utility of these exam-

inations. Although we can identify the acute lesion of pyelo-

nephritis, we still need to prove that the acute dimercapto-

succinic acid scintigraphy (Tc-99m DMSA) can modify the

strategy of treatment and follow-up. A renal scar can be

shown much easier than with the classical intravenous urog-

raphy, but we still do not know what the consequence will be

for the patient having 1, 2, or multiple scars. Are we forced to

continue conducting the very unpleasant direct cystography

in a 2-year-old child simply because of acute pyelonephritis,

or, will a normal DMSA scan allow us to spare patients many

unnecessary tests? Having the possibility of regularly evalu-

ating the renal function of a hydronephrotic kidney by using

renography already has completely changed the strategy of

the surgeon and, although many uncertainties related to the

criteria of surgery still remain, it is already very clear that only

a minority of these children will now undergo surgery com-

pared with the systematic surgical approach one generation

earlier.

The details of the radionuclide procedures used in pediat-

ric uronephrology are presently described in detail in various

American and European guidelines and will be cited within.

However, guidelines generally are a compromise between

different opinions, based or not on solid evidence. This re-

view should be regarded as an opinion based on personal

experience, clinical, and experimental studies and numerous

debates with clinicians involved in this particular ﬁeld of

medicine. Several technical aspects related to these proce-

dures will be examined, but it was our feeling that, at the

present time, more attention should be paid to the potential

impact these techniques may have in the strategy of pediatric

uronephrology.

Glomerular Filtration Rate (GFR)

Physiology

GFR generally is accepted as the most representative param-

eter of renal function. It is relatively constant under standard

conditions and, as opposed to tubular secretion, is indepen-

dent of the urine ﬂow. Because GFR may be reduced before

the onset of symptoms of renal failure, its assessment enables

earlier diagnosis and therapeutic interventions in patients at

risk. Moreover, the level of GFR is a strong predictor of the

time of onset of kidney failure as well as the risk of compli-

cations of chronic kidney disease.

Chemical and Radionuclide Methods

Inulin clearance with constant infusion and an indwelling

catheter is the “gold standard” but is used only for research.

Serum creatinine is a simple chemical parameter for a ﬁrst-

step gross evaluation of renal function. However, it is a poor

guide to GFR because it is highly dependent on muscle mass

and it is insensitive to changes in renal function until glomer-

ular ﬁltration is reduced substantially. It is, for instance, ob-

vious, from the nonlinear relation between plasma concen-

tration and clearance, that as much as half of the renal

function can be lost before any signiﬁcant increase of plasma

creatinine occurs. On the contrary, the sensitivity of plasma

creatinine for GFR changes is great once GFR decreases to

less than 15 mL/min.

Schwartz’s nomogram, particularly popular among pedi-

atric nephrologists, has been established to predict creatinine

clearance from plasma creatinine concentration, taking the

age, gender, and body weight into account.

The accuracy of

this nomogram is controversial, although it is often consid-

ered by some as sufﬁcient for clinical use. The error in pre-

dicting the true clearance can be considerable and, like the

plasma creatinine, the nomogram is unable to detect early

changes in renal function. True GFR measurements are

needed to identify early decline in kidney function. The al-

gorithm is not reliable in children with insulin-dependent

diabetes mellitus,

in liver disease,

4,5

and after liver transplan

tation.

Its use is inaccurate for the estimation of GFR in

healthy potential kidney donors,

whereas, for those who

GFR values are less than30 mL/min/1.73 m

, the overestima

tion can reach 67%.

Creatinine clearance necessitates a pre

cise urine collection which, in routine situations, represents

the main source of imprecision, particularly in young chil-

dren.

Plasma sample radionuclide clearances allow the detection

of early renal impairment and an accurate estimation of hy-

perﬁltration. Precise monitoring of GFR changes can be ob-

tained, for instance, during nephrotoxic chemotherapy, for

the entire range of GFR levels down to ⫾ 15 mL/min/1.73 m

However, it is obvious that radionuclide estimation of

overall GFR has not gained wide acceptance among pediatric

nephrologists. Several factors have contributed to this lack of

interest: a strong conﬁdence in the daily used chemical tech-

niques, even if biased by major errors; the price of the radio-

pharmaceutical and the radiation dose (even if negligible be-

cause of the small doses used for determining the plasma

concentration); and the nonstandardization for many years of

the radionuclide technique, which has led to inaccurate re-

ports and loss of conﬁdence in the results. One can only hope

that the consensus conferences,

and the recently published

Pediatric applications of renal nuclear medicine

guidelines

may help to restore conﬁdence in one of the

most accurate quantitative techniques in nuclear medicine.

Finally, the attitudes related to this technique are essentially

variable from country to country and from department to

department. In some countries, such as Italy, the pediatri-

cians only rarely use the plasma samples technique, whereas

in others, such as Denmark, Sweden, or the United Kingdom,

these techniques represent the best approach for accurate

and simple measurement of overall renal function.

Tracers

The measurement of GFR can be obtained by means of radioac-

tive tracers exclusively eliminated by the glomerulus. Chro-

mium-51 ethylenediamine tetraacetic acid (51Cr-EDTA) is

probably the best tracer for that purpose, because of the tight

binding of Chromium-51 to EDTA and the low protein bind-

ing of the compound. However, it is not universally available.

A valuable alternative is the use of technetium-99m diethyl-

enetriaminepentaacetic acid (

99m

Tc-DTPA), providing that

the purity is guaranteed. The use of

99m

Tc-DTPA requires

systematic quality controls.

11-13

The various algorithms de

signed for the calculation of GFR have been applied using

indifferently both tracers.

Algorithms for Clearance Determination

The most accurate method for evaluating GFR by means of

radionuclides is based on the plasma disappearance curve

after a single bolus injection of a glomerular tracer. It has

been shown that a biexponential ﬁtting on the plasma curve

is an acceptable representation of the true clearance.

How

ever, this method, which is presently considered as a “gold

standard,” is used infrequently in children because of the

difﬁculties related with multiple blood sampling. Two accu-

rate simpliﬁed methods have been proposed for clinical rou-

tine in children.

The Slope-Intercept Method

This method is based on the determination of only the late

exponential by means of at least 2 blood samples at 2 and 4 h

after the intravenous injection of the tracer. The intercept

with the y-axis determines the initial distribution volume of

the tracer, and the product of distribution volume and slope

allows the calculation of the clearance.

9,10

This simpliﬁed

method has been validated in both adults and children.

15-17

However, some details of the procedure are still a matter of

debate, as detailed in the following subsections.

Number of Blood Samples to Be Taken. Two blood samples,

taken at 2 and 4 h, allow an accurate estimate of the slope. It

has been suggested that the slope could be more accurately

determined using 4 samples between 2 and 4 h

because an

error in one of the samples could then be easily detected.

However, it has been shown

that as many as 13 blood

samples are required to increase signiﬁcantly the accuracy of

the slope.

Correction Factor for Having Neglected the Early Exponen-

tial. By neglecting the early rapid exponential, one intro-

duces a systematic overestimation of the clearance, which can

be corrected using 2 different published algorithms adapted

to children, the Chantler’s method

and the Bröchner-

Mortensen’s correction.

In theory, Bröchner-Mortensen’s quadratic correction

takes better account of the higher contribution of the early

exponential for high clearance values. In the practice, in the

range of clearance values higher than 140 mL/min/1.73 m

the error introduced by this correction is not to be neglected.

Indeed, this quadratic equation has been established on the

basis of clearance values not greater than 130 mL/min/1.73

and it is easy to show mathematically that, using this

correction factor, one cannot obtain clearance values higher

than 150 mL/min/1.73 m

. In other words, the Bröchner-

Mortensen’s correction underestimates GFR values greater

than 100 mL/min/1.73/m

and introduces a considerable

compression of the clearance values higher than 140 mL/

min/1.73 m

. Monitoring of hyperﬁltration, a well-known

feature of nonequilibrated juvenile diabetes, will therefore be

seriously hampered by using this correction factor.

The Chantler’s correction is a simple proportional correc-

tion, applied to all levels of renal clearance, thus neglecting

the increasing weight of the ﬁrst exponential for high clear-

ance values. Another drawback, underlined by the British

Nuclear Medicine Society (BNMS) guidelines,

is the fact

that this correction factor has been determined on a mixed

population of adults and children older than 5 years of age.

However, the errors introduced by using this correction fac-

tor might be less important than the compression of high

clearance values using BM formula.

Quality Control. One can check the distribution volume ob-

tained. It is generally considered that the distribution vol-

ume, obtained by interpolation of the slope on the y axis,

represents the extracellular volume, which is expected to be,

in human beings with normal or subnormal renal function,

around 20 to 30% of body weight. In clinical practice how-

ever, this distribution volume, which is a simple mathemat-

ical interpolation and not a direct measurement, tends to vary

in a much greater proportion. However, distribution vol-

umes below 15% or above 50% should raise the suspicion of

a signiﬁcant error on any of the measurements mentioned

hereby. In case of signiﬁcant peripheral edema, any method

exclusively based on plasma samples is invalid.

