Eur. Radiol.
10, 1716±1721 (2000) Ó Springer-Verlag 2000
Urogenital radiology
Review article
Acquired cystic kidney disease
P. L. Choyke
Department of Radiology, National Institutes of Health, Building 10, Room 1C660, Bethesda, MD 20892, USA
Received: 18 May 2000; Accepted: 29 June 2000
Abstract. Acquired cystic kidney disease (ACKD),
also known as acquired renal cystic disease
(ARCD,) occurs in patients who are on dialysis for
end-stage renal disease. It is generally accepted that
ACKD develops as a consequence of sustained ure-
mia and can first manifest even before dialysis is initi-
ated while the patient is still in chronic renal failure.
The role of immune suppression, particularly in
transplant recipients, in the development of ACKD,
is still under investigation. The prevalence of ACKD
is directly related to the duration of dialysis and the
risk of cancer is directly related to the presence of
cysts. Herein we review the current understanding of
the pathophysiology and imaging implications of
ACKD.
Key words: Dialysis ± Acquired cystic kidney disease
± Renal cancer ± Screening ± Renal transplantation
Introduction
Acquired cystic kidney disease is a relatively new dis-
ease, first described by Dunnill et al. in 1977 [1]. It is
not altogether surprising that ACKD was first described
so late since ACKD is an iatrogenic disease and re-
quired several prior medical breakthroughs; the first
was the widespread use of dialysis as a treatment for re-
nal failure. Dialysis only became feasible in the mid-
1960 s and by the early 1970 s had become widespread.
Coincident with this was the development of non-inva-
sive imaging techniques, such as sonography and com-
puted tomography, which allowed monitoring of the na-
tive kidneys of patients on dialysis.
Dunnill et al. first described ACKD with hemodialy-
sis; however, subsequently it has been found with every
type of dialysis including intermittent and continuous
peritoneal dialysis and within transplant recipients in
Correspondence to: P. L. Choyke
European
Radiology
chronic rejection [2, 3, 4]. The original proposal that
ACKD resulted from a specific toxin associated with di-
alysis itself has proven untenable since the disease is
universal while the methods of performing dialysis are
diverse. Numerous theories have been proposed to ex-
plain ACKD based on the idea that the chronic uremic
milieu allows the accumulation of mitogens that pro-
mote cell division or inhibit cell apoptosis [2]. It is now
recognized that the process that results in ACKD begins
well before dialysis is started. Li et al., for instance, re-
ported 16 renal cancers developing in patients with
ACKD and chronic renal failure of whom only 8 were
on dialysis [5].
Increasingly, the focus of ACKD research has been
on its natural history after renal transplantation [2]. In
chronically rejecting transplants, ACKD can develop
within the transplant itself [3]. While successful trans-
plantation decreases the number of cysts in the native
kidneys [6], pre-existing tumors may demonstrate more
aggressive behavior than was seen prior to the trans-
plant [7].
Diagnostic criteria
Cysts are common in the adult population so that the
presence of one or two cysts does not constitute
ACKD. The usual definition of ACKD requires three
or more cysts per kidney in a patient on dialysis who
does not have a hereditary cause of cystic disease such
as autosomal-dominant polycystic kidney disease or tu-
berous sclerosis [2, 8]. Using these criteria 8±13 % of pa-
tients with end-stage renal disease have ACKD before
they start dialysis [2].
Histopathology and natural history
Within the first 3 years of dialysis approximately
10±20 % develop ACKD. By 5 years, 40±60 % have
ACKD and by 10 years more than 90 % of patients ex-
P. L. Choyke: Acquired cystic kidney disease
Fig. 1. Prevalence of acquired cystic kidney disease (ACKD) as a
function of years on dialysis. Note the almost linear relationship
between dialysis duration and the frequency of ACKD
hibit ACKD (Fig. 1) [2]. Men appear to have a more se-
vere form of the disease, but women eventually develop
as severe disease [8, 9]. Ten- to 15-year follow-up studies
of kidney size reveal that the enlargement in the kidney
due to acquired cysts persisted in male patients, but the
rate of increase slowed after 13 years of hemodialysis,
whereas the enlargement in the kidney in female pati-
ents continued to increase until 17.7 years of hemodialy-
sis, revealing the slowly progressive nature of acquired
cysts in women as well as men [10]. Children are also
prone to develop ACKD. Matoo et al. [11] demonstrat-
ed that 46 % of the children on dialysis in their center
exhibited ACKD and renal cancers developed in 2 of
24 patients, a 15-year-old who had been on dialysis for
6 years and a 23-year-old who had been dialyzed for
16 years [11, 12].
