Diagnosis of and Screening for Autosomal Dominant Polycystic Kidney Disease

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Diagnosis of and screening for autosomal dominant polycystic kidney disease

Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Jun 2013. | This topic last updated: Jan 11, 2013.

INTRODUCTION Autosomal dominant polycystic kidney disease (ADPKD) is a common disorder,

occurring in approximately 1 in every 400 to 1000 live births [1-3]. It is estimated that less than one-half of

these cases will be diagnosed during the patient's lifetime, as the disease is often clinically silent [1].

Approximately 85 percent of families with ADPKD have an abnormality on chromosome 16 (PKD1 locus)

that is tightly linked to the alpha-globin gene locus [4]. The remaining patients have a different defect that

involves a gene on chromosome 4 (the PKD2 locus). (See "Genetics of autosomal dominant polycystic

kidney disease and mechanisms of cyst growth".)

Patients with PKD2 have a less severe phenotype than those with PKD1, but neither disorder is benign

[5]. Cysts occur later in PKD2 disease, as does end-stage renal disease (mean age 74.0 versus 54.3

years in PKD1) [6]. As a result, false negative results are more likely when screening young subjects with

PKD2 disease. (See "Course and treatment of autosomal dominant polycystic kidney disease".)

The diagnosis of and screening for ADPKD will be reviewed here. The course and treatment of thisdisorder are discussed separately. (See "Course and treatment of autosomal dominant polycystic kidney

disease".)

OVERVIEW The diagnosis of ADPKD relies principally upon imaging of the kidney [7]. Typical findings

include large kidneys and extensive cysts scattered throughout both kidneys. Because of cost and safety,

ultrasonography is most commonly used as the imaging modality. In certain settings, genetic testing is

required for a definitive diagnosis.

Important issues related to the diagnosis of ADPKD include the presence or absence of a family history of

the disease, the number and types of renal cysts, and the age of the patient.

POSITIVE FAMILY HISTORY

Screening and diagnosis of asymptomatic individuals Screening for the diagnosis of ADPKD in an

asymptomatic individual at risk because of a positive family history usually relies upon imaging of the

kidney. Among at risk individuals, ultrasonography of the kidneys is usually the initial modality used for

screening and diagnosis. Since this technique is less reliable in younger individuals, genetic diagnosis

using linkage or DNA analysis and/or an alternative imaging modality can be performed when a definitive

diagnosis is required. (See 'Genetic testing' below and 'Other imaging modalities' below.)

In children (less than 18 years of age), we recommend NOT screening. This is principally because the

Official reprint from UpToDate

www.uptodate.com 2013 UpToDate

AuthorsVicente E Torres, MDWilliam M Bennett, MD

Section EditorRonald D Perrone, MD

Deputy EditorAlice M Sheridan, MD

Page 1 of 15Diagnosis of and screening for autosomal dominant polycystic kidney disease

8/4/2013http://www.uptodate.com/contents/diagnosis-of-and-screening-for-autosomal-dominant-pol ...


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adverse consequences associated with a positive diagnosis prior to symptoms in young individuals (such

as career, educational, emotional, and insurability issues) far outweigh any benefits since effective

therapies are not yet available. Nevertheless, children at risk for ADPKD should be monitored for early

disease presentations that require treatment. Among these, hypertension is underrecognized.

In adults (greater than 18 years of age), we recommend screening in potential living related kidney

donors given the adverse medical consequences of transplanting a kidney from a donor with ADPKD. It is

important to realize, however, that all potential kidney donors undergo imaging of the kidneys. In other at-risk adults, the decision to screen for the disease should be based upon patient's preferences and values

after the benefits and adverse consequences of certainty concerning the diagnosis are fully understood.

