Extrarenal manifestations of autosomal dominant polycystic kidney disease - UpToDate 12/08/17 23)59

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Extrarenal manifestations of autosomal dominant polycystic kidney disease

Authors: William M Bennett, MD, Vicente E Torres, MD

Section Editor: Ronald D Perrone, MD
Deputy Editor: Alice M Sheridan, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2017. | This topic last updated: Sep 26, 2016.

INTRODUCTION — Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cysts in the
kidneys and, in many cases, is associated with cysts in the liver and pancreas that can be helpful in confirming
the diagnosis. In addition, patients may have a variety of other abnormalities, many of which are consistent with
a generalized defect in epithelial cell differentiation and/or extracellular matrix function as a primary expression of
the genetic abnormality in this disorder [1-5]. (See "Genetics of autosomal dominant polycystic kidney disease
and mechanisms of cyst growth".)

This topic reviews the major extrarenal manifestations of ADPKD. The diagnosis, screening, and treatment of
ADPKD are discussed elsewhere. (See "Diagnosis of and screening for autosomal dominant polycystic kidney
disease" and "Course and treatment of autosomal dominant polycystic kidney disease".)

MAJOR EXTRARENAL COMPLICATIONS — The major extrarenal complications of ADPKD are:

● Cerebral aneurysms
● Hepatic and pancreatic cysts
● Cardiac valve disease
● Colonic diverticula
● Abdominal wall and inguinal hernia
● Seminal vesicle cysts

Cervicocephalic artery dissections, dolichoectasias [6,7], and central retinal vascular occlusions [8] have also
been associated with ADPKD.

The mechanism of cyst formation is discussed elsewhere (see "Genetics of autosomal dominant polycystic
kidney disease and mechanisms of cyst growth", section on 'Mechanism of cyst formation and growth').
Malformations of selected vasculature, including intracranial aneurysms and aortic root dilatation (normal
diameter ≤35 mm), may be due to altered expression and/or function of the PKD gene in arterial smooth muscle
cells [9].

CEREBRAL ANEURYSM — A ruptured cerebral aneurysm, resulting in a subarachnoid or intracerebral

hemorrhage, is the most serious complication of PKD [2]. The prevalence of aneurysms in ADPKD is
approximately 5 percent in young adults and increases with age to as high as 20 percent in patients 60 years

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and older [2,3,10-13].

Patients with a family history of intracranial aneurysm or subarachnoid hemorrhage appear to be at greatest risk
[2,6,13-15]. Data from two studies, for example, demonstrated asymptomatic intracranial aneurysms in 17 of 78
patients (22 percent) with and 35 of 348 patients (10 percent) without a positive family history [10,13]. The
position of the mutation also may be weakly associated with the risk of intracranial aneurysm [16].

Aneurysm rupture in ADPKD most often occurs with larger aneurysms, usually before the age of 50 years and/or
in patients with poorly controlled hypertension [12]. However, both hypertensive stroke and intracerebral
hemorrhage are more common than aneurysm rupture in ADPKD.

In a review of 77 patients with intracranial aneurysm (71 with previous aneurysm rupture), the following additional
characteristics were noted [14]:

● One-half of patients had normal renal function.

● The middle cerebral artery was usually involved, but 31 percent had multiple aneurysms.

● Death or severe disability occurred in 48 percent in the 71 patients with a ruptured aneurysm.

The most common complaint with a subarachnoid hemorrhage is the acute onset of severe headache, frequently
associated with nausea and vomiting (see "Clinical diagnosis of stroke subtypes", section on 'Subarachnoid
hemorrhage'). As an example, a prospective study of 148 patients (not with ADPKD) presenting with sudden and
severe headache found subarachnoid hemorrhage in 25 percent [17].

Immediate evaluation is essential in this setting to preserve neurologic function. The evaluation of patients with
suspected subarachnoid hemorrhage is discussed elsewhere. (See "Clinical manifestations and diagnosis of
aneurysmal subarachnoid hemorrhage", section on 'Diagnosis of subarachnoid hemorrhage'.)