The Single Blood Sample Method

This method is an entirely empirical one, aimed to ﬁnd the

best possible correlation between a reference method and a

plasma concentration at a given time. According to the com-

plex relation existing between the slope-intercept method

and the so-called “distribution volume” method, one can

only determine an adequate sampling time for a given range

of clearance values.

Several algorithms have been described.

21,22

One of them

is based on a single blood sample taken at 2 h and offers 2

signiﬁcant advantages: the algorithm has been established on

a basic set of children and tested successfully on a second set.

Moreover, the algorithm has proven to be applicable what-

A. Piepsz and H.R. Ham

ever the age of the patient, the coefﬁcient of correlation be-

tween the single blood sample and the 2 blood sample meth-

ods being close to 1.0 for all ages. Recently, it has been

shown

that the algorithm remains valid for adolescents and

young adults. The only major limitation is the level of clear-

ance: the method is not valid below 30 mL/min/1.73 m

.In

case of known or suspected renal insufﬁciency (clearly ab-

normal plasma creatinine) one should use the slope-intercept

method.

The main advantage of the technique is the unique blood

sample needed. A 27 Butterﬂy needle for intravenous injec-

tion and a 25 Butterﬂy needle for blood sampling replace

favorably the more aggressive Venﬂon needle, particularly in

infants. According to the BNMS guidelines,

the drawback of

the single blood sample technique is the absence of quality

control, since the slope of the late exponential cannot be

determined anymore. It is however possible to get the same

level of quality control as for the slope-intercept method, by

creating artiﬁcially three different slopes, using arbitrary

20%, 25%, and 30% distribution volumes and calculating on

that basis 3 different GFR values; a signiﬁcant difference be-

tween the single sample clearance and the three calculated

GFR indicates the presence of error.

Normal GFR Values

Estimated normal values, corrected for body surface, have

been published.

The clearance level, uncorrected for body

surface, increases progressively from birth to adulthood. The

clearance, corrected for body surface area, increases from

birth to approximately 2 years of age and then remains con-

stant into adulthood. One major inaccuracy related to that

publication has to be raised. Normal values were derived

from young patients generally referred to the department of

nuclear medicine because of acute pyelonephritis. The pa-

tients included in the study all had a normal left to right

DMSA uptake ratio and no regional abnormalities on the

DMSA images and were, on that basis, considered normal.

The authors, at the time of the publication, were not aware of

the fact that acute renal infection could result in severe hy-

perﬁltration, in a kidney with or without DMSA defects.

26,27

New data, excluding acutely ill patients, have recently been

analyzed. The same pattern of GFR, corrected for body sur-

face, reaching an adult level around 2 years of age, was ob-

served (Piepsz and coworkers, unpublished data). Although

the range of normality in children after 2 years of age remains

unchanged (80 and 140 mL/min/1.73 m

, respectively for

percentiles 5 and 95), the mean normal value is signiﬁcantly

lower (104.4 mL/min/1.73 m

instead of the previously re

ported 113.9 mL/min/1.73 m

Accuracy and Reproducibility

of Simpliﬁed Methods

The wide range of normal values, in children older than 2

years of age, represents the physiological ﬂuctuations of GFR

from patient to patient rather than methodological ﬂaws.

Indeed it should be underlined that in younger children, and

particularly in infants, the range is much smaller. The GFR,

not corrected for body surface area, in infants younger than 1

month of age, is close to 10 mL/min, with a small SD of

4 mL/min, suggesting that the methodological error is small,

whatever the age.

The day to day reproducibility is a matter of controversy. It

has been suggested by the BNMS guidelines

that at least a

20% change is required before a measured difference can be

regarded as signiﬁcant. This number mainly is based on a

retrospective study of patients with chronic renal disease fol-

lowed for a long period of time.

Such a cut-off level should

fundamentally question the utility of this type of clearance.

However, better reproducibility has been observed by oth-

ers

29,30

and the conclusions of these guidelines should prob

ably be less afﬁrmative, until a prospective well-designed

study clariﬁes the subject. Anyway, a similar level of day-to-

day reproducibility is observed for the reference biexponen-

tial method and for the simpliﬁed methods, while the use of

the slope alone for estimating GFR results in a lower repro-

ducibility.

31,32

The reproducibility is even better for the single

blood sample method than for the slope-intercept method.

Clinical Indications

Determining GFR by means of radioactive tracers can be

useful in the following situations (1) evaluation and fol-

low-up of renal function in chronic glomerular diseases, such

as hemolytic-uremic syndrome and diabetes mellitus; (2)

evaluation and follow-up of renal side effects of nephrotoxic

drugs, such as ciclosporin or antibiotics; (3) estimation of

absolute single-kidney GFR, by combining overall GFR with

the split function obtained by means of the renogram (please

see the section, “The Renogram”), in conditions such as uni-

lateral or bilateral hydronephrosis, urinary tract infections

with or without associated vesico-ureteral reﬂux, small kid-

ney, single kidney, duplex kidney, urethral valves, pre- and

postoperative follow-up; and (4) it can be considered every

time renal impairment is suspected, even when plasma cre-

atinine is in the normal range.

Conclusions

The determination of overall renal function by means of

plasma sample radionuclide technique has multiple advan-

tages in pediatric practice: (1) it offers an accurate measure-

ment of renal function for clearance values above 15 to

20 mL/min/1.73 m

; (2) it represent a noninvasive approach

(one intravenous injection and one or two blood samples),

friendly to the child, delivering a rather negligible amount of

radiation; and (3) it provides an information signiﬁcantly

more accurate than the nonradioactive traditional measure-

ments.

Cortical Scintigraphy

Tracers

There is presently a wide consensus on the preferential use of

DMSA labeled with Technetium-99 m for cortical scintigra-

phy.

The tracer is taken up by the proximal tubular cells,

directly from the peritubular vessels, and is therefore located

Pediatric applications of renal nuclear medicine

in the outer layer of the kidney with minimal activity in the

medulla and the calyces. In 2 speciﬁc conditions however,

the excretion of the tracer can signiﬁcantly interfere with the

interpretation of the images. In pronounced hydronephrosis

with marked delayed transit, the excreted renal activity may

accumulate in the calyces and pelvis, altering artiﬁcially the

intrarenal tracer distribution. In Fanconi syndroms, the

DMSA escapes the tubular cell and is found mainly in the

urine, resulting in low renal activity.

Alternative tracers for renal imaging are those with a high

excretion rate used for renography, such as Tc-99m MAG3

and I-123 Hippuran. They offer the advantage of combining

cortical imaging with information about renal transit. They

are however less accurate for the detection of cortical defects.

Tc-99 m glucoheptonate is partly bound to the renal tubules

and can be used for cortical imaging. However, the cortical

uptake is signiﬁcantly less than with DMSA. Moreover, as

much as 40% to 65% of the tracer is excreted, and this may

interfere with the activity retained within the cortex and com-

plicate the interpretation of the images.

Acquisition Procedure

Much effort has been devoted recently to the production of

consensus and guidelines in this ﬁeld.

34-36

Having an immo

bile child during the whole acquisition is mandatory for the

quality of the image. However, drug sedation generally can be

avoided. Images should be acquired 2 to 3 h after tracer

injection. The collimator should be turned side up and the

patient should lie on the camera in supine position. A high-

resolution collimator is required. The matrix should be at

least 128 ⫻ 128. At least 300,000 counts or 5-min counting

per image are necessary. Pinhole views (2- to 3-mm aperture)

may be useful, particularly in infants, but this technology is

not used universally. There is still a need for a systematic

approach to the normal and abnormal pinhole images. Pos-

terior and posterior oblique views are recommended. How-

ever, it has been shown that the posterior view offers the most

information concerning cortical integrity and should receive

the highest priority. Obliques views may sometimes contrib-

ute to a change in the ﬁnal report, although unusual.

The

anterior view should be performed in horseshoe kidney and

in ectopic pelvic kidney.

Reporting and Image Quality

Reporting is preferably performed directly on the computer

screen. A gray scale should be used rather than color images.

The intensity of the image should be adapted to allow differ-

entiation of the outer part of the kidney (cortex) and the

less-active inner part (medulla, calyces, vascular structures).

In a crying child, the kidneys are moving with the dia-

phragma, even if the child remains immobile. It is important

to check for kidney movement before the child leaving the

department: blurred or double outlines generally reﬂect the

presence of movement.

Interpretation of Images

The interpretation of the images generally is easy, although

one should be aware of the existence of several normal vari-

ants, including spleen impression, variability in the shape of

the renal contours, number and size of the columns of Bertin,

persisting fetal lobulation, and poles appearing as hypoac-

tive. For those clinicians not accustomed to the DMSA, the

main pitfall in interpretation is probably a relative hypoactiv-

ity of a pole, contrasting with an underlying huge parenchy-

mal mass and thus giving a false impression of a polar lesion.