Prior to testing, counseling by experienced staff must be performed. The benefits derived from testing

include knowledge concerning the diagnosis, appropriate family planning, the ability to detect and treat

complications associated with the disease, reassurance of unaffected individuals, and appropriate

selection of unaffected relatives as possible donors for kidney transplantation. Adverse consequences

with testing, including possible difficulties with insurability and employment due to a positive diagnosis,

must be discussed.

There has been a trend for earlier diagnosis of ADPKD in patients at risk for the disease. In one cohort of

patients, for example, the age at diagnosis was significantly lower among those born between 1951 and

1974 compared to those born before 1951 (27 versus 39 years, respectively) [8].

Ultrasonographic criteria for adults Renal ultrasonography is usually used for screening

because it is safe, effective, and inexpensive. There have been no studies that adequately compared

ultrasonography with other imaging modalities for screening and diagnosis of ADPKD.

The criteria for diagnosis varies based upon whether the familial genotype is known. In the vast majority

of cases, the individual at risk for ADPKD is from a family with an unknown genotype.

At risk but unknown familial genotype We use the following ultrasonographic criteria for the

diagnosis of ADPKD for at risk individuals from families of unknown genotype:

Among individuals between 15 and 39 years of age, at least three unilateral or bilateral kidney

cysts. The specificity and positive predictive value of this criterion for individuals of this age is 100

percent. By comparison, this criteria is associated with a sensitivity of 82 and 96 percent for

individuals between 15 and 29 years, and between 30 to 39 years of age, respectively.

Among individuals 40 to 59 years of age, at least two cysts in each kidney. This finding is

associated with a sensitivity, specificity, and positive predictive value of 90, 100, and 100 percent,

respectively.

Among individuals 60 years or older, at least four cysts in each kidney. This is associated with 100

percent sensitivity and specificity.

These criteria are based upon a well-designed study of 948 individuals at risk for either PKD1 or PKD2, in

which the performance of different ultrasound criteria was evaluated among at-risk individuals who

subsequently underwent molecular genotyping [9]. A statistical resampling method

termed "bootstrapping" was used to obtain the best estimate for the accuracy of different

ultrasonographic diagnostic criteria for various age groups and also ensure that the analysis involved a

constant ratio of 85:15 of patients with PKD1 to those with PKD2. This latter feature was performed to

simulate the case mix observed in a general clinic assessing at-risk individuals of all age groups.




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This study also provided some guidance concerning the ability of specific ultrasonographic findings to

exclude the diagnosis of ADPKD among at-risk individuals from families of unknown genotype:

Among individuals 40 years of age or older, ultrasonographic evidence of zero or only one renal

cyst excludes the disease, since these findings are associated with a negative predictive value of

100 percent.

Among those 30 to 39 years of age, the disease is essentially excluded if ultrasonography reveals

the absence of any renal cysts, which is associated with a false negative rate of 2 percent. The

finding of no renal cysts with more sensitive modalities, such as CT scanning or magnetic

resonance imaging, would provide further support that the disease is not present. (See 'Other

imaging modalities' below.)

Among patients less than 30 years of age, ultrasonographic imaging is limited in its ability to help

exclude the disease. The approach to such patients is discussed in other sections in this topic

review. (See 'Other imaging modalities' below and 'Approach after equivocal ultrasound results'

below and 'Infant/child' below.)

At risk for type 1 ADPKD Some asymptomatic patients at risk for ADPKD are from families

with known and well-characterized pathogenic mutations in the PKD1 locus. In this setting, testing for the

known mutation is more definitive and may be more cost-effective than ultrasonography.