In view of the poor prognosis associated with a major subarachnoid hemorrhage, early diagnosis of symptoms
related to growth or change of an intracranial aneurysm is important. As an example, some patients with
subarachnoid hemorrhage have warning symptoms of severe headache from a small bleed (also called a
warning leak or sentinel bleed), usually occurring within the previous 30 days. However, most first hemorrhages
appear to be serious [17]. (See "Clinical manifestations and diagnosis of aneurysmal subarachnoid hemorrhage",
section on 'Clinical presentation'.)

Natural history — An important issue is the natural history of intracerebral aneurysms in patients with ADPKD
[18,19].

One of the better studies evaluated the risk of recurrent aneurysm formation and/or an increase in size of an
existing aneurysm among ADPKD patients with a history of either a ruptured or intact intracranial aneurysm [19].
In this report, 20 ADPKD patients, 11 and 9 of whom had ruptured and intact intracranial aneurysms,
respectively, were followed for a mean of approximately 15 years from the time of initial diagnosis [19]. All of the
patients with ruptured aneurysms and one with an intact aneurysm had undergone surgery at diagnosis.

One patient had recurrent subarachnoid hemorrhage, and no patient died during the study. On follow-up imaging
with magnetic resonance angiography (MRA) or conventional angiography at a mean period of 11.4 years, five

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patients (25 percent) had a new aneurysm in a different location, and two of the same five also had an increase
in size of the previously known aneurysm. Ten patients underwent neurosurgery; the discrepancy between the
number requiring surgery and the number with intracerebral aneurysm changes was due to the re-evaluation and
different interpretation of the initial radiographic studies, resulting in surgery in patients initially not thought to be
at risk for rupture.

When the groups with and without aneurysm changes were compared, no clinical factors were significantly
associated with the development of a new aneurysm or an increase in size of an existing aneurysm. Factors that
were studied included age at diagnosis, time to restudy, proportion of patients with initially ruptured aneurysm,
time of follow-up, time to surgery, and proportion of patients requiring surgery.

The best available data from the general population suggest that the risk of subarachnoid hemorrhage from
rupture of small aneurysms (≤7 mm) is low in patients without a prior subarachnoid hemorrhage. (See
"Unruptured intracranial aneurysms", section on 'Risk of aneurysm rupture'.)

This observation appears to apply to patients with ADPKD. This was illustrated in a study of 18 patients with
ADPKD who had small (<7 mm), asymptomatic intracranial aneurysms on initial screening [20]. At a mean follow-
up of eight to nine years, there were no aneurysm ruptures. A larger study from the same institution included 45
saccular aneurysms detected in 38 patients from 36 families. Most were small (median diameter 3.5 mm) and in
the anterior circulation (84 percent). Median age at diagnosis was 49 years. During cumulative clinical follow-up
of 316 years, no aneurysm ruptured [21].

Screening

Indications for screening — We generally offer, although do not necessarily recommend, screening to adult
ADPKD patients and discuss with them potential risks of screening versus the risks of rupture of an undetected
aneurysm.

We recommend routine screening for high-risk patients, such as those with a previous rupture, a positive family
history of an intracerebral bleed or intracranial aneurysm, warning symptoms, a high-risk occupation in which
loss of consciousness would place the patient or others at extreme risk, and prior to surgery that is likely to be
associated with hemodynamic instability with hypertension [2,4,14].

Some, but not all, centers screen all ADPKD patients who are undergoing renal transplantation. Other centers
screen ADPKD patients awaiting renal transplantation who have a history of headaches or family history of
aneurysm. (See "Evaluation of the potential renal transplant recipient", section on 'Cerebrovascular disease'.)

We also screen patients who require chronic anticoagulation for disorders such as deep vein thrombosis or atrial
fibrillation. Although data are limited, studies in patients with unruptured intracranial aneurysms (most often not
related to ADPKD) have concluded that, although it is not known whether anticoagulation increases the risk of
intracranial bleeding, if rupture occurs, anticoagulation increases the severity of bleeding [2,4,14]. (See
"Anticoagulant and antiplatelet therapy in patients with an unruptured intracranial aneurysm".)

