Renal Enlargement in Children with Acute Pyelonephritis and. Time Needed for Resolution: Implications for Renal Growth Assessment. Frederick. E. Pickworth1.
405
Sonographic Measurement of Renal Enlargement in Children with Acute Pyelonephritis and Time Needed for Resolution: Implications
Frederick
E. Pickworth1 John B. Carlin2 Michael R. Ditchfield1 Margaret P. de Campo1 John F. de Campo1 David J. Cook1 Terry Nolan3 Harley R. Powell4 Robert Sloane3 Keith Gnimwood3
accepted
2Department of Clinical statistics, Royal Children’s Victoria 3052, Australia.
Victoria to J. F.
Epidemiology and BioHospital, Melbourne,
3Department of Paediatrics, Royal Children’s Hospital, Melbourne, Victoria 3052, Australia. 4Department of Nephrology, Royal Children’s Hospital, Melbourne, Victoria 3052, Australia. 0361 -803X/95/i
© American
652-405
Roentgen
Ray Society
Assessment
1995;165:405-408
for publica-
Presented at the annual meeting of the Royal College of Radiologists, Norwich, U.K., September 1994. 1 Department of Radiology, Royal Children’s Hospital, Flemington Rd., Melbourne, 3052, Australia. Address correspondence deCampo.
Growth
OBJECTIVE. Failure of a kidney to grow satisfactorily in childhood is evidence of renal disease. Because kidneys may enlarge during an episode of acute pyelonephritis, concomitant renal length measurements cannot be used as baselines for growth assessment. This study was designed to determine the degree of renal enlargement in children with acute pyelonephritis and the time the enlargement takes to resolve after treatment is started to find the optimum time for obtaining baseline measurements. SUBJECTS AND METHODS. In a cohort study, 180 children younger than 5 years old with their first proven acute urinary tract infection, with or without pyelonephritis, had renal scintigraphy and sonography within 1 5 days of starting treatment. The presence of cortical defects on scintigrams indicated pyelonephritis. The lengths of kidneys with and without scintigraphic defects (i.e., with and without pyelonephritis) were compared, adjusting for age and sex, and the length of kidneys with defects was related to time elapsed between the start of treatment and sonography. RESULTS. Ninety-nine kidneys (28%) in 77 children (43%) had scintigraphic defects. Kidneys with defects were an average of 3.2 mm longer than kidneys without defects. Length and time interval between treatment and sonography in kidneys with defects correlated negatively, with mean length approaching that of kidneys without defects by 1 0-11 days. CONCLUSION. Kidneys with acute pyelonephritis initially increase in length but return to normal on average by the 11th day of treatment. If poor renal growth is used as an indication of renal disease, sonography should be delayed or repeated at least 2 weeks after the start of treatment to determine the length of the uninflamed kidney. AJR
Received June 27, 1994; tion March 28, 1995.
for Renal
Failure of a kidney to grow at a satisfactory rate in childhood is evidence of renal disease. In children with urinary tract infections, initial renal sonognaphic examinations are used to detect surgically correctable abnormalities and preexisting scanring. The initial sonognaphic examination also gives a baseline measurement of renal length, against which future renal growth can be judged. Previous studies using excretory unognaphy and sonognaphic measurements have shown that vanable enlargement of the kidney occurs in patients with acute pyelonephnitis [1-6]. Subsequent measurements in such patients will thus give an erroneous impression of poor renal growth if the initial sonognaphic measurements are used as baselines. The purpose of this study was to determine the degree of renal enlargement in children with acute pyelonephnitis and to find the time that this enlargement takes to resolve after treatment. This allowed us to predict the optimum time for obtaining baseline renal length measurements after urinary tract infection in children to prevent the overdiagnosis of neflux-associated nephnopathy.
PICKWORTH
406
Subjects
and
This
of 180 children
of ambulant
nary
tract
who
were
children
infection,
with
referred
for
Fifty-eight
1992. crossed,
sonographic
ectopic
growth
of urine
milliliter
from
All
within
15 days
colony
type
evidence
Six coronal, were and
Acuson
used
with
array
[8]
on
Starcam
with
fied
and
Multiple the
normal
increase
groups,
significantly
group
and
or definite
added
to the
used
to
in the
ship
of
renal
displayed
length
using
either
sion
plot
[10].
from
the
regression
cubic
powers
from
the
ables.
effects
Without
modified
regressions
elapsed mean
Computations of the
SAS
fidence
and
on
of were
kidneys 1000
modification,
this
for
1995
on the on using
1 5 months,
to
performed [ii]. the returned
mean
using
A bootstrap time
at
which
to normal samples
from
the
independent length
a con-
length
percentile unique
to
procedure
to obtain
kidney 180
and
scaling.