However, if genetic testing is not available or less desirable, ultrasonographic imaging may be used for

individuals who are known to be at risk for type 1 ADPKD. Among such patients, the following age-

dependent ultrasonographic criteria have been used for the diagnosis:

Among individuals between 15 and 30 years of age, at least two unilateral or bilateral cysts

Among individuals 30 to 59 years of age, two cysts in each kidney

Among individuals 60 years or older, four cysts in each kidney

These criteria were derived from an ultrasonographic study of 128 individuals at risk for PKD1 that

compared imaging findings with genotype [10]. The specificity of these criteria was found to be 100

percent for all patients at risk for type 1 ADPKD [9,11]. By comparison, the sensitivity of these findings

varies by patient age [9,11]. Among patients between 15 and 30 years of age at risk for type 1 disease,

the sensitivity of these criteria is 95 percent. The sensitivity increases to 97 to 100 percent for those older

than 30 years of age. Thus, a negative ultrasound can definitely exclude type 1 disease when the patient

is older than 30 years, although the false negative rate at age 20 is only about 4 percent [10,11].

At risk for type 2 ADPKD Some asymptomatic patients at risk for ADPKD are from families

with known and well-characterized pathogenic mutations in the PKD2 locus. In this setting, testing for the


If genetic testing is not available or less desirable, established ultrasonographic criteria are less sensitive

for patients who are known to be at risk for type 2 ADPKD. In this setting, some clinicians would use the

ultrasonographic criteria created for those at risk for ADPKD but of unknown familial genotype, as noted

above.

Other imaging modalities Because CT and magnetic resonance imaging (MRI) are more




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sensitive than ultrasonography, the sonographic criteria listed above are not applicable to these

modalities. Contrast enhanced CT scanning or MRI or heavy-weighted unenhanced T2 MR images can

reliably detect small cysts of 2 to 3 mm diameter [12].

Although not formally evaluated and only studied in small case series and reports, we believe that a

negative test (no cysts in either the kidneys or the liver) found with these techniques by 20 years of age

virtually excludes the presence of PKD, at least for type 1 disease.

Conversely, among patients with equivocal ultrasonographic studies, these techniques may demonstrate

numerous small cysts, thereby possibly precluding the need for genetic testing.

Approach after equivocal ultrasound results No formal studies have compared CT or MRI

techniques, or genetic testing among at risk adult patients with equivocal ultrasonographic results. In the

setting of an equivocal ultrasound, some clinicians prefer genetic testing, while others choose either a CT

scan or MR study with genetic testing performed if the diagnosis remains uncertain after additional

radiologic evaluation. (See 'Genetic testing' below.)

Infant/child In an infant/child at 50 percent risk for ADPKD, ultrasonography of the kidney is less

useful than in adults, with inconclusive results being noted in one-half of those at risk (particularly children

less than five years of age) [13]. As previously mentioned, we recommend NOT screening in children.However, if desired, we use renal ultrasonography for initial evaluation because it is safe and inexpensive.

The finding of large echogenic kidneys without distinct macroscopic cysts in infants is highly suggestive of

the disease. The presence of one cyst is adequate for the diagnosis in an at-risk child (0 to 15 years of

age) [13].

Genetic testing can be used when the imaging results are equivocal and/or when a definite diagnosis is

required. (See "Autosomal recessive polycystic kidney disease in children" and 'Genetic testing' below.)

Prenatal screening in the fetus at risk for ADPKD is discussed separately. (See 'Prenatal and

preimplantation genetic testing' below.)

Diagnosis of symptomatic individuals The diagnosis is easy to establish in patients withsymptomatic disease who have a family history of ADPKD. In such patients, the diagnosis is certain with

the finding of large kidneys with multiple bilateral cysts on ultrasonography or CT scanning (image 1). The

specific number of cysts per kidney detected by ultrasonography that will definitively establish the

diagnosis of ADPKD depends upon patient age and is the same as the criteria used in patients with

asymptomatic disease. (See 'Ultrasonographic criteria for adults' above.)

Affected patients may present with flank pain or renal insufficiency, and hypertension [2]. Cysts may also

be seen in the liver and pancreas. Hepatic cysts, for example, can be detected in over half of cases and

are more commonly seen in women and in patients over the age of 40 [14]. Additional manifestations

may include intracranial aneurysms, decreased urinary concentrating ability, and abdominal wall hernias

[15]. (See "Renal manifestations of autosomal dominant polycystic kidney disease" and "Extrarenalmanifestations of autosomal dominant polycystic kidney disease".)