We recommend not screening children (ie, <18 years) with ADPKD, because aneurysmal rupture in childhood is
extremely rare.

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There are no randomized, controlled studies to inform decisions regarding screening [22]. (See "Screening for
intracranial aneurysm", section on 'Relatives of patients with cerebral aneurysm'.)

Among patients with initially negative radiographic studies, we rescreen every five years those who have a family
history of aneurysm, intracerebral bleeding, or cerebrovascular accident (CVA). Among patients who have
initially negative studies and no family history of CVA or hemorrhage, the role of additional screening is unclear,
with some clinicians continuing to screen every five years. There are only limited published data upon which to
base recommendations for rescreening such patients. In a prospective report, among 76 ADPKD patients who
had an initially negative radiographic imaging procedure, at follow-up imaging at a mean period of 9.8 years, two
patients (2.6 percent) were found to have a new intracranial aneurysm, but only one occurrence was clinically
significant [23].

Monitoring of patients who have aneurysms that do not require immediate surgical intervention is discussed
below. (See 'Monitoring patients with small aneurysms' below.)

Methods of screening — The preferred methods of screening for aneurysm include time-of-flight MRA
without gadolinium and high-resolution computed tomography angiography (CTA) [11,13,20,24,25]. We generally
prefer to use MRA for screening and use CTA only if there are contraindications to MRA (such as prior surgical
clipping of aneurysm).

Both imaging modalities have been shown to have a high sensitivity for detection of aneurysms 3 to 5 mm or
larger (see "Screening for intracranial aneurysm", section on 'Choice of screening test'). Cerebral angiography is
invasive and may be associated with an increased risk of cerebral bleeding or stroke [11]. Time-of-flight MRA
does not require gadolinium contrast and can be performed safely at any level of glomerular filtration rate (GFR).
Administration of gadolinium should be avoided in patients with moderate to severe renal disease because of the
risk of nephrogenic systemic fibrosis (NSF).

Indications for intervention — The indications for surgical intervention for unruptured cerebral aneurysm are
the same for patients with ADPKD as for the non-ADPKD population and are discussed elsewhere. (See
"Unruptured intracranial aneurysms", section on 'Whom to treat'.)

Patients with known, unruptured aneurysms who are managed conservatively should be instructed to avoid
uncontrolled hypertension, smoking, heavy alcohol consumption, stimulant medications, illicit drugs, and
excessive straining and Valsalva maneuvers.

Monitoring patients with small aneurysms — Among patients who have aneurysms that do not require
immediate surgical intervention, we suggest follow-up monitoring with MRA or CTA annually for two to three
years and every two to five years thereafter if the aneurysm is clinically and radiographically stable. However, it is
not unreasonable to reimage newly detected, small aneurysms at six months, since there is evidence that newly
formed, small aneurysms may be at higher risk of rupture than older, more stable aneurysms (see "Unruptured
intracranial aneurysms"). Longer reimaging intervals are certainly appropriate if the six-month study shows no
significant change.

There are limited data concerning the role of follow-up radiographic monitoring in patients found to have small
aneurysms at screening.

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● In one study, 30 MRAs were performed in 10 patients who had asymptomatic aneurysms measuring 1.5 to
6.5 mm over a mean interval of 30 months [26]. No change in aneurysm size or the development of new
aneurysms was reported. Serial studies in three patients with symptomatic aneurysms also failed to detect
de novo aneurysm formation over an eight-year period.

● In one study of 20 patients with a history of ruptured (11 patients) or asymptomatic (9 patients) intracranial
aneurysms, the proportion of patients with progressive disease in the intracranial circulation at time of
restudy (mean 11.4 years [range of 1.6 to 30.2 years] from the time of initial diagnosis) was smaller among
patients with asymptomatic aneurysms compared with those with a history of ruptured aneurysms (11
versus 36 percent, respectively) [19]. However, the number of patients was small, and this difference was
not statistically significant.

● One study included 38 asymptomatic patients with 45 aneurysms who were followed with MRA [21]. Over a
cumulative follow-up of 243 years, one de novo aneurysm was detected and increased in size from 2 to 4.4
mm over 144 months, and two previously detected aneurysms grew from 4.5 to 5.9 mm and 4.7 to 6.2 mm
after 69 and 184 months, respectively [21].