The lesions within the kidney are varied in their his-
tology. The cysts are typically lined with a hyperplastic
1717
epithelium. They vary in size from microscopic to sever-
al centimeters in diameter and are usually lined by a sin-
gle or multiple layers of epithelial cells. Cystic manifes-
tations can be so marked as to mimic autosomal-domi-
nant polycystic kidney disease (Fig. 2) [13]. Papillary
proliferations are commonly seen within the cysts. Pap-
illary cystadenomas are commonly seen. Oxalate crys-
tals are common in the wall of cysts and within the inter-
stitium. Papillary adenomas occur with increased fre-
quency and renal cancers are thought to arise from ade-
nomas [14, 15, 16]. Most adenomas are small ( < 5 mm
in diameter), but approximately one-third of the tumors
are > 5 mm in diameter; thus, there appears to be a con-
tinuum of disease starting with hyperplasia of tubular
epithelium leading to tubular blockage and cyst forma-
tion, progressing to papillary cystadenomas and culmi-
nating in renal tumors of clear cell or papillary cell type
in approximately equal proportions [17]. In addition, fi-
brosis and oxalate crystal deposition are hallmarks of
ACKD.
Approximately 2±7 % of patients with ACKD ulti-
mately develop renal cancers [2, 15, 18, 19]. The mean
duration of patients on dialysis prior to the development
of cancers is 8.8 years and the mean size of clinically rec-
ognized tumors is 4 cm [8]. Ishikawa et al. [6] reported
that among 887 patients with end-stage renal disease,
512 developed ACKD while on dialysis and 19 devel-
oped renal tumors. Although in absolute terms this is a
relatively rare occurrence, compared with the general
population there is large risk (41±100 times the risk for
the general population). Moreover, the tumors are com-
monly bilateral and approximately 15 % are associated
with metastases [8].
The tumors of ACKD differ from those found in the
general population in several ways. Whereas sporadic
tumors are mostly composed of clear-cell or granular
carcinomas (90 %) and papillary cell types represent
approximately 5±7 %, in ACKD the proportion of
clear-cell carcinoma to papillary carcinoma is approxi-
Fig. 2. Acquired cystic kidney disease dem-
onstrates multiple renal cysts
1718
Fig. 3. Early ACKD on sonography. The end-stage kidney is small
and echogenic and contains several small cysts
mately 1:1 [17]. It is still unclear why the relative pro-
portion of these tumors is different in ACKD. Interest-
ingly, the patients who develop non-papillary renal can-
cers tend to do so earlier than those who develop papil-
lary renal cancers, thus suggesting a different genetic
pathway. There is no added risk of malignancy in pati-
ents with autosomal-dominant polycystic kidney dis-
ease who are not on dialysis; however, in the setting of
dialysis there is an increased risk of malignancy in this
population due to the effects of ACKD. The confusion
over whether autosomal-dominant polycystic kidney
disease is associated with an increased risk of malig-
nancy probably arises from the increased risk associat-
ed with ACKD and the occasional misdiagnosis of von
Hippel-Lindau disease as autosomal-dominant polycys-
tic disease.
Imaging
Acquired cystic kidney disease can be detected with
sonography, CT, and MRI. Sonography can be difficult
because the renal parenchyma is echogenic and the
cysts are often complex (Fig. 3). Sonography has the ad-
vantages of lower cost and no need for contrast media.
Sonography is adequate if serial studies are available
and the study is performed the same way each time [2].
As with all sonographic studies, it is operator depen-
dent.
Computed tomography is the preferred method of
imaging ACKD because it defines the extent of disease
and supplies information regarding enhancement of le-
sions (Fig. 4) [20, 21]. It is typically performed both be-
fore and after contrast media using 5-mm-thick sections,
but studies are more diagnostic when performed as a bo-
lus with early scanning as opposed to scanning after a
delay. Dialysis should be timed to occur just after con-
trast administration. A non-ionic iodinated contrast
agent should be used because it reduces the risk of fluid
shifts. Iodinated contrast is generally well tolerated by
P. L. Choyke: Acquired cystic kidney disease
patients on dialysis and provides information about the
renal volume and the presence of cystic and solid renal
masses (Figs. 5, 6).
