AJR 2005; 184:1630-1633
© American Roentgen Ray Society
High-Resolution Renal Sonography in Children with Autosomal Recessive Polycystic Kidney Disease
Jeffrey Traubici1 and
Alan Daneman
1 Both authors: Department of Diagnostic Imaging, The Hospital for Sick
Children, The University of Toronto, 555 University Ave., Toronto, Ontario M5S
1A1, Canada.
Received April 11, 2004;
accepted after revision August 17, 2004.
Address correspondence to J. Traubici
(jeff.traubici{at}utoronto.ca).
Abstract
OBJECTIVE. Our objective was to describe the spectrum of renal
findings using a high-frequency linear array transducer in patients with
autosomal recessive polycystic kidney disease (ARPKD).
CONCLUSION. There is a spectrum of findings in the kidney in
patients with ARPKD that is very well depicted using the high-resolution
technique described in this article.
Introduction
Autosomal recessive polycystic kidney disease (ARPKD) is an entity well
known to pediatric radiologists who see its variable clinical presentations
and radiologic manifestations. It is a disease primarily of ectatic tubules
and fibrosis. The seminal work by Osathanondh and Potter
[1] described this
"saccular and cylindric increase in size" of the collecting
tubules. Previously termed infantile polycystic kidney disease, it is a
hereditary form of cystic kidney disease that has an estimated incidence of
one in 20,000 live births and a heterozygous carrier state of approximately
one in 70 [2]. The first
reports of the sonographic appearance in ARPKD are case reports from the 1970s
[3]. These were followed by
series in the 1980s and 1990s
[4,
5]. Thus far, however, the
series have been small, and most have not used the newer generation sonography
equipment and high-resolution linear array transducers. We believe that our
series is the largest to date in the radiology literature.
Working from the premise that the affected portion of the nephron in ARPKD
is the collecting tubule, we developed a high-resolution technique of imaging
patients with this disease. This technique relies heavily on the
high-resolution images of very small sections of the kidney obtained with
linear array transducers. Features that might not be seen with a curved array
transducer can be seen with this technique. We think that this technique
facilitates the visualization of sonographic findings that can be useful in
the diagnosis of patients with ARPKD.
Materials and Methods
Thirty-four children with ARPKD have been followed at our institution over
the last 10 years. The diagnostic criteria on which the diagnosis of ARPKD was
made were clinical and laboratory findings consistent with ARPKD, including
renal and hepatic dysfunction; findings on sonography that showed previously
described appearances of ARPKD; normal renal function and normal sonographic
findings in both parents; histologic confirmation at renal biopsy,
nephrectomy, and autopsy; or a family history of the disease in a sibling.
Pathologic confirmation of diagnosis was available in eight patients. Three
had nephrectomies before transplantation. The remaining five had the diagnosis
confirmed either via liver or kidney biopsy or at autopsy.
In 26 patients, high-resolution sonographic images, obtained using the
technique we will describe, were available for review, and these patients
constituted our study population. There were 14 boys and 12 girls who ranged
in age from 1 day to 14 years. The mean age at diagnosis was 3.1 years. The
studies were reviewed by two pediatric radiologists who came to a consensus on
each observation.
Due to the length of the study period, the examinations were performed on
various sonography systems. All of the recent studies, including those
illustrated in this article, were obtained on either an HDI 3000 or 5000 (ATL)
or a Sequoia (Acuson), using a variety of linear array transducers with
frequencies ranging from 8 to 15 MHz.
All examinations were clinically indicated either as part of the workup for
renal failure or for suspected inherited renal disease because of an affected
sibling or as part of the follow-up of a patient with known ARPKD. Standard
examinations were performed assessing the kidneys with both curved array and
linear array transducers. For the high-resolution portion of the study, the
patients were placed in the prone position. If possible, the images were
obtained with suspended breathing. If the patient was unable to cooperate with
breathing instructions, the images were obtained during quiet breathing. A
single renal lobule or a few adjacent lobules were magnified to fill the
screen, and appropriate focal zones applied depending on which portion of the
lobule was being interrogated. The transducer frequency chosen was one that
afforded the best spatial resolution and at the same time penetrated to the
necessary depth.