Safety of anticoagulation — Patients with ADPKD may require chronic anticoagulation with warfarin for
disorders such as deep vein thrombosis or atrial fibrillation. As noted above, such patients should be screened
for the presence of an aneurysm. (See 'Screening' above.)

Patients with an aneurysm should be told about the relative risks and benefits of anticoagulation and be
evaluated for possible nonpharmacologic therapies (eg, inferior vena cava filter for deep vein thrombosis and
radiofrequency ablation for atrial fibrillation). Although data are limited, studies in patients with unruptured
intracranial aneurysms (most often not related to ADPKD) have concluded that it is not known if warfarin
increases the risk of intracranial bleeding, but, if rupture occurs, anticoagulation increases the severity of
bleeding. (See "Anticoagulant and antiplatelet therapy in patients with an unruptured intracranial aneurysm".)

Those without an aneurysm probably have a risk of cerebral hemorrhage from anticoagulation that is similar to
hypertensive patients who do not have ADPKD. (See "Risk of intracerebral bleeding in patients treated with
anticoagulants", section on 'Blood pressure control'.)

HEPATIC CYSTS — As with renal cysts, the prevalence of hepatic cysts increases with age. Earlier studies that
utilized ultrasound for screening reported a prevalence of approximately 10 to 20 percent below the age of 30
years and 50 to 70 percent over the age of 60 years [27-29]. However, in a study of 230 patients with ADPKD
between the ages of 15 and 46 years, magnetic resonance imaging (MRI), which is much more sensitive than
ultrasound for the detection of small cysts, identified hepatic cysts in 83 percent [30]. The extent of the cystic
disease in the kidney and the liver is only weakly correlated, suggesting that, in addition to the PKD mutations,
other factors distinct for each organ are important for the development and progression of PKD and polycystic
liver disease (PLD) [31]. In contrast to the renal phenotype, the ADPKD genotype was not associated with the
severity or growth rate of PLD in ADPKD patients. This finding indicates that modifiers beyond the disease gene
significantly influence the liver phenotype [32].

Hepatic cysts occurring in ADPKD are different from autosomal dominant PLD (ADPLD). Patients with ADPLD
may have no or only few renal cysts, but mice with knockout of either of the two known ADPLD genes have

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polycystic kidneys [33]. (See "Diagnosis and management of cystic lesions of the liver", section on 'Polycystic
liver disease'.)

Although the overall prevalence of a polycystic liver in patients with ADPKD is similar in men and women, women
may develop cysts at an earlier age, and massive cysts occur almost exclusively in women, particularly those
who have had several pregnancies [27,28,30]. Such acceleration of hepatic cyst growth may be due to an
underlying sensitivity of the cysts to female steroid hormones. Consistent with this hypothesis is the observation
that postmenopausal estrogen may be associated with selective enlargement of hepatic cysts, as well as the
hepatic parenchyma [34]. Further supporting the role of female hormones in the progression of PLD is that 58
percent of females >48 years of age with severe PLD (height-adjusted liver volume >1800 mL/m) had a
significant regression in liver volume on follow-up imaging, whereas the liver continued to enlarge in males [32].

Most patients remain asymptomatic with preserved hepatic function. However, patients rarely develop pain
(which may require decompression of the cyst if it is persistent and severe) and/or cyst infection (which requires
therapy with an antimicrobial, such as a fluoroquinolone, that can penetrate the cyst and, in some cases,
percutaneous drainage) [2,29,35]. Acute pain usually results from cyst infection or hemorrhage and rarely from
rupture or torsion [29]. Radionuclide imaging and, more recently, 18F-fluorodeoxyglucose positron emission
tomography scanning have been used for diagnosis of hepatic cyst infection [36,37].

Partial hepatic resection has been attempted with some success in patients with massive symptomatic cysts
[29,38,39]; however, this procedure should be limited to refractory patients and performed only in centers with
experience in hepatic surgery. Liver transplantation and combined liver/kidney transplantation have been
performed in patients with severe, symptomatic disease [40]. Rarely, invasive management is undertaken for the
management of refractory pain. In patients who are not surgical candidates, percutaneous transcatheter hepatic
artery embolization may be a treatment option [41].