NEGATIVE FAMILY HISTORY In up to 25 percent of cases, the clinical presentation and imaging

studies suggest a diagnosis of ADPKD [2]; however, no one else in the family is known to have the

disease.

In most such cases, the disease is inherited, but the affected parent has died without a diagnosis or is

alive with a mild form of the disease that has gone undetected. In this case, reviewing medical

information or obtaining imaging studies on the parents or other family members may prove helpful. In up




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to five percent of cases, the disease may be due to a new mutation.

In the absence of a family history, there is no definitive number of cysts and/or cyst location that provides

an unequivocal diagnosis of ADPKD. The diagnosis should be strongly suspected in the presence of

multiple and bilateral cysts (arbitrarily defined as 10 or more cysts in each kidney) in the absence of

findings suggestive of a different renal cystic disease, particularly if renal enlargement or liver cysts are

also present.

Differential diagnosis Disorders other than ADPKD must be considered in the patient without a family

history of the disease. The age of the patient, a family history of other genetic disorders, and the

presence of associated manifestations help in the differential diagnosis.

Adults and older children Acquired disorders that should be considered in adults and older

children (greater than 10 years of age) in the absence of a family history of ADPKD include:

Multiple benign simple cysts Multiple benign simple cysts are relatively common in the general

adult population and increase in number with age. Since they may be difficult to differentiate from a

mild form of ADPKD, knowledge concerning the relative prevalence of simple cysts in the general

population can help distinguish ADPKD from benign simple cysts. The prevalence of such cysts

was evaluated in a study in which renal ultrasonography was performed in 729 individuals with

normal renal function who were referred for the investigation of symptoms unrelated to the urinary

tract [16]. Ultrasonography detected at least one cyst in 0, 1.7, 11.5, and 22.1 percent of

individuals aged 15 to 29 years, 30 to 49 years, 50 to 70 years, and 70 years and above,

respectively. Bilateral renal cysts (at least one cyst in each kidney) were detected in 1, 4, and 9

percent of those aged 30 to 49, 50 to 70 years, and over 70 years, respectively.

CT and MRI are more sensitive than ultrasonography. Spiral CT detects renal cysts in

approximately 50 percent of men (mean age, 66 years) and 35 percent of women (mean age, 63

years) with a total number of cysts ranging from 1 to 10 per patient [17].

Thus, since the diagnosis of ADPKD is a possibility in some patients of the appropriate age with

multiple cysts detected via abdominal ultrasonographic imaging but without a family history of

ADPKD, the number and location of cysts may favor one diagnosis over the other:

Simple renal cysts are uncommon in patients younger than 30 years and are rarely multiple or

bilateral.

It is uncommon for patients aged 30 to 59 years to have at least two cysts in each kidney.

In patients over age 60, the finding of four or more cysts in each kidney is rarely due to

multiple simple cysts [18,19].

In problem cases, further evaluation with more sensitive imaging techniques (such as contrast-

enhanced CT scanning or MRI or heavy-weighted unenhanced T2 MRI), and the presence of

extrarenal manifestations and/or enlarged kidneys can further help establish the diagnosis of

ADPKD.

Renal ultrasonography in parents and family members can also help detect asymptomatic

ADPKD, if present [15].

Localized renal cystic disease Localized cystic disease of the kidney is an uncommon benign




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condition that can be confused with polycystic kidney disease [20-22]. In one series of 18 patients,

the age at diagnosis ranged from 24 to 83 (average 54), and none had a family history of

polycystic kidney disease [22]. Imaging studies revealed multiple cysts of various sizes separated

by normal or atrophic parenchyma involving one kidney. In contrast to polycystic kidney disease,

localized cystic disease is neither bilateral nor progressive [20].