The criteria that were assessed included dilated tubules, macroscopic
cysts, a preserved cortical rim, and hyperechoic foci with or without
ring-down artifact. Dilated tubules were defined as anechoic structures having
a tubular configuration and often an orientation in either a radial or
parallel pattern. Macroscopic cysts were defined as round anechoic structures
and were differentiated by their shape from dilated tubules. For the purposes
of this article, we defined any cysts that could be resolved sonographically
as macrocysts. An apparently preserved cortical rim was defined as a region of
renal cortex with normal echogenicity and none of the other typical findings
of ARPKD. Hyperechoic foci were defined as punctate areas of increased
echogenicity but without posterior acoustic shadowing. Ring-down artifact from
these foci was also assessed.
Results
Twenty-six patients met our criteria for inclusion. Of these 26 patients,
13 had normal renal function and 13 had abnormal renal function as of their
last sonographic examination. Three patients had undergone renal
transplantation. One had undergone liver transplantation, and one had
undergone combined liver and kidney transplantation. Three patients in our
cohort required dialysis; however, none had sonographic studies performed
while on dialysis or after that. Only one patient included in this cohort died
during the study period. This patient died at 9 years due to sepsis from
gram-negative enterocolitis.
Dilated Tubules
Dilated tubules were seen in 20 patients (Fig.
1A,
1B). The orientation was often
radial to the kidney as a whole, and they were often noted to lie in parallel
columns.
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Fig. 1A. —12-year-old girl with autosomal recessive polycystic kidney
disease. Longitudinal sonogram obtained in lower pole of left kidney using
high-frequency linear array transducer shows diffuse pattern of dilated
tubules (arrows).
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Fig. 1B. —12-year-old girl with autosomal recessive polycystic kidney
disease. Sonogram of entire kidney obtained using curved array transducer
resolves small hypoechoic structures although not to same degree as linear
array transducer.
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Macroscopic Cysts
Macroscopic cysts were seen in 23 patients. In some cases, they were
solitary and, in others, multiple (Fig.
2A,
2B). The cysts were seen in
both the cortex and medulla. In two patients, cysts were seen along the
subcapsular portion of the kidney in a string-of-pearls configuration.
Preserved Cortical Rim
A preserved cortical rim was seen in 10 patients
(Fig. 3). The remainder of
patients displayed one of the other imaging features in the periphery of the
kidney.
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Fig. 3. —4-year-old boy with autosomal recessive polycystic kidney
disease. Longitudinal sonogram of right kidney shows punctate foci of
increased echogenicity and dilated tubules but relatively preserved cortical
rim of tissue.
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Hyperechoic Foci
Hyperechoic foci were seen in 16 patients
(Fig. 4). None displayed a
distal acoustic shadow. In nine cases, the hyperechoic foci were found to be
associated with a ring-down artifact. In the other cases, they were without
any ring-down artifact.
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Fig. 4. —7-year-old girl with autosomal recessive polycystic kidney
disease. Longitudinal sonogram shows multiple punctate foci of increased
echogenicity, with some exhibiting ring-down artifact.
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Discussion
The inherited polycystic kidney diseases have been recognized as distinct
diseases for some time, with historical references going back to the
15th century [6]. It
has been in the last decade, however, that great strides have been made in
understanding the genetics of these diseases. In the mid 1990s, two genes were
identified, PKD 1 and PKD 2 that, when mutated, result in what is referred to
as "autosomal dominant polycystic kidney disease," or ADPKD.
Similar strides have been made in research into ARPKD, and in 2002, Ward et
al. reported the discovery of the gene responsible for ARPKD
[7].