The immunosuppressive agent, sirolimus, appears to decrease polycystic liver volume, possibly via an
antiproliferative effect [42]. In a retrospective study, liver volume was assessed in seven kidney transplant
patients administered sirolimus-mycophenolate-prednisone and nine recipients given tacrolimus-mycophenolate-
prednisone [42]. At 19 months, the sirolimus-based regimen resulted in a decrease in mean liver volume of 12
percent, while the mean liver volume increased by 14 percent in those individuals using a tacrolimus-based
regimen. Further data are required to understand the role, if any, of sirolimus in this setting. A randomized,
controlled trial has shown that adding everolimus to octreotide in PLD does not increase the liver volume-
reducing effect of octreotide [43].

Somatostatin may reduce renal and liver cyst fluid accumulation among patients with PKD or isolated PLD [44-
47]. (See "Course and treatment of autosomal dominant polycystic kidney disease", section on 'Somatostatin'.)
The role of somatostatin analogs such as octreotide and lanreotide in the treatment of severe PLD needs to be
better defined.

PANCREATIC CYSTS — Pancreatic cysts occur in approximately 7 to 10 percent of patients with ADPKD [48-
50]. They have also been demonstrated in a mouse model of ADPKD due to both PKD1 and PKD2 gene
mutations, which are responsible for almost all cases of ADPKD [51,52]. Associations with intraductal papillary
mucinous neoplasm has also been reported [53]. (See "Classification of pancreatic cysts" and "Genetics of

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autosomal dominant polycystic kidney disease and mechanisms of cyst growth", section on 'Genetics'.)

CARDIAC DISEASE — Valvular abnormalities of unclear clinical significance can be detected by cardiac
ultrasonography in 25 to 30 percent of patients with ADPKD [2,54-57]. The most common abnormalities include
mild mitral valve prolapse and aortic regurgitation; less frequent lesions include mitral and/or tricuspid
regurgitation [2,54-57]. Generalized abnormalities in collagen and/or extracellular matrix may be responsible for
the valve disease in ADPKD; aortic regurgitation, for example, may result from dilatation of the aortic root and
annulus [54]. (See "Definition and diagnosis of mitral valve prolapse" and "Clinical manifestations and diagnosis
of chronic aortic regurgitation in adults".)

Most patients are asymptomatic, and the incidence of audible murmurs is substantially lower than abnormalities
on ultrasonography [2,55]. Nevertheless, the lesions may progress over time and become severe enough to
require valve replacement [54]. The use of antimicrobial prophylaxis among patients with valvular lesions is
discussed elsewhere. (See "Antimicrobial prophylaxis for bacterial endocarditis".)

Preliminary evidence suggests that PKD may also be associated with an increased incidence of coronary
aneurysms and coronary artery dissection [58,59]. In one study, for example, the prevalence of coronary
aneurysms (defined as an increased diameter of ≥50 percent or pathologic ectasia) was evaluated in 30 patients
with ADPKD and in the same number of controls with similar degrees of renal dysfunction and equivalent
demographic characteristics but without ADPKD [60]. Both groups underwent coronary angiography for
conventional clinical indications. Aneurysms were present in four ADPKD and two control patients, while ectatic
lesions were detected in five ADPKD, but no control individuals. Coronary artery dissection has been described
in isolated case reports.

Asymptomatic pericardial effusions appear to occur at increased frequency in patients with ADPKD. This was
best shown in a retrospective analysis from the Mayo Clinic, in which the presence and severity of pericardial
effusions were analyzed by computed tomography (CT) among 60 patients with ADPKD (mean serum creatinine
concentration 1.8 mg/dL [160 micromol/L]), 100 patients with chronic kidney disease (CKD) not due to ADPKD
(mean serum creatinine concentration 1.8 mg/dL [160 micromol/L]), and 100 healthy kidney donors [61]. A
pericardial effusion was found in 35, 9, and 4 percent of ADPKD patients, patients with CKD, and healthy donors,
respectively. A moderate to high effusion severity score was noted in nearly 50 percent of patients with ADPKD
and an effusion but in none of the others. Despite the size of these effusions, they were generally well tolerated
and clinically inconsequential.