Lesions are described as single or multiple, small or large,

with or without volume loss. The renal contours limiting the

lesion can be indistinct but still regular, or on the contrary

irregular, corresponding to a loss of parenchymal mass. The

kidney can be small or swollen. When observed during the

acute phase of pyelonephritis, hypoactive areas without de-

formity of the countours are likely to become normal during

a late control image, whereas deformed countours often cor-

respond to renal sequelae. However, it is not recommended

to conclude the presence of renal sequelae on an “acute”

DMSA. Permanent lesions can only be reported on the basis

of late control studies at least 6 months after the acute infec-

tion. One should be aware of the fact that a persistent lesion

is not necessarily a sequel of the most recent acute pyelone-

phritis but may be related to a previous one, or may even be

congenital (dysplasia). There is at the present time no con-

sensus about the usefulness of single-proton emission com-

puted tomography (SPECT) for DMSA scintigraphy in chil-

dren, although it may help in individual cases. When

performing SPECT, attention must be paid to the risk of

false-positive images

38,39

and to the necessity of heavy seda

tion in young children. It has been shown that SPECT images

decrease the reproducibility in reporting on DMSA scintigra-

phy.

Sensitivity and Speciﬁcity

There is much evidence that DMSA scintigraphy is more

sensitive than intravenous urography, ultrasound and even

color Doppler in the detection of both acute lesions and late

sequelae.

41,42

On the contrary, scintigraphic abnormalities

are not speciﬁc: in case of acute urinary tract infection, re-

gional defects can be attributable to acute infection but also to

any other underlying disease, such as renal abscess, hydro-

nephrosis, cysts, or duplex kidney with abnormal upper or

lower moiety. It is therefore mandatory to combine scintig-

raphy with a technique, which allows one to differentiate

between these situations: ultrasound has a low sensitivity for

acute pyelonephritis but is useful in excluding any expansive

lesion or huge dilation of calyces and pyelum.

Validation

Animal models combining vesicorenal reﬂux and infection

have shown the relation between the extension of the ana-

tomical lesion (acute lesion or scarring) and the presence of a

scintigraphic abnormality.

DMSA scintigraphy is normal in

the absence of an anatomical lesion and only microscopic

lesions, unlikely to give rise to scars, are missed on DMSA

images.

A. Piepsz and H.R. Ham

Reproducibility in Reporting

Poor as well as good interobserver reproducibility has been

observed. A recent large study involving a great number of

nuclear medicine physicians revealed a high concordance on

normality or abnormality.

A similar level of interobserver

reproducibility was reached, whether the lesion was acute or

limited to a late scar.

This does not eliminate that in a

signiﬁcant number of cases, great discordance might be

noted between different observers. Factors such as quality of

images, lack of awareness of the normal patterns, and low

renal function, may contribute to a poor reproducibility.

Relative Function

The determination of left and right relative DMSA uptake is

an accurate and robust quantitative measurement and should

be systematically added to the scintigraphic images. Because

of the high signal-to-noise ratio, background correction is

probably not mandatory in cases with good renal function. A

background can be introduced, however, by drawing for in-

stance a small region of interest (ROI) above each kidney and

another under each kidney, avoiding the bladder activity. In

case of renal failure, this correction method is inaccurate.

Correction for attenuation is not mandatory for relative func-

tion, except in the case of ectopic kidney anteriorly displaced.

However, in case of pelvic kidney, the relative function re-

mains inaccurate even after attenuation correction, because

of the additional attenuation resulting from the pelvic bone.

It has been shown that interobserver reproducibility of rela-

tive function measurement generally is good.

The normal

lowest value for relative uptake usually is around 45%.

Absolute Function

Determination of absolute function of each kidney separately

by means of DMSA is used in different departments around

the world. The renal counts at a given time are expressed as a

percentage of the injected dose. The results were shown to be

only fairly correlated with reference techniques, even when

using SPECT.

47,48

Factors that may inﬂuence both the accu

racy and the day-to-day reproducibility are the exact estima-

tion of kidney depth, the timing of measurement,

and the

quality of the preparation injected.

Is DMSA Scintigraphy

Useful in Clinical Practice?

The area of highest controversy is probably the place of cor-

tical scintigraphy in the strategy of investigations in urinary

tract infection (UTI). In children, 3% to 5% of girls and 1% to

2% of boys have had a symptomatic UTI,

and most of the

ﬁrst infections occur in children younger than 2 years of age.

The traditional attitude is to deﬁne “complicated” urinary

tract infection on the basis of clinical and biological criteria,

to treat this entity in a more aggressive way than in the case of

simple cystitis, to prescribe a prophylactic treatment to pro-

tect the kidney from further deterioration, to perform sys-

tematically a micturating cystography to diagnose the grade

of vesico-ureteric reﬂux, and to treat dysfunctional bladders.

Having this approach in mind, DMSA scintigraphy has no

place either for the diagnosis of acute pyelonephritis or for

adapting later on the strategy of management. It has been

suggested

that even ultrasound is unnecessary, since un

derlying hydronephrosis is already detected during fetal life.

This general attitude, based on clinical data, makes sense and

is adopted by many centers around the world. However,

attitudes based on high-risk groups are emerging that might

change our traditional practice in a near future.

Diagnosis of UTI

There is no doubt that the diagnosis of UTI relies on a urine

culture obtained from a properly collected urine sample.

Theoretically, there is no place for imaging in that perspec-

tive. However, it has been shown in a prospective work per-

formed in 2 different hospitals

that as many as 10% of

children with strong clinical suspicion of acute pyelonephri-

tis may present with repeated negative or equivocal cultures

despite a positive DMSA scintigraphy (Fig. 1). One could

argue about the fact that DMSA lesions might in those cases

have preceeded the infection. However, this is not the case

because many of these lesions disappeared at late control.

One can easily understand that in that subgroup of patients,

the diagnosis of complicated infection would have been

missed entirely in the absence of scintigraphy.

Diagnosis of Acute Pyelonephritis

It is now an old tradition to diagnose upper UTI on the basis

of clinical and biological symptoms, such as fever, septic

signs, loin pain, high C-reactive protein, and an elevated

number of white blood cells in peripheral blood. The valida-

tion of these criteria can be debated. It is based on bladder

washout and ureteral catheterization studies performed on a

limited number of patients before 1950. The results are open

to criticism.

Patients with a full clinical picture of compli

cated UTI may or may not present with abnormalities on

DMSA scintigraphy performed within the ﬁrst week of infec-

Figure 1 A 4-month-old boy with high fever, and repeated urine

cultures that were negative. The DMSA scintigraphy shows impor-

tant hypoactivity of the right upper pole, with deformity of renal

outlines. The child was treated for acute pyelonephritis on the basis

of the scintigraphy. A control scintigraphy 6 months later was en-

tirely normal, conﬁrming retrospectively the diagnosis of acute py-

elonephritis.

Pediatric applications of renal nuclear medicine

tion.

55-62

When analyzing the largest series of acute pyelone

phritis (Table 1), it appears that approximately 65% of cases

will present cortical abnormalities corresponding to the ex-

pected histological lesion. One of 3 patients considered as

having acute pyelonephritis has no DMSA lesion. The risk for

developing scars for a kidney with an acute DMSA lesion can

reach 30%.

60,62

It is negligeable in case of normal DMSA.

Treatment of Acute Pyelonephritis

Several surveys and questionnaires are available concerning

the way the clinicians are treating their patients. Some of

them,

63,64

covering an entire region or even a country, have

come to the conclusion that admission to the hospital and

intense intravenous treatment is dependent mainly on the

subspeciality of the clinician (general practitioner, general

pediatrician, pediatrician working in hospital, or pediatric

nephrologist) rather than on some objective clinical criteria.

A recent personal small survey (unpublished) on 20 depart-

ments of pediatric nephrology in Europe (7 countries) has

shown that most of the departments recommend intravenous

treatment. The proposed duration of intravenous treatment

was 1 to 3 days (34%), 5 to 7 days (33%), and 7 to 10 days

(27%). A French consensus

recommends 7 to 10 days of

aggressive intravenous treatment in young or very ill chil-

dren. Hoberman and coworkers

propose an oral treatment

with third-generation cephalosporins and consider intrave-

nous treatment as unnecessary.

Which attitude should be applied ? Hansson and Jodal

consider that “local traditions and beliefs guide the choice of

treatment strategy. Controlled studies are lacking. ” Indeed,

there are presently not more than 3 published prospective

randomized studies

60-62

comparing, in acute pyelonephritis,

2 types of treatment. One of them is issued from our group

and showed that, in case of delay in treatment (more than 7

days after appearance of the ﬁrst symptoms), more scars were

noted at late control in the group having received 3 days of

adequate intravenous treatment compared with the group

treated intravenously for 7 days.

On the basis of this study, the following procedure has

been deﬁned in our department: children admitted for acute

pyelonephritis are treated intravenously for 7 days. DMSA

scintigraphy is performed systematically within 2 days of

admission and intravenous treatment is stopped after 24-

hour apyrexia if the scan is normal. This is an example on

how the type of treatment can be modulated on the basis of

the acute DMSA. A similar approach has been proposed else-

where.