MIXED used
mixed-
adjusting
in the method,
subjects).
Data Time
Elapsed
Between
Normala
Sex (% female) Age (months) Scmntigraphy
(days
Unilateralb
Bilateralc
(n=103)
(n=55)
(n=22)
55
56
68
17.2
13.4
10.9
12e
6.3
5.8
5.6
41e
5.7
4.9
4.5
.19e
0.7
0.9
1 .0
54d
since beginning treament)
van-
from
of renal
the
and
residuals
interpretable
mean our
residuals
quadratic
residuals,
PROC
(using
regres-
the
residuals
was
was
of Patient
Group
Variable
a sepagroup
against
an
TABLE 1 : Summary Treamtent Stages
The relation-
display
value
the [12]
a
sonography
or partial
same
to the
provide
with
(allowing
(including
Seventy-seven children (43%) had kidneys with scintigraphic defects. Fifty-five of these had unilateral disease, and 22 had bilateral disease, giving a total of 99 (28%) of 350 kidneys with scintignaphic defects. We found no significant difference in the age distribution (p = .12) or in the time interval from treatment to sonognaphy (p = .19) between patients with no disease, unilatenal disease, or bilateral disease. Table 1 summarizes the data for the three groups. Seventy-three percent of the scintignaphic studies were done the same day as the sonographic examinations, 82% within 1 day, and 95% within 4 days. An initial analysis compared renal length between the two groups adjusting for age and sex with mixed-effects analysis of covaniance. A significant increase in renal length was seen in the scintigraphically abnormal group, with an adjusted mean difference of 3.2 mm (95% confidence interval, 2.1 mm, 4.4 mm; p < .001 ; Fig. 1). The same absolute increase in renal length occurred at all ages. For younger patients, this represents a greaten percentage increase. A further analysis examined the effect of time between treatment and sonography, adjusting for age, and found a significant negative comelation in the abnormal group (p = .003; Fig. 2). No significant association was found in the normal group (p = .5). From the regression analysis, the mean difference immediately after the start of treatment was 6.2 mm, reducing to 3.3 mm at 4.8 days (average time to sonography), and then to 0 mm at 10.3 days (the crossover point of the two lines in Fig. 2). The true time after the start of treatment at which the mean length of the kidneys in the abnormal group approaches that in the normal group may be longer than 10.3 days, because the inclusion of scarred kidneys in the abnormal group may have depressed the intercept. Figure 2 shows that considerable statistical uncertainty and substantial individual variability surround any estimate of this time; a bootstrap 90% confidence interval extended from 7.9 to 1 5.0 days.
was
abnor-
length
abnormal
group
is based
bootstrap
August
exam[9] and
before
would
elapsed the
in
length
relationship of renal for each individual to
variables
on age
group
than
any
normal
of renal
of time
adding
of
model
and
whether
sonographic
the
in the
added
abnormal
classi-
of covaniance
version the
program
interval
defective
elapsed
length
classified
group
and normal groups).
for curvature)
Kid-
were
determine
elapsed
a modified
and
for age
time
were
relationship
regression
of renal
to allow
regression
Our
time
to
no
(3) defect.
abnormal
dependence
for the abnormal
plane.
showed
or scarred).
Time
mixed-effects
rate relationship
they
defects
analysis
correlations.
measure-
in any
on scintigrams
treatment
age
by
respectively, length
(2),
mean renal length between for the
independently
whether
the
between
Electric
collimation.
to
were
assess
linscm-
tomography
recorded
pyelonephnitic
mixed-effects
adjusting
with
or definite
greater to
elapsed
infraperson
was
based
seen
units and
(General
Renal
polynomial to represent the nonlinear to age and including a random effect
model
the
results.