ARPKD is the most common heritable renal cystic disease to manifest itself
in childhood. Sonography has been applied to the diagnosis and follow-up of
children with suspected ARPKD for over 2 decades now. Recent advances in
sonography technology, particularly the improvement in high-resolution linear
transducers, allow resolution of very small structures. Because the
abnormality in ARPKD affects the renal tubule, high-resolution sonographic
techniques are well suited to the imaging of this disease. We have attempted
in our study to exploit these technologic advances to show the changes in
ARPKD to better advantage.
Although the pathogenesis of dilated tubules and macroscopic cysts is
similar, we looked at dilated tubules separately for a number of reasons.
First, the structures are exquisitely depicted using the technique we have
described. The tubules very closely correspond to the findings seen by the
pathologists on microscopy—dilated, radially oriented collecting ducts.
Second, there is the potential for this finding to be extremely specific for
ARPKD. Although macroscopic cysts have been described in children with a
variety of heritable and nonheritable renal cystic diseases, we believe that
dilated tubules may potentially be used to differentiate ARPKD from other
conditions, as described previously by Jain et al.
[8]. The pattern was seen in 20
patients in our study. One patient in our series displayed an unusual pattern
of focally dilated tubules, which were not present elsewhere in either kidney
(Fig. 5). It is not clear to us
why the finding of dilated tubules was not seen in all patients, given the
fact that all patients had tubular ectasia. We presume that the tubules were
ectatic but simply not dilated enough to be resolved by our technique.
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Fig. 5. —9-year-old girl with autosomal recessive polycystic kidney
disease. Longitudinal sonogram of left kidney shows typical pattern of tubular
dilatation. In this case, however, this finding was seen in only one portion
of one kidney. Dilated tubules were seen nowhere else in either kidney.
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Macroscopic cysts have been described previously in numerous articles
[4,
8]. We defined macroscopic
cysts as one would define any renal cyst: an anechoic structure with
imperceptible walls, with increased through-transmission. The pattern was seen
in 23 patients. In most patients, the cysts were scattered randomly throughout
the kidneys. Two patients exhibited cysts along the periphery of the kidney
(Fig. 2A,
2B) in addition to other
sonographic features of ARPKD. A case report in the literature by Currarino et
al. [9] described a peripheral
hypoechoic pattern that became more pronounced over serial examinations. At
pathologic examination, the region corresponded to an area of tubular
dilatation and the periphery was more severely involved than the remainder of
the kidney. The same process may account for the findings in two cases.
A preserved cortical rim has been described in the literature
[8,
10]. It has been postulated
that this finding is related to the fact that the peripheral cortex has little
in the way of collecting ducts, which is the structure affected in ARPKD. The
pattern was seen in 10 patients in our study.
Hyperechoic foci in the kidneys in patients with ARPKD were described by
Lucaya et al. [11]. In their
series, seven of nine patients had renal calcifications, which were visualized
on CT. The calcifications were greater in patients with more severe renal
failure. In six patients, the calcifications showed small echogenic foci
without acoustic shadowing. Lucaya et al. postulated several possible
mechanisms for the formation of calcifications in these patients, including
urine stagnation in dilated tubules and subsequent precipitation of calcium,
decreased excretion of urinary citrate, and inappropriately alkaline urine. In
our study, hyperechoic foci were seen in 16 patients. We do not have
pathologic correlation to confirm the findings of Lucaya et al., but the
appearance and ring-down artifact suggest the precipitation of some
crystalline material, perhaps calcium compounds. Avni et al.
[12] described similar
hyperechoic foci in patients with ARPKD and were able to show a correlation
between that finding and renal failure in 13 of their patients.
In conclusion, there is a spectrum of findings in the kidney in ARPKD.
These findings are very well depicted using the high-resolution technique we
have described. In our experience, high-resolution imaging adds very little
time to the standard examination. It does, however, add considerably to the
quality of the imaging examination by showing unique findings and patterns
that might not be seen using standard techniques.
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Abstract
Introduction