Performing Micturating Cystography (MCUG)

A worldwide classic approach is to perform MCUG in any

ﬁrst UTI, to detect a vesico-renal reﬂux, and to modify the

management of the patient. However, attitudes vary from

center to center, the systematic indication of MCUG being,

for instance, restricted to young children or to patients pre-

senting with recurrent infections. The rationale for a system-

atic approach of reﬂux in case of infection is the close rela-

tionship described between reﬂux and scarring. A recent

meta-analysis comparing DMSA patterns to the results of

MCUG suggests that this relationship is not proven, with

reﬂux often being associated with a normal kidney, whereas

many scarred kidneys are observed in the absence of any

reﬂux.

This apparent contradiction is probably attributable

to 2 main errors in the design of many studies. First, the

results of DMSA scintigraphy often are compared with

MCUG without taking into account the timing of DMSA scin-

tigraphy. There is no doubt that during the acute phase of

infection, DMSA lesions can be seen with or without reﬂux,

without evident correlation between the 2 parameters.

Sec

ond, a simple correlation between reﬂux and scarring does

not take into account the fact that low-grade reﬂux (I and II),

which is the most common type in case of UTI, is associated

with a low risk of scarring.

The International Reﬂux Study,

in which 287 children

were allocated on the basis of UTI and high-grade reﬂux

(mostly grade IV) has revealed at entry as much as 80% of

unilateral or bilateral scarring, which is much higher than

what is observed in any population selected only on the basis

of complicated UTI. A recent study

clearly showed that the

more important the grade of reﬂux, the higher the number

and the intensity of scars. On the basis of that association, it

was interesting to see whether the presence of renal scarring

on the DMSA scan could be an indicator for the decision to

perform a MCUG in children with UTI. In this retrospective

study on 303 children younger than 2 years, only 7 patients

were found with normal DMSA images and high-grade reﬂux

(grade III). In these patients, no scarring was noted during

follow-up. It might be that DMSA scintigraphy could replace

MCUG as a ﬁrst-line investigation, this last examination be-

ing then performed only in case of abnormal DMSA. This

strategy would spare a great number of unnecessary, unpleas-

ant and invasive procedures. It has to be conﬁrmed in a long

term prospective study.

Indication for Chemoprophylaxis

Since Smellie’s pioneer work,

continuous chemoprophy

laxis is widely given, sometimes for many years, to children

with UTI and reﬂux. Recently, a meta-analysis has put this

systematic approach in question.

Present attitudes toward

prophylaxis are far from homogeneous, the indications de-

pending on factors such as age, presence of reﬂux, grade of

reﬂux, recurrence of infections, and dysfunctional bladder. A

controlled study of patients with reﬂux grade III-IV has been

proposed

The population at risk for scarring and further

Table 1 Frequency of Abnormal “Acute” DMSA in the Case of

Clinical Pyelonephritis: Selection of Large Series of Cases

Authors Year

Percent Abnormal

DMSA

Majd et al

1991 66%

Rosenberg et al

1992 52%

Melis et al

1992 62%

Jakobsson et al

1992 78%

Benador et al

1994 67%

Levtchenko et al

2000 68%

Hoberman et al

1999 61%

Benador et al

2001 65%

A. Piepsz and H.R. Ham

kidney deterioration being the one with DMSA lesions during

acute pyelonephritis, one could hypothetize that DMSA pat-

tern, rather than MCUG, may serve as an indicator for che-

moprophylaxis, which raises the need for a prospective ran-

domized study with and without prophylaxis, patients being

stratiﬁed according to both the DMSA and the MCUG results.

Duration of Follow-up

It has been the merit of some clinicians to have followed

prospectively large cohorts of patients with UTI, to detect any

complication, such as recurrent infections, progressive scar-

ring, or late complications of hypertension or renal fail-

ure.

74-76

The advantages of such prospective follow-up

should be put in balance with the major drawback of keeping

under medical control lots of children who are unlikely to

develop complications. Vernon and coworkers have shown,

on a large population of northern United Kingdom,

that

children older than 4 years of age presenting an acute pyelo-

nephritis without DMSA lesions will not develop any late

scarring, whatever the grade of reﬂux or the recurrence of

infections. Because children younger than 3 years of age are

not more susceptible than older ones for the development of

scars,

78-80

a similar prospective study should be extended to

this young age group. Again, the DMSA scintigraphy, already

performed during the acute phase of infection, could serve as

a criterion for the decision or not of a careful long-term fol-

low-up.

Late DMSA and Scarring

Is it important to diagnose scars? From a recent review of the

literature,

it is obvious that children and adults with pyelo

nephritic renal scarring are at risk of serious long-term com-

plications, such as renal insufﬁciency, hypertension, and

pregnancy-related complications. The interpretation of these

studies is not straightforward. Most of these studies are ret-

rospective and comprise rather small numbers of patients.

Long-term studies

71,82

describe the evolution of young pa

tients diagnosed at a time when medical care was different

from the present one. The results may not represent the risks

of the pediatric population of today. Moreover, it is probable

that the risk at late age could be largely predicted on the basis

of the characteristics at entry: number and size of the renal

lesions, level of overall and single kidney GFR, initial blood

pressure. In a recent Italian multicentric study, for instance, it

has been shown that end-stage renal disease by age 20 years

was 56% when the inclusion criteria were limited to children

with a creatinine clearance below 75 mL/min/1.73 m

Hav

ing this in mind, an accurate approach of morphology and

function of the kidney, at least at entry, is mandatory.

Research

Although a huge literature covers the different aspects of

urinary tract infection, the controversy is still immense in

ﬁelds such as treatment of acute pyelonephritis, indication

for chemoprophylaxis, role of vesico-ureteral reﬂux, scar-

ring, and level of renal function. Local traditions and beliefs

often replace strong evidence. End points should ideally be

the complications at a later age, but the comparison between

early and late DMSA scintigraphy has proven to be an ade-

quate surrogate end point.

60-62

There is a need for well-con

ducted prospective studies using these criteria.

The Renogram

Guidelines

During recent years great effort has been put into better stan-

dardization of the renogram in children. The “well-tempered

diuretic renogram”

was a valuable effort to standardize the

diuretic renogram. The consensus conference

was essen

tially centered on the determination of split function in chil-

dren and adults. The EANM pediatric guidelines

covered all

of the aspects of the renogram, including split function, tran-

sit determination and analysis of the diuretic curve.

Therefore, it is not the purpose of this review to redeﬁne all

the aspects of these guidelines but to emphazie somewhat

more on some aspects of the renographic technique, such as

new developments, or simply controversial points. More-

over, it also is our aim to explore the ﬁeld of application of the

technique, according to the experience of the author and to

analyze how this technique has inﬂuenced the strategy of

management in antenatally detected hydronephrosis.

Interpretation of the Renogram

Since the 1970s, the physiological signiﬁcance of the reno-

gram is well recognized.

Flow, uptake, and excretion are

overlapping within the so-called vascular, parenchymal, and

excretion phases. The practical implication of this overlap is,

however, not always well understood. The time to the max-

imum of the renogram (T

max

) is simply the equilibrium point

between uptake and excretion and not the beginning of the

excretion, which starts earlier. Describing grossly the renal

transit on the basis of empirical parameters such as T

max

is a reasonable approach, but one should be aware of

the fact that the overall level of renal function may consider-

ably affect these empirical parameters. Similarly, a simulta-

neous injection of tracer and furosemide often gives rise to a

curve characterized by a short T

max

followed by a ﬂat third

phase. Such a ﬂat curve does not mean absence of excretion

but an extraction from the blood equal to what has been

excreted. The solutions to these limitations will be evoked in

the paragraph on renal transit.

Tracers

DTPA is the most widely used renal dynamic tracer. It is a

small molecule that is exclusively ﬁltered by the glomeruli

with an extraction efﬁciency of 20%. MAG3 is almost exclu-

sively excreted by secretion in the proximal tubules with an

extraction fraction of approximately 50%.

The main reason

to use this last tracer, or other tracers with high extraction

rate such as Hippuran-I123 or Tc-99m EC, is the high target

to background ratio resulting in good image quality, which is

of particular importance in the infant who has an immature

function. Prenatal screening of hydronephrosis is aimed at

detecting as early as possible alterations of renal function to

assure, from the beginning on, the adequate treatment and/or

follow-up. One cannot expect to determine split function

Pediatric applications of renal nuclear medicine

with high accuracy by means of DTPA in the very ﬁrst

months of life. Improvement of initial low split function or

deterioration of function can both occur within the ﬁrst 6

months of life and may be overlooked on DTPA studies.

Is it Acceptable to Use

MAG3 Split Function to

Estimate Split Glomerular Function?

It has been demonstrated in experimental models that both

tubular and glomerular function are affected differently in

some well-deﬁned conditions. Acute experimental unilateral

total ureteral obstruction gives rise to a glomerular function

more depressed than the tubular function on the side of the

obstruction.

This phenomenon is observed during the ﬁrst

few hours after obstruction, after which tubular and glomer-

ular split function become comparable.

Acute ischemia

provoked by complete ligation of the renal artery results in

similar glomerulo-tubular imbalance.

