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Polycystic Kidney Disease: Autosomal Dominant Type Harold Chen Contents Synonyms and Related disorders .................... 1 Genetics/Basic Defects ................................ 1 Clinical Features ....................................... 3 Diagnostic Investigations ............................. 6 Genetic Counseling .................................... 7 References .............................................. 9 Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of polycystic kidney disease with an estimated incidence of approximately 1/4001/1,000 individuals world- wide. It roughly accounts for 10 % of patients with chronic renal failure requiring hemodialysis or transplantation (Arnaout 2001). Synonyms and Related disorders Adult type; Polycystic kidney disease Genetics/Basic Defects 1. Inheritance: 1. Autosomal dominant with almost complete penetrance 2. Negative family history in 40 % of cases 2. Genetically heterogeneous with at least three different genes now known to cause ADPKD. All three types of ADPKD present with an identical prole of extrarenal manifestations (including liver cysts and aneurysms) (Wilson 2004): 1. Type I (8590 % of cases): caused by muta- tions in PKD1 gene, which is: 1. Mapped on chromosome 16p13.3. 2. The most severe form with a lower median survival and a higher risk of progressing to end-stage renal disease. H. Chen (*) Medical Genetics, Shriners Hospitals for Children, Shreveport, LA, USA Perinatal and Clinical Genetics, Department of Pediatrics, LSU Health Sciences Center, Shreveport, LA, USA e-mail: [email protected] # Springer Science+Business Media New York 2016 H. Chen (ed.), Atlas of Genetic Diagnosis and Counseling, DOI 10.1007/978-1-4614-6430-3_193-2 1

Polycystic Kidney Disease: Autosomal Dominant Type · Polycystic Kidney Disease: Autosomal Dominant Type Harold Chen Contents Synonyms and Related disorders ..... 1 Genetics/Basic

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Page 1: Polycystic Kidney Disease: Autosomal Dominant Type · Polycystic Kidney Disease: Autosomal Dominant Type Harold Chen Contents Synonyms and Related disorders ..... 1 Genetics/Basic

Polycystic Kidney Disease: AutosomalDominant Type

Harold Chen

ContentsSynonyms and Related disorders . . . . . . . . . . . . . . . . . . . . 1

Genetics/Basic Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Diagnostic Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Genetic Counseling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Autosomal dominant polycystic kidney disease(ADPKD) is the most common form of polycystickidney disease with an estimated incidence ofapproximately 1/400–1/1,000 individuals world-wide. It roughly accounts for 10 % of patientswith chronic renal failure requiring hemodialysisor transplantation (Arnaout 2001).

Synonyms and Related disorders

Adult type; Polycystic kidney disease

Genetics/Basic Defects

1. Inheritance:1. Autosomal dominant with almost complete

penetrance2. Negative family history in 40 % of cases

2. Genetically heterogeneous with at least threedifferent genes now known to cause ADPKD.All three types of ADPKD present with anidentical profile of extrarenal manifestations(including liver cysts and aneurysms) (Wilson2004):1. Type I (85–90 % of cases): caused by muta-

tions in PKD1 gene, which is:1. Mapped on chromosome 16p13.3.2. The most severe form with a lower

median survival and a higher risk ofprogressing to end-stage renal disease.

H. Chen (*)Medical Genetics, Shriners Hospitals for Children,Shreveport, LA, USA

Perinatal and Clinical Genetics, Department of Pediatrics,LSU Health Sciences Center, Shreveport, LA, USAe-mail: [email protected]

# Springer Science+Business Media New York 2016H. Chen (ed.), Atlas of Genetic Diagnosis and Counseling,DOI 10.1007/978-1-4614-6430-3_193-2

1

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3. Closely linked to TSC2, a gene respon-sible for a major form of tuberoussclerosis.

4. ADPKD1 is an inherited disorder thathas led to the discovery of a novel pro-tein, polycystin. Polycystin, a 460 kdprotein with a host of domains implicat-ing a potential role in cell-cell and cell-matrix regulation, is encoded by a 52 kbgene with a 14 kb mRNA (Grantham1996). ADPKD1 is caused by mutatedDNA that encodes an abnormal form ofpolycystin.

5. Highly variable severity of renal cysticdisease (Rossetti et al. 2002a).

2. Type II (most of the remaining cases):caused by mutations in PKD2 gene, whichis:1. Mapped on chromosome 4q13-q23

(Kimberling et al. 1993).2. Identified by positional cloning.3. Producing milder disease but otherwise

phenotypically identical with the PKD1disease.