Acquired renal cystic disease Chronic renal failure (particularly patients on maintenance

hemodialysis or peritoneal dialysis) is frequently associated with the development of multiple and

bilateral small cysts; these cysts are usually less than 0.5 cm in diameter but can be as large as 2

to 3 cm [23]. The diagnosis of acquired cystic disease in renal failure is established by

ultrasonography and/or CT scanning, although each procedure can have false negative results. A

positive test requires involvement of both kidneys with four or more cysts being present.

Acquired cystic disease is usually easily distinguished from autosomal dominant polycystic kidney

disease (ADPKD), since there is no family history of ADPKD and the kidneys are small to normal

in size with a smooth contour as opposed to usually extreme renal enlargement with a cystic

contour [23]. Rarely, however, the kidneys in those with acquired renal cystic disease may enlarge

and resemble those of ADPKD. In such cases, acquired renal cystic disease can be distinguished

by the absence of the extrarenal features of ADPKD. (See "Acquired cystic disease of the kidney

in adults" and "Extrarenal manifestations of autosomal dominant polycystic kidney disease".)

Medullary sponge kidney Medullary sponge kidney is characterized by tubular dilatation of the

collecting ducts confined to the medullary pyramids. The urographic appearance of the kidneys in

this disorder can mimic those in ADPKD, but the renal cortex is spared on CT or MRI. Autosomal

dominant inheritance has been reported in some cases [24]. (See "Medullary sponge kidney".)

Bilateral parapelvic cysts Bilateral parapelvic cysts (eg, cystic disease of the renal sinus) may

distort the renal pelvis, infundibula, and calyces, and can be confused with ADPKD on excretory

urography [25]. The lack of cysts in the cortex/medulla distinguishes this disorder from ADPKD.

Genetic disorders that should be considered in adults and older children (over the age of 10 years) in the

absence of a family history of ADPKD include the following:

Autosomal recessive polycystic kidney disease In older children or young adults, autosomal

recessive polycystic kidney disease (ARPKD) is associated with collecting duct ectasia and/or

macrocystic changes, frequently with nephrolithiasis, hypertension and/or impairment of renal

function. Patients also often present with symptoms and signs of hepatic fibrosis and portal

hypertension or ascending cholangitis, while neonates may present with enlarged echogenic

kidneys and pulmonary hypoplasia.

The ultrasonographic appearance of the kidney may not distinguish autosomal recessive PKDfrom autosomal dominant disease. Extrarenal (hepatic, pancreatic) cysts also favor the presence

of autosomal dominant disease, while portal fibrosis or signs of portal hypertension, cholangitis, or

biliary dysgenesis favor the diagnosis of autosomal recessive disease.

A careful family history and analysis of the parents is often helpful. Ultrasonography of parents of

children with autosomal recessive polycystic kidney disease will not show cysts while autosomal

dominant disease is often first discovered in a parent at the time of diagnosis in the child.

However, affected parents with autosomal dominant polycystic kidney disease under the age of 25




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to 30 may not yet have cysts detectable on ultrasonography and establishing the diagnosis may

require evaluation of the grandparents.

Genetic testing may also be helpful in some cases [26]. (See 'Genetic testing' below.)

Autosomal dominant tuberous sclerosis complex Patients with tuberous sclerosis can also

present with multiple renal cysts. The diagnosis of tuberous sclerosis is usually confirmed by

noting the presence of other features of the disease.

The diagnosis requires two major features (renal angiomyolipoma, facial angiofibromas or

forehead plaques, nontraumatic ungual or periungual fibroma, three or more hypomelanotic

macules, shagreen patch, multiple retinal nodular hamartomas, cortical tuber, subependymal

nodule, subependymal giant cell astrocytoma, cardiac rhabdomyoma, lymphangioleiomyomatosis)

or one major plus two minor features (multiple renal cysts, nonrenal hamartoma, hamartomatous

rectal polyps, retinal achromic patch, cerebral white matter radial migration tracts, bone cysts,

gingival fibromas, "confetti" skin lesions, multiple enamel pits). (See "Tuberous sclerosis complex:

Genetics, clinical features, and diagnosis" and "Renal manifestations of tuberous sclerosis and

renal angiomyolipoma".)