(Bothwell,
sector
physician,
measurement
methods
was
used to compare mal
as
of each
UM8
99mTcDMSA
evaluated
medicine
probable
either
In particular,
cubic length
corti-
taken
sonography
high-resolution
according
with
(i.e.,
to time
nation.
was
7.5-MHz and
were
defects
those
regression
length
of acute
technique
(1 ), probable
no or possible
CA)
and
with
imaging
length
graded
as abnormal
renal
or within
sonograms
camera
a nuclear
longest
were
normal,
per
[7].
ATL
gamma WI)
of prior
the
transverse
a standard
scmntigrams and
(0) or a possible
neys as
aspi-
organisms
findings,
99mTcgluconate
400ACT
and
knowledge
defect
suprapubic
presence
View,
using
radiologists
Scmntigrams
The
of 5-MHz
Milwaukee,
All sonograms
were
were
99mTcgluconate
clinical
(Mountain
The
Systems,
ments
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kidneys
scintigraphy
protocol.
128XP
obtained
without
or
undergo
treatment
1 05 urine
a standard
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were
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from than
either
than
and three
with
a GE
Medical
June
pyelonephnitis.
transducers.
tigrams
and
treatment.
six sagittal,
were
not
duplex
(99mTcDMSA)
rather
obtained
WA)
and
solitary
did
of starting
or midstream
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of acute
who
of greater
sonography antibiotic
1990
with
of organism
counts
on scintigrams,
of pyelonephnitis,
Patients
or
un-
Urinary tract infection was diagnosed
specimen
had
of starting
cal defects
ear
1 5 days
cohort
proven
February
patients
hydronephrotic,
99mTcdimercaptosuccinic
kidney
and
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evidence
female.
kidneys
a catheter
patients
clinical
were
of a single
and
5 years
between
from further analysis.
by finding rates
or without
Obstructed,
excluded
than
imaging
examination
excluded.
forms part of a prospective
younger
percent
fused
AJR:i65,
Results
Methods
analysis
study
ET AL.
Sonography
(days
since beginning treatment) Scintigraphy sonography
to (days)
without scintigraphic defects (grades 0-i). bpatients with one kidney with scintigraphic defects (grades 2-3). CPatients with both kidneys with scintigraphic defects (grades 2-3). dchisquare test. eoneway analysis of variance. apatients
#{149}61e
AJR:i65,
August
SONOGRAPHY
1995
OF RENAL
90
80 E E
I
::
50
40 12
24
36
48
Age (months)
Fig. 1 .-Scatter plot of renal length measured on sonograms versus age for kidneys with and wIthout defects shown on scintigrams. Curved lines represent cubic model used In analysis of covarlance calculations. Because curves are parallel, there is a similar absolute Increase in renal length at all ages.
80
75 ..
60,
Ce
70 .c
C a,
65
60 0
2
4 Time to sonography
8 (days),
10
12
age-adjusted
Fig. 2.-Scatter plot of renal length measured on sonograms versus time interval between start of treatment and sonographic examination in abnormal group (both variables adjusted for age). Line of regression (from mixed-effects model) for abnormal group (solid line) and mean 1evel for normal group (dashed line) are superimposed.