In clinical practice,

acute obstruction, such as observed in renal colics, gives rise

to the same discrepancy between glomerular and tubular

split function.

92,93

It also is well known that in renovascular

hypertension, the administration of captopril may depress

considerably the glomerular uptake function, without any

effect on tubular uptake. However, there is a large body of

literature conﬁrming that in most nonacute situations in chil-

dren and adults, such as nonrenovascular hypertension, re-

nal insufﬁciency, hydronephrosis, megaureters, small kid-

ney, duplex, both glomerular, and tubular function, are

almost identical,

93-97

justifying the use of tubular tracers with

high extraction for the estimation of glomerular split func-

tion.

Parameters That May Affect the

Determination of Split Function in Children

Drawing Renal ROI

It is essential that renal ROI include the entire parenchyma.

One should be able to modify the window, to enhance the

contrast of the renal image. Moreover, because late accumu-

lation of tracer can occur in the pelvis, one should verify that

the renal ROI, which has been drawn on the ﬁrst images of

the acquisition, still contains the enlarged pelvis, as seen on

the late images.

Drawing Background ROI

Consensus and guidelines

85,86

suggest the perirenal back

ground as the best compromise for the structures overlying

the kidney area. The vascular component is underrepre-

sented when using the popular subrenal area, whereas it is

the tissular component that is underrepresented when using

the liver and spleen area exclusively. It can be shown that, in

a single kidney model, a background ROI located in the

subrenal area of the absent kidney may give rise, in this

absent kidney, to a split function as high as 25% of the total

function

In young infants, very dilated systems may complicate the

drawing of the ROI, the danger being a perirenal ROI par-

tially outside the patient. Adequate zoom should be intro-

duced at acquisition and, if necessary, one should avoid the

external part of the background area.

Algorithms for Split Function

The background corrected count between 1 and 2 min is well

accepted as representing the split function (integral method).

Theoretically, the Rutland-Patlak plot

removes the vascular

part of the background that has not been completely cor-

rected by subtracting the perirenal activity. In the case of

tubular tracers such as MAG3, the inﬂuence of this residual

background activity on split function is negligeable.

100

over, new types of errors may result from basic assumptions

inherent to the Rutland Patlak method: the tissular activity in

the kidney ROI is assumed to be identical to the tissular

activity around the kidney; the heart curve is assumed to

represent the plasma curve; and the statistics on the Rutland-

Patlak are less favorable than in the integral method. It has

been shown that both the day to day reproducibility and the

accuracy of split function are not improved by the additional

use of Rutland-Patlak plot.

100

It is only in the case of low

overall function or when a tracer with low extraction such as

DTPA is used that the additional correction might become

useful.

101

In the case of renal failure, any method aimed to

determine split function is entirely invalid.

Time Interval for the Calculation of Split Function

It is well accepted that renal uptake should be measured

between 1 and 2–2.5 min after tracer injection. However, this

constraint is dependent on the renal transit and the time

necessary for a signiﬁcant escape of tracer out of the kidney.

Because the F0 furosemide test becomes more and more pop-

ular in children,

102,103

the escape out of the kidney, under

inﬂuence of a high urinary ﬂow, may occur more rapidly,

sometimes before 2 min, in particular on the nondilated side.

This factor should be taken into account when deﬁning the

time interval during which the split function should be de-

termined, the risk being an underestimation of split function

on the normal side.

103

Absolute Single Kidney Function

Several algorithms based on renal and heart counts have been

proposed for calculating the absolute function of each kidney

separately and the sum of both kidney functions representing

the overall function.

104-107

The most simple one, and there

fore the most popular one, is the calculation of the ratio

between the renal counts between 1 and 2 min and the in-

jected dose, an abacus that transforms this ratio into a clear-

ance value.

108-111

However, many factors contribute to the

inaccuracy of all these methods, namely the errors of estimat-

ing the true renal and plasma activity, ie, the heart curve is

not a plasma curve,

112

the attenuation resulting from kidney

depth can only be approximated, the nonrenal activity over

the kidney ROI plays a more important role than for deter-

mination of split function. Whichever tracer is used, neglect-

ing the additional vascular background will give rise to im-

portant inaccuracy.

113

These techniques are even less precise

than creatinine-based formulae.

114,115

Plasma sample clear

ances are deﬁnitely more accurately and, therefore, it is not

A. Piepsz and H.R. Ham

surprising that until now no guidelines have been produced

related to gamma camera clearances.

In our opinion, the

combination of a plasma sample method for overall renal

function, associated with a split function obtained from the

renogram, constitutes the most accurate approach for single

kidney function. For older children with conserved overall

function, Tc-99m DTPA can be used for both purposes. In

infants or in case of decreased overall function, the combined

use of Tc-99m MAG3 for split function and Cr-51 EDTA is

preferred. In both options, and in accordance with the glo-

merulotubular balance described previoulsy, the results can

be reasonably expressed as single kidney GFR, in mL/min.

Renal Transit

Much has been written on this subject. We refer the reader to

a recent overview of the literature.

116

In pediatric practice, the

choice of the methodology should be adapted to the ﬁnal

objectives expected. The estimation of renal transit on the

basic renogram is aimed at differentiating those kidneys able

to eliminate adequately the amount of tracer that has been

extracted from the blood pool from those with more or less

delayed excretion, which will necessitate a furosemide prov-

ocation test. It is clear that for this purpose, simple method-

ology is sufﬁcient. A normal, slightly delayed, or consider-

ably delayed T

max

is an empirical semiquantitative parameter

allowing decisions about a furosemide test. A transit delay is

nevertheless not excluded despite a normal T

max

: a simple

inspection of the images and the curves may reveal the insuf-

ﬁcient renal drainage at the end of the basic renogram. The

determination of “true renal transit” by means of any of the

deconvolution techniques offers no obvious advantage in dif-

ferentiating normal from abnormal transit or in separating

simple stasis in a dilated system from a true impairment of

ﬂow. On the contrary, several constraints related to the use of

deconvolution are violated in the case of dilated systems and,

in the case of delayed transit, considerable underestimation

of true renal transit is not excluded because the retention

function has not been fully determined at the end of the

renogram.

116,117

Much effort has been put into the determination of cortical

transit, allowing to avoid the problem of stasis into a dilated

pelvis. Parametric images displaying a pixel-by-pixel time

dimension have been proposed, such as a Tmax, mean time

or mean transit time image

118-120

or factor analysis.

121

None of

these techniques has proven to be superior to the others.

Deconvolution on a predeﬁned “cortical area” assumes that

one knows in advance the exact limit between cortex and

collecting system. Moreover, the additional difﬁculty in chil-

dren with hydronephrosis is that the dilated system often

overlaps considerably the cortical area, masking therefore a

normal cortical transit.

122

Finally, according to Britton, the

cortical transit should theoretically be able to separate those

kidneys with simple dilated uropathy from those with a more

severe type of nephropathy as a consequence of a “true ob-

struction.”

123

However, there is no single article demonstrat

ing that kidneys with impaired cortical transit are at higher

risk for functional deterioration if left untreated.

Furosemide Test

It was the hope, when the furosemide test was introduced

124

that it would be able to separate those kidneys with simple

dilation and impaired transit because of the reservoir effect of

the dilated cavity, from a more severe ﬂow impairment re-

lated to obstruction. This is probably true in many adult cases

with acquired hydronephrosis as a consequence of cancer or

ureteral stones. In these cases, an impairment of renal transit

or a poor response to furosemide undoubtedly reﬂects an

obstructive phenomenon. Since the advent of fetal ultra-

sonography in the late 1970s, and the introduction of the

systematic antenatal screening of hydronephrosis, the clini-

cian is faced with an important population of asymptomatic

infants with dilation of the collecting system. In these pa-

tients, the interpretation of the furosemide test is not neces-

sarily straightforward. Although the different steps of the

acquisition, processing and pitfalls have now been well cir-

cumscribed in guidelines and reviews,

86,125,126

several points

are still controversial or simply ignored, as discussed in the

following subsections.

Hydration, Bladder Catheter, and Postvoiding Views

The European attitude is to maintain the test as a noninvasive

procedure. For that reason, adequate oral hydration is preferred

to intravenous hydration administered before and during the

acquisition. Although bladder back-pressure is known as a fac-

tor that may give rise to a poor response to furosemide, placing

a bladder catheter to avoid the accumulation of urine is not

recommended in most of the cases. It can be replaced, in case

of signiﬁcant retention of tracer at the end of the test, by a late

postvoiding image (Fig. 2) obtained after micturition and

after gravity has facilitated drainage.

122

The time at which this

late image should be performed should be standardized: it is

easy to understand that performing the late image at 24 h

would always give rise to an interpretation of “complete renal

emptying.” The time at which a late image should be per-

formed depends on the clinical indication and the approxi-

mate level of transit time. In the case of hydronephrosis, in

which we expect a prolonged transit time, the ideal time for

the late image should be approximately 50-60 min after

tracer injection.