Autosomal dominant von Hippel-Lindau disease In addition to renal cysts, patients with von

Hippel-Lindau disease may have retinal hemangiomas, clear cell carcinomas of the kidney,

cerebellar and spinal hemangioblastomas, pheochromocytoma, endocrine pancreatic

tumors, and/or epididymal cystadenoma.

Infrequently, patients with renal cysts but without the other manifestations of the disorder may be

misdiagnosed with autosomal dominant polycystic kidney disease. The correct diagnosis is

eventually uncovered with the development of a manifestation that is unique to von Hippel-Lindau

disease, such as a hemangioblastoma. (See "Clinical features, diagnosis, and management of von

Hippel-Lindau disease".)

Autosomal dominant medullary cystic disease Unlike those with autosomal dominant polycystic

kidney disease, patients with medullary cystic disease have renal cysts at the corticomedullary

junction, small to normal size kidneys, and, particularly in type 2 disease, hyperuricemia and gout.

(See "Autosomal dominant interstitial kidney disease (medullary cystic kidney disease)", section

on 'Uromodulin-associated kidney disease (UAKD)'.)

Autosomal dominant polycystic liver disease Autosomal dominant polycystic liver disease is

distinct from polycystic kidney disease, since it is not associated with kidney involvement.

However, it may be difficult to distinguish the patient with autosomal dominant polycystic liver

disease plus simple renal cysts from the patient with ADPKD. Although family history may be

helpful, genetic testing may be required to make a definitive diagnosis. (See "Diagnosis andmanagement of cystic lesions of the liver".)

X-linked dominant orofaciodigital syndrome type I Affected females with X-linked dominant

orofaciodigital syndrome type I (OFD1) (prenatal lethality in males) may have kidneys that are

indistinguishable from autosomal dominant polycystic kidneys. Distinguishing features are

extrarenal manifestations that include oral (hyperplastic frenula, cleft tongue, cleft palate or lip and

malposed teeth), facial (broad nasal root with hypoplasia of nasal alae and malar bone) and digital

(brachy, syn, clino, campto, polydactyly) anomalies [27].




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Young children and infants In the absence of a family history of ADPKD, the differential

diagnosis of severe presentations in infants or young children (up to 10 years of life) include the following:

Autosomal recessive polycystic kidney disease As previously mentioned, imaging of the kidneys

cannot definitively distinguish autosomal recessive polycystic kidney disease from a severe early

presentation of ADPKD. Genetic testing by direct mutational analysis of the culprit genes will clarify

the diagnosis [26]. (See above and (see "Autosomal recessive polycystic kidney disease inchildren")).

Contiguous PKD1-TSC2 contiguous syndrome Deletions that inactivate both the TSC2 and

PKD1 genes are associated with severe polycystic kidney disease [28-30]. This disorder is usually

diagnosed in the first year of life and leads to ESRD at an earlier age than ADPKD alone. The

presence of manifestations unique to tuberous sclerosis helps clarify the diagnosis. Multiplex

ligation-dependent probe amplification (MLPA), which detects large gene rearrangements, may

allow for definitive diagnosis of this syndrome [31]. (See 'Genetic testing' below.)

Meckel-Gruber syndrome Meckel-Gruber syndrome includes occipital encephalocele, polycystic

kidneys, biliary dysgenesis and polydactyly. By comparison, patients with ADPKD do not have

encephalocele or polydactyly.

Other multiple malformation syndromes.

(See "Renal cystic diseases in children".)