Magnetic resonance imaging can be substituted for
CT. Although MRI images typically depict renal cysts
easily, contrast enhancement is necessary to determine
whether neovascularity is present (Fig. 6) [22].
Gadolinium chelates are dialyzable and the same
precautions should be used as with iodinated agents
[23]. Careful follow-up is important to track trends in
renal volumes and the development of solid masses.
Thus, any of the conventional cross sectional modalities
can be used to detect ACKD and ACKD-related tu-
mors.
Computed tomography and MR have the advantage
of permitting assessment of enhancement, crucial to
the detection of cancers. Of the two, CT is more widely
available and reproducible and therefore the best meth-
od [20]. Ultrasound, however, remains an excellent
technique for screening.
Hemorrhage
Approximately 50 % of patients with ACKD develop
hemorrhagic renal cysts. Bleeding into cysts results
from the underlying renal disease as well as the coagul-
opathy associated with uremia and anti-coagulants giv-
en to prevent shunt thrombosis. Bleeding usually is con-
fined within the cyst but occasionally extends into the
renal collecting system leading to hematuria or into the
perinephric space leading to flank pain (Fig. 7). Bleed-
ing can be associated with larger renal masses [24]. Peri-
nephric hematomas have been reported in up to 13 % of
patients with ACKD. Severe bleeding may require in-
tervention either as surgery or by transcatheter embo-
lization [25].
Screening
In theory, any patient on dialysis who retains their na-
tive kidneys is at risk for metastatic disease from renal
cancer. The overall risk of this is quite low: In one study
6 cancers were seen among 1470 patient years on dialy-
sis [10]. Advocates of screening suggest that a baseline
study, preferably a CT, be obtained at the onset of dialy-
sis and after 3 years on dialysis [18]. Depending on what
is seen on this baseline it is recommended that annual or
semiannual studies, again preferably CT but potentially
also with ultrasound or MRI, be obtained. Proponents
of screening suggest that early diagnosis, usually defined
as a solid mass 2 cm or more in size, will lead to better
outcomes. Given the high risk (approximately 15 %) of
developing metastatic renal cancer this approach seems
compassionate and reasonable [8].
However, all screening comes at a cost which must at
least balance the benefits. In the case of screening for
cancers in ACKD it is argued that the risk of dying
from other co-morbid conditions, such as severe diabe-
tes or hypertension, usually outweighs the potential
P. L. Choyke: Acquired cystic kidney disease 1719

4a 4b

5 6

Fig. 4 a, b. Computed tomography in the evaluation of ACKD. ACKD. This policy enriches the pool of patients who
a Precontrast scan demonstrates small cystic kidneys with ascites will likely benefit from screening. But it also means
from residual peritoneal dialysate. b After iodinated contrast me-
that a few older patients with ACKD may die of meta-
dia, a distinct solid, papillary renal cancer was demonstrated.
(Courtesy of D. Hartman) static renal cancer.
An important point that is often overlooked in the
Fig. 5. Renal cancer in a patient with autosomal-dominant poly-
cystic kidney disease and ACKD. This patient had been on dialysis
debate over screening is the worldwide variation in sur-
for 7 years for advanced polycystic disease. The tumor which arises vival rates of patients on dialysis. In developing nations,
from the medial aspect of the left kidney likely developed as a con-
sequence of dialysis and is unrelated to the underlying hereditary
polycystic kidney
Fig. 6. Magnetic resonance imaging in the evaluation of ACKD.
T1-weighted MRI in patient on dialysis demonstrates multiple
cysts from early ACKD

benefits for most patients [2]. Sarasin et al. studied the

potential benefits of screening using a decision analysis
model and found that screening provided significant
benefits only to those patients with a life expectancy
of 25 years or more [26]. In such patients their model
predicted a 1- to 6-year gain in life expectancy for pati-
ents in whom tumors are discovered. However, the gain
for older patients on dialysis, whose prognosis is limited
by their underlying disease, could be measured only in
days. This has led to policy, at least in the United Fig. 7. Hemorrhagic ACKD. An acute hemorrhage is seen in the
States, that screening be reserved for patients who left kidney and perinephric space occurring 2 days after dialysis.
have a good medical condition, who have been on dial- Mild changes in ACKD are present in the right kidney. The patient
ysis for more than 5 years, and who have signs of required an emergency nephrectomy
1720
Fig. 8. Transplant candidate with advanced ACKD. This patient
had been on dialysis for 13 years but is now a renal transplant can-
didate. Pretransplantation screening CT demonstrates enlarged
kidney with multiple cysts. The right renal pelvis is filled with
opacified urine from the slowly excreting kidney. Patients who
have been on dialysis for long periods should have a pretransplant
examination
dialysis is a rarity and the issue of screening is not realis-
tic. In developed, countries such as the United States,
the mortality of patients on dialysis is among the highest
in the world and is often attributed to the uneven quality
of care particularly among the poor [27]. More affluent
patients avoid dialysis completely or do better once on
dialysis. In Japan, for instance, the median survival of
patients on dialysis is much better than in the United
States. This makes the recommendation for screening
for most ACKD patients more reasonable in that coun-
try.