127

After the end of the furosemide acquisi

tion, small children are maintained in a vertical position in

the arms of the accompanying adult or caregive, and sponta-

neous voiding always occurs within the half an hour preced-

ing the late image. Older children are simply encouraged to

void and to walk during this period. A classical pitfall is to

interpret this late image isolated from the furosemide acqui-

sition. It would then systematically give a false impression of

poor renal emptying on the hydronephrotic side. It is of great

importance to scale this late image using the same maximum

for all 3 acquisitions: basic renogram, furosemide test, and

the late postmicturition image.

Parameters Describing the Furosemide

Curve, Including the Late Postvoiding Image

The T1/2 of the furosemide curve has been recommended as

a parameter of choice to estimate the response to the diuretic,

although the committee responsible for the “well-tempered

Pediatric applications of renal nuclear medicine

diuretic renogram” is aware of the fact that the value of T1/2

depends on the way this parameter is measured on the

curve.

An additional pitfall is the fact that the initial height

of the curve on which the T1/2 is based is dependent on the

amount of tracer that has left the kidney before any diuretic

has been administered. Paradoxically, the more that has left

the kidney before the furosemide injection, the less steep the

diuretic renogram will be (Fig. 3). The same paradox is en-

countered when expressing the residual postvoiding activity

in percentage of the activity present in the kidney when start-

ing the diuretic renogram or at the end of the diuretic acqui-

sition.

128

Finally, it is remarkable that all these criteria used to

deﬁne the renal emptying during a F ⫹ 20 renogram have

simply been transposed to the F0 renogram, without further

validation.

It is therefore understandable that new parameters have

been introduced, allowing a better expression of the amount

having left the kidney or still present in the kidney. Output

Figure 2 A 14-year-old girl who un-

derwent, 8 years before this reno-

gram, a left pyeloplasty because of

pelvi-ureteric junction stenosis. The

MAG3 renogram shows an impaired

transit on the left side (images, curves

and high NORA value at 20 min). A

late gravity- assisted and postmicturi-

tion image reveals a good renal emp-

tying, without additional furosemide

injection.

Figure 3 An 8-year-old boy with left hydronephrosis. Renogram performed under simultaneous injection of MAG3 and

furosemide (F0 test). On the left side, the time to the maximum (T

max

) is reached at 4 min, but the curve remains ﬂat

afterward. This is a pattern often observed in F0 renograms. Images, including the postmicturition view, suggest an

absence of renal emptying. The residual activity on the PM image is 99% of the activity seen on the last image of the

renogram, thus conﬁrming the poor emptying. However, such ﬂat renogram, in opposition with a continuous ascend-

ing curve, means that a great part of the tracer which entered into the kidney has left the kidney. This is reﬂected by the

moderately increased NORA value corresponding to a partial but signiﬁcant renal drainage.

A. Piepsz and H.R. Ham

efﬁciency

129,130

is probably the most robust parameter for

that purpose and describes at each moment of the acquisition

(end of basic renogram, end of furosemide curve, postmic-

turition image) the amount of tracer that has left the kidney in

percentage of what has really been taken by the kidney. Some

drawbacks are inherent to the technique, mainly related to a

properly adjustment of the integral of the heart curve on the

early part of the corrected renogram.

131

As noted previously,

the heart curve is only an approximate estimation of the true

plasma curve, whereas the adjustment remains dependent on

the quality of background correction. A practical simpliﬁca-

tion of this parameter is the use of “NORA” (normalized

residual activity), which is a simple ratio between the activity

at a given time of the acquisition (end of basic renogram, end

of furosemide curve, postmicturition image) and the 1- to

2-min renogram activity.

132

This parameter reﬂects the

amount that remains in the kidney. Both parameters (and

particularly output efﬁciency) have the great advantage to be

less dependent on the level of overall function than the tra-

ditional parameters. When both are applied to a general pop-

ulation of children having undergone the renographic proce-

dure, they are fairly correlated.

133

They can be applied whatever the moment of furosemide

injection and allow the quantitative comparison of 2 succes-

sive tests performed in the same child, one using early furo-

semide injection (F0) and the other the F ⫹ 20. The ﬁnal

result, expressed either as the amount which has left the

kidney (OE) or the amount still present in the kidney

(NORA), will be approximately the same on the late postmic-

turition image using either F0 or F ⫹ 20.

134

Normal values have been suggested on the basis of what

was observed in normal contralateral kidneys.

133

Dilated but

obviously nonobstructed kidneys (postoperative dilation, for

instance) will be often characterized by much more altered

drainage parameters, in the range observed in kidneys highly

suspected of PUJ obstruction.

F ⴙ 20, F0, or F-15?

Early furosemide injection was introduced initially to trans-

form an equivocal F ⫹ 20 curve into either a normal curve or

an obstructive pattern. In pediatric practice, however, as

mentioned previously, the ﬁnal drainage will be, in most

cases, similar at a given time, whatever the moment of furo-

semide injection. The choice of timing for furosemide admin-

istration should be dictated by other reasons. The advantage

of F ⫹ 20 is the possibility of estimating renal drainage on the

basic renogram, in conditions similar to the normal urinary

drainage during the daily life. One has then the choice to give

or not to give the diuretic depending on the shape of the basic

renogram. However, one can expect almost certainly, in case

of a dilated collecting system, to observe poor drainage on the

basic renogram. Therefore, in case the indication of the test is

clear, it might be interesting to administer both the diuretic

and the tracer simultaneously. For those who are in favor of

using ﬁne butterﬂy needles instead of placing a Venﬂon in

small children, this technique permits the avoidance of 2

successive venipunctures. Moreover, it shortens the time of

acquisition on the gamma camera. A theoretical drawback is

the striking change of urinary ﬂow during the course of the

renogram, since the maximal effect of the diuretic will occur

only during the second part of the renogram. For those who

feel uneasy with a procedure implying a dramatic urody-

namic change during the acquisition, the injection of the

diuretic 15 min before the tracer (F-15) will circumvent this

drawback but offers no additional advantage compared with F0.

Interpretation of Drainage

The interpretation of drainage is probably the main pitfall

related to the technique. It is well accepted in the nuclear

medicine world and also by the referring clinicians that an

impaired transit during the basic renogram has no strong

signiﬁcance as far as obstruction is concerned. Any dilation of

the collecting system such as observed in various situations,

such as major reﬂux, extrarenal pelvis, and postoperative

situations, may result in a “reservoir” effect. The furosemide

test is aimed to separate a “lazy” collecting system from real

impairment of urinary ﬂow. Unfortunately, the “reservoir ”

effect may occur even during the furosemide acquisition and

the late postmicturition images. Indeed, despite the increased

urinary ﬂow provoked by the administration of the diuretic,

it might take a long time before the tracer, which has to

occupy the whole dilated cavity, will be able to leave the

kidney in signiﬁcant amounts. The consequence of this vol-

ume effect is that one can probably reasonably exclude an

obstructive phenomenon in case of a good response. Absence

of signiﬁcant drainage can only be described and quantiﬁed

and should not be interpreted as representing true obstruc-

tion (Fig. 4). It has been suggested that this nonresponse to

furosemide attributable to a large volume of the collecting

system is characteristic of the young infant, because of imma-

turity and low renal function in that age group.

135

This is not

the experience of our group. Poor responses to furosemide

were not more frequent during the ﬁrst 6 months of life and

often did not improve at a later age in the absence of any

surgical treatment.

136

Parenchymal Images

The morphological information contained in the early dy-

namic images should not be neglected. Images can be sum-

mated between 1 and 2 min and, using an appropriate gray

scaling, may reveal the presence of a small kidney, regional

areas of dysplasia or scarring such as in duplex kidneys or

dilated reﬂux.

Vesicorenal Reﬂux or Movement Artifact?

Beside the determination of the main quantitative parame-

ters, one should be particularly careful in detecting transitory

vesicorenal reﬂux during the renographic acquisition. It is

not rare that a reﬂux episode can be detected in infants dur-

ing the renogram, either because of a full bladder, or as a

consequence of a spontaneous micturition. Such detection

may spare a young child the aggressive direct cystography

that often is planned in antenatally detected hydronephrosis.

A sudden increase of activity in the late phase of the renogram

is indicative of reﬂux. However, images should be carefully

checked to exclude any movement artifact that could give rise

Pediatric applications of renal nuclear medicine

to the same curve pattern (Fig. 5). Periodic variation in ure-

teral contraction also may cause the curve to increase.

The Renogram in Pediatric Practice

Pelviureteric Junction Stenosis (PUJ)

PUJ is undoubtedly the main indication in the postnatal

period, although not a ﬁrst-line examination. Dilation of

the fetal collecting system is observed in approximately

0.25% of pregnancies

137

and the priority is to detect the

presence of underlying urethral valves, representing a

clinical emergency, or pathologies such as vesico-renal

reﬂux, uretero-hydronephrosis or duplex kidney. Once

these pathologies are excluded, isolated pelvic dilation

will conceivably be the result of PUJ. These neonates with

PUJ are in good health and present no symptoms. The

natural history of this condition, as well as its optimal

management, is still a matter of debate. Strategies of man-

agement are aimed to preserve renal function and to pre-

vent the occurrence of severe infections.