We do not routinely screen all patients with ADPKD with echocardiography. We suggest that patients who have
heart murmurs or signs or symptoms of cardiac dysfunction be assessed by echocardiography, with further
evaluation as indicated. (See "Determining the etiology and severity of heart failure or cardiomyopathy", section
on 'Echocardiography' and "Clinical manifestations and diagnosis of asymptomatic left ventricular systolic
dysfunction", section on 'Diagnosis and evaluation'.)

DIVERTICULA AND HERNIAS — Colonic diverticula and abdominal wall and inguinal hernias are seen with
increased frequency in patients with ADPKD [2,62-66]. As examples:

● Colonic diverticula are found in many ADPKD patients on maintenance dialysis [62], but may not occur with
increased frequency in those without end-stage renal disease (ESRD) [64]. Symptoms that may occur

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include abdominal pain (which may be difficult to distinguish from the pain induced by the renal cysts),
diarrhea, and heme-positive stools. The incidence of complications, such as colonic perforation, appears to
be higher than seen with diverticular disease in patients without PKD and may be increased following
transplant [2,62]. (See "Clinical manifestations and diagnosis of acute diverticulitis in adults".)

● Diverticular disease of the duodenum, presenting with nausea, vomiting, abdominal pain, malabsorption, bile
or pancreatic duct obstruction, may also be associated with ADPKD [67].

Abdominal wall hernias were, in one series, found in 45 percent of patients with ADPKD; the incidence was
much higher than in patients with other causes of chronic renal failure or general surgery patients (8 and 4
percent, respectively) [65]. Patients with ADPKD treated with continuous ambulatory peritoneal dialysis are
also at increased risk for an indirect inguinal hernia, probably due to a high frequency of a patent processus
vaginalis [66]. (See "Abdominal hernias in continuous peritoneal dialysis".)

OTHER — An association between abdominal aortic aneurysms and ADPKD has been proposed. However, a
study that compared 139 patients with ADPKD and 149 controls was unable to demonstrate by ultrasonography
an increase in either aortic diameter or the incidence of aneurysm formation in the patients with ADPKD [68].
Although aortic aneurysms do not appear to be an intrinsic feature of ADPKD, there may be some increase in
risk in patients with uncontrolled hypertension.

Seminal vesicles cysts are present in 40 percent of male ADPKD patients [69-71]. Seminal vesicle cysts rarely
result in infertility [72]. Defective sperm motility is another cause of male infertility in ADPKD [73,74]. Arachnoid
membrane cysts occur in 8 percent and are usually an asymptomatic, incidental finding [75,76]. They may
increase the risk for subdural hematomas [77,78]. Spinal meningeal diverticula may occur with increased
frequency and rarely present with intracranial hypotension due to cerebrospinal fluid leak [79]. A review of
computed tomography (CT) scans revealed a threefold-increased prevalence of bronchiectasis in ADPKD
patients compared with a control population (37 versus 13 percent) [80].

There does not appear to be an enhanced risk of ovarian cysts among women with ADPKD [81,82].

MALIGNANCY — The overall risk of cancer may be increased among patients with ADPKD. This was suggested
by a nationwide cohort study from Taiwan that compared cancer incidence among 8692 individuals with and
without ADPKD [83]. After adjusting for multiple variables (age, sex, frequency of medical visits, comorbidities),
compared with controls, ADPKD patients had a higher overall risk of cancer (hazard ratio 1.83, 95% CI 1.57-
2.15). In contrast, another registry study of posttransplant ADPKD patients, when appropriately adjusted, showed
a lower overall incidence of cancer [84].

The risk of renal cell cancer is discussed elsewhere. (See "Hereditary kidney cancer syndromes", section on
'Polycystic kidney disease'.)