GENETIC TESTING Among patients with equivocal imaging results and/or when a definite diagnosis

is required (such as a potential living related donor, only with informed consent), genetic testing should be

considered [32]. (See 'Differential diagnosis' above.)

Methods used to perform genetic testing are linkage or sequence analysis of DNA:

Linkage analysis uses microsatellite markers that flank the PKD1 and PKD2 genes. The techniquerequires the accurate diagnosis in an adequate number of known family members (at least four)

who are willing to be tested. Linkage analysis is therefore suitable in less than one-half of families.

Direct DNA analysis of the PKD1 and PKD2 genes is hampered by their immense size, complexity,

and allelic heterogeneity. With both genes, mutation detection rates of approximately 65 to 70

percent have been reported with denaturing high-performance liquid chromatography (DHPLC)

[33,34]. Direct sequencing is associated with rates of approximately 85 to 90 percent [35,36]. High-

throughput next generation sequencing may allow for the genetic characterization of large

populations of patients with ADPKD [37].

Whether a mutation is associated with pathogenicity is unclear since most changes are unique andmissense changes in PKD1 constitute nearly one-third of all mutations. Sequence analysis of the PKD1

and PKD2 genes is currently clinically available.

Approximately 2 to 3 percent of PKD1 mutations are large deletion mutations in which multiple exons may

be removed. Multiplex ligation-dependent probe amplification (MLPA) is a quantitative method that

detects large gene rearrangements and may allow for rapid screening for this syndrome. This method

was evaluated using the well-characterized consortium for radiological imaging studies of PKD (CRISP)

population [31]. Large gene rearrangements were detected in 4 percent of the ADPKD patients in the




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CRISP study, accounting for one-third of families without a known causative mutation. In addition, the

MLPA method allowed for the detection and characterization of six, one, and seven mutations involving

the PKD1, PKD2, and the PKD1/TSC2 region.

The choice of performing either linkage or sequence analysis largely depends upon whether the particular

technique is feasible as well as the availability of the modality.

A combined approach using both modalities may be most effective. This was shown in a study in whichgenetic linkage and direct DNA analysis was performed in patients from families with and without a

history of disease [38]. Among two prospective kidney donors with a positive family history, the use of

both linkage and DNA sequencing was required to definitively exclude the presence of ADPKD.

PRENATAL AND PREIMPLANTATION GENETIC TESTING Prenatal testing for ADPKD is clinically

available if the mutation has been identified in an affected family member or if linkage has been

established in the family. However, it is rarely considered for adult-onset conditions such as ADPKD that

do not affect intellect and have some effective therapies [39]. A possible exception may be in rare families

where severe, early-onset disease in one child suggests a significant risk of recurrence of severe disease

in a sibling. Preimplantation genetic testing has been performed in a few cases [40].

ADDITIONAL INFORMATION Additional information about PKD for patients can be obtained from:

PKD Foundation

9221 Ward Parkway, Suite 400

Kansas City, MO 64114-3367

Telephone: 800-PKD-CURE, 816-931-2600

FAX: 816-931-8655

e-mail: [email protected]

Website: www.pkdcure.org

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 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 information: Polycystic kidney disease (The Basics)")

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

SUMMARY AND RECOMMENDATIONS

Approximately 85 percent of families with autosomal dominant polycystic kidney disease (ADPKD)




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have an abnormality on chromosome 16 (PKD1 locus), while the remaining patients have a

different defect that involves a gene on chromosome 4 (the PKD2 locus). Patients with PKD2 have

a less severe phenotype than those with PKD1, but neither disorder is benign. (See 'Introduction'

above.)

Counseling should be done prior to testing among asymptomatic patients with a family history of

autosomal dominant polycystic kidney disease (ADPKD).

In children at 50 percent risk for the disease (age less than 18 years), we do NOT screen

children at risk since the adverse effects from a presymptomatic diagnosis outweigh the

current benefits. (See 'Screening and diagnosis of asymptomatic individuals' above.)