Discussion
Previous studies of renal enlargement during acute pyelonephnitis had significant drawbacks: using urognaphy to measure renal size is subject to error from geometrical factors and
ENLARGEMENT
407
possible renal enlargement due to the osmotic effects of contrast material [13, 14]. Using sonography to measure renal length avoids these problems. Previous studies have relied on the clinical and laboratory diagnosis of pyelonephnitis. The clinical differentiation between cystitis and pyelonephnitis in children is unreliable, as is the distinction between unilateral and bilateral involvement [7, 15-17]. Our study differs from previous studies mainly in the method of diagnosing pyelonephnitis. A 99mTcDMSA or 99mTcgluconate scan of the renal cortex obtained during the acute phase will show areas of diminished radionuclide uptake in kidneys with pyelonephnitis and can discriminate between upper and lower urinary tract infections and between unilateral and bilateral pyelonephnitis [8, 18, 19]. These techniques enabled us to compare renal lengths on an individual kidney basis, rather than from patient to patient, and therefore to quantify the degree of renal enlargement more precisely than was previously possible. Two previous studies used sonognaphy to measure renal volume in children with clinically diagnosed acute pyelonephnitis [4, 5]. Dinkel et al. [4] found an average increase in renal volume of 176% in 51 patients compared with control subjects, and Johansson et al. [5] found an average increase of 150% in 47 patients compared with control subjects. These figures may be underestimates; both kidneys were included in their calculations because the clinical distinction between bilateral and unilateral involvement was not possible. Followup sonognams in 29 patients in the study by Dinkel et al. [4] showed a reduction in kidney volume of 50-60% within 2 weeks. Similarly, Johansson et al. [5] showed the most prominent decrease in renal size to occur in the first 2 weeks in the 32 patients who had follow-up sonognaphy. Both studies showed more marked renal enlargement in younger children, who also had more frequent bilateral renal enlargement. A difference in sex distribution between the two groups in our study could have had a confounding effect on renal size, because girls usually have smaller kidneys than do boys. Because some acute defects seen on scintignams can be expected to resolve, any undue delay between treatment and the scmntigraphic examination could give a false-negative result (i.e., the kidney could be wrongly classified as not having had acute pyelonephnitis). If, aftentreatment, the sonognaphy of such a kidney were done before the scmntigraphic study, when the kidney was still acutely swollen, then such a false-negative classif ication would increase the size average in the normal group. Similarly, a delay between treatment and sonography might decrease the size average in the abnormal group. The interpretation of the analysis of the relationship between renal length and time from the start of treatment to sonography assumes that the time of sonography was truly random and not influenced by clinical circumstances, such as severity of illness, which might in turn be related to the degree of renal swelling. This assumption is supported by the comparison of time to sonognaphy between patients who had bilateral disease (and therefore more severe illness) and those who had unilateral disease, which did not show any significant difference. The present study found that, after adjustment for age and sex, there was a mean length difference of 3.2 mm between
PICKWORTH
408
ET
AL.
the abnormal and normal kidneys. This may be considered to lie within the bounds of measurement error and therefore to be of no clinical significance [20, 21]. Such a difference in length, however, represents 4-6 months of growth below 2 years of age and 8-il months of growth between 2 and 5 years of age. It represents a 29% increase between the scmntigraphically normal and abnormal groups in the proportion of kidneys that had renal lengths above the 95th percentile for age. Funthermore, the difference of 3.2 mm represents an average between patients who were examined early, when the kidneys were most swollen, and those examined late, when the swelling had largely subsided. The mean difference just after the time of starting treatment of 6.2 mm is equivalent to 8-li months of growth below 2 years of age, and 17-21 months of growth between 2 and 5 years of age. Similar scintigraphic defects may also be seen in scarred kidneys, and because scanned kidneys may be small, their inclusion tends to reduce the overall length of the kidneys in the abnormal group. Had we been able to perform sonognaphy on all children on the first day of their treatment and been able to exclude all previously scanned kidneys, the mean difference between the two groups might have been considerably greaten than 3.2 mm. Our results indicate that the degree of renal swelling in acute pyelonephnitis can cause a significant increase in renal length, which on average returns to normal within ii days of starting treatment. This effect is greater in percentage terms in younger children. We conclude from these data that, if slow renal growth is to be used as an indication of renal disease, the initial sonognaphic examination of children with urinary tract infections should be delayed until at least 2 weeks of adequate thenapy has been given, to determine the length of the uninf lamed kidneys. Alternatively, if the sonographic examination has already been performed, itshould be repeated after at least 2 weeks of therapy, unless no evidence of pyelonephnitis is seen on cortical scintignams obtained at the time of the acute episode. Such an imaging policy will prevent the ovendiagnosis of reflux-associated nephropathy and the associated prolonged follow-up, with repeated sonography, that these children require to show that the kidney is growing satisfactorily.
REFERENCES
ACKNOWLEDGMENTS
20.
We thank Susan Cahill for assistance management assistance.
of patient
data
and
Patty
in the Chondros
initial for
gathering programming
and
AJR:i65,
August
1995
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J Urol1988;i40:1i69-1i74 Sargent MA, Wilson BPM. Observer variability in the sonographic surement of renal length in childhood. Clin Radioll992;46:344-347 Schlesinger AE, Hernandez RJ, Zenin JM, Marks TI, Klesch RC. observer and intra-observer variations in sonographic renal length surements in children. AJR 1991 ; 156:1029-1032
meaIntermea-