Patients with ESRD are at risk for malignancies oth-
er than renal cancer. Port et al. reviewed 4161 ESRD
patients and found a relative risk of 3.8 for in situ malig-
nancies overall, 5.0 for renal cancers, 4.3 for uterine can-
cers, and 1.8 for prostate cancer. Other associated malig-
nancies include non-Hodgkin's lymphoma, sarcomas,
and skin cancers [28].
Transplantation
Many patients undergo dialysis for many years before
receiving a renal allograft. In general, the native kidneys
are left in place after transplantation since removal is
generally considered unnecessary and it is felt that the
native kidneys may contribute small amounts of ery-
thropoetin and small volumes of urine that improve the
quality of life (Fig. 8).
After successful transplantation, the cystic disease
associated with ACKD regresses and the kidneys return
to their baseline atrophic size [6]; however, tumors asso-
ciated with ACKD may become more aggressive after
transplantation. This is likely due to the loss of host im-
munity associated with suppression of allograft rejec-
tion. Kliem et al. reported that among 2372 renal trans-
plants 12 (0.5 %) developed renal cancers in the native
P. L. Choyke: Acquired cystic kidney disease
kidneys at a mean of 6 years after transplantation (range
0.5±15 years) [29]. Most of the these patients had had
ACKD and 4 of the 12 died of metastatic disease.
Heinz-Peer et al. reported that among 385 transplant re-
cipients 6 (1.6 %) developed renal cancers the majority
of which metastasized [22, 30, 31]. Doublet et al. report-
ed a 3.9 % rate of renal cancers developing in the native
kidneys of transplant recipients [32]; thus, there appears
to be a small risk of developing renal cancer in native
kidneys after transplantation but a risk that is substan-
tially greater than the baseline risk in the general popu-
lation; moreover, the tumors appear to be more aggres-
sive. This has prompted recommendations for pre-trans-
plant baseline evaluations of the native kidneys with
consideration to remove native kidneys severely affect-
ed by ACKD.
Transplant allografts themselves become susceptible
to ACKD if there is a prolonged period of rejection
and renal failure [3]. Even after transplantation periodic
surveillance of the kidneys, both native and transplant,
is warranted, although firm guidelines backed by hard
data are not yet available [33, 34].
Conclusion
Acquired cystic kidney disease is a consequence of pro-
longed uremia during dialysis and develops in direct re-
lation to the duration of dialysis. Renal tumors, both
clear cell and papillary, form at an increased rate but
are a relatively unusual cause of death compared with
underlying diseases that caused renal failure (diabetes,
hypertension, systemic diseases). Acquired cystic kid-
ney disease and tumors can develop in children who
are on dialysis.
Screening is controversial since it is so expensive and
the yield is relatively low. Almost all authors agree that
dialysis patients who are in generally good medical con-
dition and who have a substantial expected survival of
approximately 20 years warrant screening. Computed
tomography is usually considered to be the best method
of screening, although sonography and MRI are reason-
able choices. Sonography has the advantages of lower
cost and non-invasiveness but is limited by a lower sen-
sitivity and specificity. Since it is difficult to accurately
gauge survival in any one patient, the guidelines are in-
terpreted in a variety of ways by different physicians.
Our own policy is to scan patients periodically while on
dialysis with ultrasound, obtaining CTs if the sonogra-
phy suggests a solid mass. Computed tomography or
MRI is performed prior to transplantation in patients
who have been on dialysis for substantial periods of
time.
Although the cysts of ACKD regress after successful
renal transplantation, pre-existing tumors become
more aggressive after transplantation and can metasta-
size. This is likely due to the altered host immunity.
Screening at baseline and periodically thereafter ap-
pears warranted until more definitive studies of efficacy
have been performed.
P. L. Choyke: Acquired cystic kidney disease
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