Is Surgery an Emergency? A traditional statement found in

the introductions of a great number of urologic articles over

the past 50 years or more is that “it is important to diagnose

obstruction since obstruction left untreated will lead to loss

of renal function.” This is undoubtedly true in case of total or

subtotal obstruction, such as in urethral valves, in which

obstruction should be relieved immediately. The antenatally

detected PUJ is on the contrary a partial obstruction and does

not represent a surgical emergency. In most of the cases, this

situation, even untreated, will not lead to loss of function.

Numerous experimental studies have been produced to sim-

ulate the clinical model of antenatally detected PUJ. Chevalier

and Klahr

138,139

have demonstrated renal atrophy and apo

ptosis as a consequence of obstruction. However, it is clear

that the models created are subtotal or total obstruction. The

consequences of these types of obstruction do not represent

what is observed in children with PUJ. Josephson, a pioneer

in the experimental approach of this pathology, has shown

long-term preservation of renal function and anatomy de-

spite the created obstruction.

140

The Ulm and Miller’s model

that he used creates a partial obstruction but again might not

necessary mimic the degree of narrowing found in children.

Stratifying the children with PUJ within 2 categories, those

with and those without obstruction, is undoubtedly a too

simplistic way to classify these patients. The degree of partial

obstruction probably lies within a continuum, between slight

and much more pronounced narrowing of the junction. Sev-

eral factors, such as infection and position of the patient, can

modify the degree of obstruction.

Can Obstruction Be Deﬁned at Entry? The size of cavities,

as measured by means of radiological techniques, not only

depends on the degree of narrowing but also on factors such

as compliance of the system and therefore cannot serve as a

marker of obstruction. The pitfalls related to pelvic pressure

measurements are well known. Differential function, as pro-

vided by the renogram, can be abnormally low as a conse-

quence of obstruction, but additional factors such as associ-

ated renal dysplasia may explain an initial low function. Poor

drainage under furosemide can be simply the result of the

reservoir effect of a dilated cavity. Finally, inspection of the

pelviureteral junction during the procedure of pyeloplasty

will conﬁrm, despite the narrowing of the junction, the still

permeable lumen. The only deﬁnition of obstruction on

Figure 4 An 11-year-old girl. Pelvi-ureteric junction stenosis discovered 2 years before this renogram, because of

intermittent loin pain. No surgery was performed, and the child is now asymptomatic. On the MAG3 renogram

performed under furosemide (F0 test), the split function is almost symmetrical, but the drainage is poor, even on the

postmicturition view (NORA PM: 3.0). A poor response on furosemide cannot be considered as a criterion of further

function deterioration.

A. Piepsz and H.R. Ham

which there is an agreement, according to S. Koff, is “any

restriction to urine ﬂow, that left untreated, will cause pro-

gressive renal deterioration.”

141

This is unfortunately a retro

spective diagnosis.

Can Deterioration of Kidney Function and Anatomy Be

Predicted? There are no solid data demonstrating that the

size of the renal cavity, the differential renal function, the

level of pelvic pressure, or the response to furosemide con-

stitute factors of risk for further deterioration. According to

Koff,

141

hydronephrosis might constitute a kind of protection

against the increased pressure as a consequence the narrow-

ing. Noncompliant systems might constitute a factor of risk,

since the elevated pressure will be directly transmitted to the

kidney. The dosage of TGF-beta 1, as a marker of ﬁbrosis and

therefore of noncompliance, is worthwhile to be systemati-

cally evaluated.

What Are the Risks of a Conservative Nonsurgical Atti-

tude? The experimental and clinical work of some pio-

neers

140,142,143

have encourage clinicians to have, in many

circumstances, a conservative approach. Nevertheless, di-

verging opinions still exist and the controversy remains in-

tense around the criteria for surgery and even the principle

itself of no intervention in infants with PUJ.

144

Fear of loss of

function, when the anomaly is known since fetal life, is put

forward. Extensive compilations and critical review of the

extremely heterogeneous literature have been published re-

cently.

126,145,146

The most striking point appearing from these

reviews is the lack of rigorous approach and the total absence

of randomized studies. Results are contradictory but these

studies are not comparable.

Is Expectancy Generally Justiﬁable? As a matter of fact,

overall results are encouraging. According to Josephson’s

compilation,

145,146

90% of 474 neonates allocated to watchful

waiting were not operated. Only 10% were subjected to de-

layed pyeloplasty, mostly because of increase of pelvic size

and/or decreasing differential renal function.

How Often Did Symptoms Occur in Case of Expectancy?

Symptoms

are not frequent. UTI is noted in approximately 5% and is

generally of mild nature. Renal colic seems to occur ex-

tremely rarely.

Does Huge Hydronephrosis Foretell Future Function

Loss? Josephson’s survey

145

showed that half of the expec

tancies had an initial gross hydronephrosis. Nevertheless, in

88% of them, the nonoperative treatment could be carried

through. On the whole, reports of increasing pelvic size were

rare. Thus so far, the presence of a gross hydronephrosis

seems to have a limited prognostic value.

What Is the Risk of Function Loss During Expectancy?

Again, according to Josephson’s compilation,

145,146

expect

ancy was successful in 90% of the cases. Crossover to delayed

Figure 5 A 6-month-old boy with bilateral grade V reﬂux. A 20-min MAG3 renogram was performed under furosemide

stimulation (F0 test). One can identify easily, on both the images and curves (arrows), 2 clear episodes of vesico-renal

reﬂux occurring during spontaneous voiding.

Pediatric applications of renal nuclear medicine

pyeloplasty was decided in approximately 10% of cases, the

reason being either pelvic size increase or deterioration of

differential function. These events mostly occurred during

the ﬁrst 2 years of life.

For those kidneys with an initial differential renal function

(DRF) less than 40%, expectancy led, according to Koff and

coworkers

143

to improvement of function in approximately

70% of cases. In those cases with deterioration of function,

late pyeloplasty, performed without delay, generally restored

the initial DRF values. Early pyeloplasty, in case DRF was less

than 40%, probably did not result in a higher percentage of

cases with restoration of function. Similarly, suddenly unex-

pected complete loss of function has, in our personal experi-

ence, occurred only very rarely during conservative manage-

ment. Complete loss of function, although very rare, also has

occurred after uneventful pyeloplasty, according to our per-

sonal experience with experienced pediatric urologists.

Does Early Surgery Result in Better Preservation of Split

Function Than Late Surgery After the Deterioration of

Function? Patient series from the past are useless for such an

analysis because they constitute a selected group of older and

symptomatic cases. Clear answers can only come from well-

designed prospective randomized studies.

What Are the Long-Term Hazards of a Conservative Ap-

proach? The experience on follow-up of conservatively treated

patients is still limited in time and is not more than 10 to 15

years. In the past, however, when patients were addressed for

PUJ discovered because of symptoms, DRF often was acceptable

or almost normal, suggesting that the effect of symptoms on

function was relatively modest. Long-term follow-up on these

patients is needed to evaluate more precisely the frequency and

consequences of clinical symptoms or the occurrence of com-

plications such as severe tubular disease or stones.

Alternatively, Is Early Surgery the Solution to Avoid Any

Further Complication? The occurrence of clinical complica-

tions is still possible in case of pyeloplasty. Severe and recur-

rent infections caused by multiresistant bacteriae may follow

the surgical procedure. Variable surgical complications are

possible in a minority of cases, from minor events such as

leakage up to complete loss of renal function.

In the Case of a Conservative Approach, How Often Should

Examinations Be Performed? Those in favor of a conserva-

tive approach insist about the necessity of close follow-up,

particularly during the ﬁrst 2 years.

147

Ultrasound is certainly

the instrument of choice to rapidly detect any signiﬁcant

alteration of pelvic size. The information whether one can

rely on repeated ultrasound to decide about performing a

control renogram is still required. In other words, can one

assume an unchanged or improved function on the basis of a

stable or improved hydronephrosis?

Other Clinical Indications

Megaureter. Like for PUJ stenosis, a conservative approach

often is recommended, whether or not the megaureter is asso-

ciated to hydronephrosis and/or vesicorenal reﬂux. The role of

the renographic study is to verify the quality of the underlying

renal function and to asses the quality of renal and ureteral

drainage, since the clinical question may be to differentiate a

reﬂuxing megaureter from an obstructive one because of vesico-

ureteral stenosis. The furosemide test (F0 or F ⫹ 20) may give

rise to the same uncertainty as for hydronephrosis. Good ure-

teral emptying on the late postmicturition image almost ex-

cludes the diagnosis of obstructive megaureter, while an impor-

tant ureteral stasis can simply reﬂect the additional effect of a

slow ureteral transit related to the enlarged reservoir and of a

continuous input from the kidney.

Duplex Kidney. Although many duplex kidneys simply con-

stitute normal variants, pathological duplex kidneys can give

rise to clinical complications. Dysplastic moieties, ureteroco-

ele, hydronephrosis, reﬂux, and obstruction may all lead to

associated recurrent infections or pyonephrosis. Split func-

tion in case of normal duplex may be signiﬁcantly out of the

accepted 45% to 55% normal range. In case of pathological

moiety, it has been shown that split function remains un-

changed at follow-up during conservative management.