In adults at 50 percent risk for the disease (age greater than 18 years), we recommend

screening potential living related kidney donors (only with informed consent) (Grade 1A). In

other at-risk adults, the decision to screen for the disease should be based upon patient's

preferences and values after the benefits and adverse consequences of certainty concerning

the diagnosis are fully understood.

If screening is performed among asymptomatic patients with a family history of ADPKD, we

recommend imaging of the kidney (Grade 1B). Because of safety and cost, ultrasonography is

usually the initial modality.

Sonographic diagnostic criteria for the diagnosis of ADPKD for at risk individuals greater than 15

years of age who are from families of unknown genotype:

Among individuals between 15 and 39 years of age, at least three unilateral or bilateral cysts.

Among individuals 40 to 59 years of age, two cysts in each kidney.

Among individuals 60 years or older, four cysts in each kidney.

The sensitivity and specificity of these ultrasonographic findings varies by patient age. Adiscussion of these issues in patients greater than 15 years of age can be found elsewhere

(See 'Ultrasonographic criteria for adults' above.)

Some asymptomatic patients at risk for ADPKD are from families with known and well-

characterized pathogenic mutations in the PKD1 or PKD2 locus. In this setting, testing for the


(See 'Ultrasonographic criteria for adults' above.)

In children (less than 18 years of age), we recommend NOT screening. However, if performed in

an infant/child (less than 18 years of age) at risk for ADPKD, ultrasonography of the kidney is less

diagnostically useful than in adults. The finding of large echogenic kidneys without distinctmacroscopic cysts in infants is highly suggestive of the disease, while the presence of one cyst is

adequate for the diagnosis in young children. Genetic testing can be used when the imaging

results are equivocal and/or when a definite diagnosis is required. (See 'Infant/child' above.)

Among patients with symptomatic disease who have a family history of ADPKD, the specific

number of cysts per kidney that will definitively establish the diagnosis of ADPKD depends upon

patient age and is the same as the criteria used in patients with asymptomatic disease.

(See 'Diagnosis of symptomatic individuals' above.)




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In up to 25 percent of cases, the clinical presentation and imaging studies suggest a diagnosis of

ADPKD but there is no family history of the disease. In this case, reviewing medical information or

obtaining imaging studies on the parents or other family members may prove helpful. In up to five

percent of cases, the disease may be due to a new mutation. In the absence of a family history,

there is no definitive number of cysts and/or cyst location that provides an unequivocal diagnosis

of ADPKD. (See 'Negative family history' above.)

Disorders other than ADPKD must be considered in a patient without a family history of the

disease. The age of the patient, a family history of other genetic disorders, and the presence of

associated manifestations help in the differential diagnosis. (See 'Differential diagnosis' above.)

Genetic testing, which can be performed by linkage or sequence analysis, can be used when the

imaging results are equivocal and/or when a definitive diagnosis is required. (See 'Genetic testing'

above.)

Although prenatal testing is clinically available if the mutation has been identified in an affected

family member or if linkage has been established in the family, it is rarely considered for adult-

onset conditions such as ADPKD. (See 'Prenatal and preimplantation genetic testing' above.)

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REFERENCES

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176:843.23. Levine E. Acquired cystic kidney disease. Radiol Clin North Am 1996; 34:947.

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polycystic kidney disease through targeted resequencing. J Am Soc Nephrol 2012; 23:915.

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type 1. Mol Hum Reprod 2005; 11:65.

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GRAPHICS

CT scan showing polycystic kidney disease

Abdominal CT scan in a patient with polycystic kidney disease

shows extensive cysts in both kidneys; the cysts have almost

completely replaced the renal parenchyma.Courtesy of Jonathan Kruskal, MD, PhD.




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Diagnosis of and Screening for Autosomal Dominant Polycystic Kidney Disease

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