The risk of renal cell cancer does not appear to be higher among patients with ADPKD. This issue is discussed
elsewhere. (See "Hereditary kidney cancer syndromes", section on 'Polycystic kidney disease'.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and
"Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given condition. These

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articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond
the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written
at the 10th to 12th grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these
topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on
"patient info" and the keyword(s) of interest.)

● Basics topic (see "Patient education: Polycystic kidney disease (The Basics)")

● Beyond the Basics topic (see "Patient education: Polycystic kidney disease (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

● The major extrarenal complications of autosomal dominant polycystic kidney disease (ADPKD) include
cerebral aneurysms, hepatic and pancreatic cysts, cardiac valve disease, colonic diverticula, abdominal wall
and inguinal hernias, and seminal vesical cysts. (See 'Introduction' above.)

● A ruptured cerebral aneurysm, resulting in a subarachnoid or intracerebral hemorrhage, is the most serious
complication of PKD. Aneurysms occur in approximately 5 to 20 percent of patients with ADPKD. Patients
with a family history of intracranial aneurysm or subarachnoid hemorrhage appear to be at greatest risk.
Aneurysm rupture in ADPKD most often occurs with larger aneurysms, usually before the age of 50 years
and/or in patients with poorly controlled hypertension. (See 'Cerebral aneurysm' above.)

● We offer, although do not necessarily recommend, screening for cerebral aneurysm to adult ADPKD patients
and discuss with them potential risks of screening versus the risks of rupture of an undetected aneurysm.
We screen all ADPKD patients who are undergoing renal transplantation. We also screen patients who
require chronic anticoagulation for disorders such as deep vein thrombosis or atrial fibrillation. We
recommend not screening children (ie, <18 years) with ADPKD, because aneurysmal rupture in childhood is
extremely rare.

Among patients with initially negative radiographic studies, we rescreen every five years those who have a
family history of intracerebral bleeding or cerebrovascular accident (CVA). (See 'Indications for screening'
above.)

● Screening modalities for cerebral aneurysm include high-resolution computed tomography angiography
(CTA) or time-of-flight magnetic resonance angiography (MRA). Time-of-flight MRA does not require
gadolinium contrast and can be performed safely at any level of glomerular filtration rate (GFR). (See
'Screening' above.)

● Among patients who have aneurysms that do not require surgical intervention, we suggest follow-up
monitoring with CTA or MRA annually for two to three years and every two to five years thereafter if the
aneurysm is clinically and radiographically stable. However, it is not unreasonable to reimage newly
detected, small aneurysms at six months, since there is evidence that newly formed, small aneurysms may
be at higher risk of rupture than older, more stable aneurysms. (See 'Monitoring patients with small

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aneurysms' above.)

● Although most patients remain asymptomatic with preserved hepatic function, some develop pain (which
may require decompression of cysts if it is persistent and severe) and/or cyst infection. Pancreatic cysts may
also occur, though less commonly than hepatic cysts. Cardiac manifestations of ADPKD include valvular
abnormalities, coronary aneurysms, and asymptomatic pericardial effusions. (See 'Cardiac disease' above
and 'Hepatic cysts' above.)

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1990; 16:403.
2. Fick GM, Gabow PA. Hereditary and acquired cystic disease of the kidney. Kidney Int 1994; 46:951.
3. Watson ML. Complications of polycystic kidney disease. Kidney Int 1997; 51:353.
4. Grantham JJ. Clinical practice. Autosomal dominant polycystic kidney disease. N Engl J Med 2008;
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Topic 1679 Version 16.0

Contributor Disclosures
William M Bennett, MD Nothing to disclose Vicente E Torres, MD Grant/Research/Clinical Trial Support
[Otsuka (ADPKD)]. Ronald D Perrone, MD Grant/Research/Clinical Trial Support: Otsuka [Polycystic kidney
disease (Tolvaptan)]. Consultant/Advisory Boards: Otsuka [Polycystic kidney disease (Tolvaptan)]; Novartis
[Polycystic kidney disease]; Misubishi Tanabe [Polycystic kidney disease]; Sanofi-Genzyme [Polycystic kidney
disease]. Alice M Sheridan, MD Nothing to disclose

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