148

When deciding about a partial nephrectomy, the surgeon

may be interested in evaluating the remaining function of the

pathological moiety. In case of very low remaining function,

the quantitative estimation is imprecise and one may proba-

bly better rely on the appearance or not of some renal activity

on the late images to decide whether the function of this

moiety is low or completely absent.

Horseshoe Kidney. It is not rare that the diagnosis of horse-

shoe kidney is made during the renographic procedure and

has been missed on previous radiograph examinations. A

diuretic challenge may be indicated in case of associated hy-

dronephrosis due to vascular compression.

Small and Dysplastic Kidneys. Follow-up of split function is

aimed to evaluate the long-term the outcome of both the

normal and the abnormal kidney. It has been shown that in

most of the cases split function remains unchanged for years,

reﬂecting an equal maturation of the normal and the abnor-

mal kidney.

149

Ectopic Kidney. The precise determination of split function

in case of pelvic kidney is hampered by the anterior displace-

ment of this kidney not allowing an exact functional estima-

tion. One simple way to correct, at least partially, for kidney

depth using a single head gamma camera, is to perform at the

end of the acquisition an anterior and poasterior view and to

determine, for each kidney separately, the number of counts

in posterior alone and using the geometric mean. The ratio of

both values is then used to correct the number of counts

obtained during the renographic acquisition. One should be

aware however that the attenuation due to the pelvic bone

structure is still not corrected and gives rise to a signiﬁcant

underestimation of the function in the ectopic kidney.

Place for Absolute Individual Kidney Function Determina-

tion. In some clinical conditions, the split function is unable

to assess the quality of the individual kidney function. This is

A. Piepsz and H.R. Ham

obvious, for instance, in case of single kidney or bilateral

disease. In these cases, the combination of split function with

an overall clearance by means of plasma samples (DTPA or

EDTA) can be extremely helpful. As an example, it can clarify

in some cases the ongoing controversy related to the su-

pranormal function sometimes observed in antenatally de-

tected hydronephrosis. As a matter of fact, it has been

shown

150

that the abnormal high split function on the hydro

nephrotic kidney side may be simply the result of a low

absolute function on the contralateral side, which was con-

sidered as structurally normal. Expressed in absolute func-

tion (ml/min), the function on the hydronephrotic side was

in the normal range.

An unchanged split function generally is associated with a

bilateral maturation of the individual absolute renal func-

tion.

148,149,151

A decreasing split function may still corre

spond to some functional maturation, although less pro-

nounced than on the contralateral side.

The intensity of contralateral functional compensation can

be precisely estimated and it is interesting to note that this

compensation only occurs when the split function of the

pathological kidney is less than 30%.

152

On a fundamental

point of view, it is also interesting to note that in the case of

asymmetrical function observed during the very ﬁrst months

of life, one would expect that the less-functioning kidney is

using its functional reserve maximally and therefore not able

to develop the same rate of maturation as on the contralateral

side. In practice, and at least during the ﬁrst two years of life,

the maturation occurs symmetrically in both kidneys, result-

ing in an unchanged split function.

149

Radionuclide Cystography

Techniques

Methods for both direct and indirect radionuclide (RN) cys-

tography have been described elsewhere in detail.

153,154

Both

techniques have advantages and disadvantages, compared

with the classical radiological micturating cystourethrogra-

phy (MCUG) and are summarized in Table 2.

The radiological technique is still widely used and remains

the reference technique for most of the urologists. It allows

the detection of morphological abnormalities such as dupli-

cated ureters, urethral valves, and ureterocoele. Moreover,

the international grading system is now universally ap-

plied

155

and characterizes the intensity of reﬂux. However,

reﬂux may be only intermittent and, for that reason, transient

intense reﬂux may be completely missed. Placing a bladder

catheter is an invasive procedure, in most of the cases poorly

tolerated by the child and may give rise, despite all precau-

tions, to severe iatrogenic pyelonephritis. The radiation bur-

den is considerable.

Direct RN cystography is based on the same principle as

MCUG and its invasiveness is identical. The bladder is pro-

gressively ﬁlled through a bladder catheter and both the ﬁll-

ing phase and the voiding phase are entirely recorded. The

sensitivity in detecting reﬂux is therefore higher than with

MCUG. It can, like for MCUG, be applied to children of any

age, since the active collaboration of the child is not neces-

sary. The radiation burden is low. The technique has how-

ever not gained wide acceptance in the world. One reason for

that is the poor resolution of the images, not providing any

morphological information about the lower urinary tract.

The second one is the fact that the urologist is familiar with

the radiological grading system and the capacity to distin-

guish dilated from nondilated systems. The third one is prob-

ably the rather long occupation time of the gamma camera

and the fact that many nuclear medicine physicians are not

familiarized with the technique.

Indirect RN cystography comes as a complement to the

renogram. At the end of the renogram, the tracer generally

has left the kidneys and is ﬁlling the bladder. The child who

wishes to void can then be asked to void in front of the

gamma camera, thus allowing the visualization of active re-

ﬂux. It is recommended to use a tracer with high extraction

rate, such as Tc-99m MAG3. Unsatisfactory results are ob-

tained with Tc-99m DTPA because of the increased residual

renal activity. The technique, contrary to the 2 other ones, is

not invasive and does not require a bladder catheter. The

radiation burden is low and the technique offers the advan-

tage of providing additional renal functional information ob-

tained from the renogram. Unfortunately, the technique can

only be applied to children older than 3 years of age, who are

able to void on command, whereas most of the ﬁrst UTIs

occur before 2 years of age. Moreover, because of the incom-

plete bladder ﬁlling, the technique is much less sensitive than

the direct techniques.

156

However, opinions diverge and

some authors consider even the indirect technique as the

most sensitive one. This generally is the case when the criteria

for reﬂux are based on some debatable quantitative aspects,

such as for instance a ureteral activity higher than three stan-

dard deviations of the ureteral background.

157,158

Which Technique for Which Strategy?

Morphology of the Lower Urinary Tract

Precise information on urethral valves, ureterocoele, bladder

diverticules, and duplicated ureters, which may inﬂuence the

diagnosis and the further management, cannot be obtained

by means of radionuclide cystography.

Table 2 Advantages and Disadvantages of Direct and Indirect

Cystography

Advantages Disadvantages

MCUG Morphology High radiation burden

Grading

Any age

Snaps shots, resulting

in low sensitivity

Invasive (bladder

catheter)

Direct RN High sensitivity

Filling and voiding

Any age

Low radiation burden

Invasive (bladder

catheter)

No grading, no

morphological data

Indirect RN Noninvasive Partial bladder ﬁlling

Low radiation burden Low sensitivity

Information about

renal function

Only in patients older

than 3 years of age

Pediatric applications of renal nuclear medicine

Grading of Reﬂux

The urologist is familiar with the radiological MCUG Inter-

national Grading System. It is clear, however, that direct RN

cystography can tell the surgeon whether or not the reﬂux is

reaching the kidney (corresponding at least to a radiological

grade II reﬂux), if the reﬂux within the kidney is moderate or

intense, intermittent or continuous, if it appears at low blad-

der ﬁlling or only at the end of the ﬁlling, or if the reﬂux is

passive or active. Some degree of quantitation also is possible.

Control of the Presence of Reﬂux

Once the reﬂux is diagnosed, any further control of the pres-

ence of reﬂux, either during conservative treatment or after a

surgical procedure, should be obtained by means of RN di-

rect cystography because of the higher sensitivity and the

much lower radiation burden.

Direct or Indirect RN Cystography?

This is still a matter of debate. If the information needed for

further management is to know whether the reﬂux is still

present and important, those in favor of the direct technique

will consider the high sensitivity and the fact that it can be

applied whatever the age. High-grade reﬂux can be observed

on direct cystography, associated with severe cortical dam-

age, whereas the indirect cystography is negative.

156

Those in

favor of the indirect technique raise the point that both tech-

niques can miss a similar number of signiﬁcant reﬂux.

159

They consider that the intense bladder ﬁlling during direct

cystography does not reﬂect the natural bladder ﬁlling in the

daily life and may create artiﬁcial reﬂux, not necessarily

linked to any signiﬁcant clinical picture. Owing to the non-

invasive character of the indirect cystography, it is reasonable

to recommend this technique in children older than 3 years

of age. In case of negative result, an additional direct cystog-

raphy is mandatory to exclude with high conﬁdence the pres-

ence of signiﬁcant reﬂux. The cost-beneﬁt of this double

procedure should then be evaluated for each particular case.

Is It Necessary to Check for

Reﬂux in Each Case of Acute UTI?

Traditionally, the detection of reﬂux by means of cystography

is recommended in any case of complicated urinary tract

infection. For some authors, it is even the only imaging tech-

nique which makes sense in this context.

However, recent

work tends to indicate that the presence or not of a renal

lesion may represent the key for deciding about cystography

studies.

This strategy would spare a great number of unnec

essary invasive examinations.

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