4. PKD2 protein is also large (110 kd) andis thought to interact with polycystin(Grantham 1996).

5. Although PKD2 is clinically milder thanPKD1, it has a deleterious impact onoverall life expectancy and cannot beregarded as a benign disorder (Hateboeret al. 1999).

3. In the vast majority of cases, the disease iscaused by mutations in PKD1 or PKD2 andappears to be recessive at the cellular level.Somatic second hits in the normal allele ofcells containing the germline mutation ini-tiate or accelerate formation of cysts. Theintrinsically high frequency of somatic sec-ond hits in epithelia appears to be sufficientto explain the frequent occurrence ofsomatic second hits in the disease-causinggenes (Arnaout 2001).

4. A small number of familial cases reported tobe unlinked to both the PKD1 and PKD2loci, suggesting the existence of at least onemore proposed gene (PKD3) which has not

been identified (Daoust et al. 1995; Arizaet al. 1997).

5. Patients with mutations in both the PKD1and PKD2 genes (transheterozygotes) (Peiet al. 2001) have a more severe clinicalcourse than those with mutations in onlyone of the genes.

3. Mechanism of cyst formation: somatic second-hit model (Wilson 2004):1. A germline mutation in one PKD allele in

all cells in ADPKD2. A random somatic mutation (second hit)

occurring in the normal allele causingincreased cell proliferation, leading to cystformation

4. Molecular basis of ADPKD (Rossettiet al. 2002b):1. Protein products of the disease gene

forming a macromolecular signaling struc-ture, the polycystin complex, that regulatesfundamental aspects of renal epithelialdevelopment and cell biology

2. Protein products of PKD1 and PKD2(polycystin-1 and polycystin-2),respectively:1. Share sequence homology2. May form components of a receptor/

channel complex3. Polycstin-1:

1. Predicted to have a receptor-likestructure

2. May be involved in cell-cell/matrixinteractions

3. May have a regulatory role over apolycystin channel

4. Polycystin-2:1. Similar to and functioning as an ion

channel subunit2. Causes nonselective cation permeability

5. Basic defect in ADPKD: could be inpolycystin-regulated intracellular Ca++

levels5. Molecular basis of other polycystic kidney dis-

ease (Wilson 2004):1. Autosomal recessive polycystic kidney dis-

ease (please see the chapter “▶ PolycysticKidney Disease, Autosomal RecessiveType”):

2 H. Chen

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1. Caused by mutation in PKHD1 loss offunctional fibrocystin

2. Fibrocystin: a receptor-like membraneprotein with putative extracellular matrixinteraction domains as well as intracel-lular signaling sites

2. Juvenile nephronophthisis:1. Caused by mutation in NPH1 loss of

functional nephrocystin2. Nephrocystin: an intracellular protein

that interacts with the focal adhesioncomplex, the cilium, and tyrosine signal-ing molecules

6. Disease characteristics:1. Principal ductal organs with cyst formation:

1. Kidneys2. Liver

2. Consequences of cyst enlargement:1. Progressive destruction of normal renal

tissue2. End-stage renal failure in >50 % of

patients by age 603. Systemic involvement:

1. Arterial hypertension developing earlyand observed in >50 % of patients

2. Vascular aneurysms3. Cardiac valve defects4. Colonic diverticula

Clinical Features

1. Autosomal dominant polycystic kidneydisease:1. Presenting in the fetus or newborn is rare

(Edwards and Baldinger 1989).2. First symptoms of the disease occur usu-

ally in the third or fourth decade of life(Wolyniec et al. 2008).

2. Intrafamilial and interfamilial variability inthe onset, phenotype, and progression of thedisease:1. Due to genetic heterogeneity:

1. More common PKD1 (accounting forapproximately 85 % of cases associ-ated with more severe disease)

2. Evidence of significant intrafamilialphenotypic variation suggesting

modifying factors (such as theangiotensin-converting enzyme inser-tion/deletion polymorphism) as well asenvironmental factors that influence theclinical course

3. Association of the position of thePKD1 mutation with earlier end-stagerenal disease

2. Age of onset:1. Presenting at any age2. Generally presenting in the fourth and

fifth decades of life3. Occasionally presenting in the fetal or

neonatal period3. Onset of disease in the childhood in children

who carry PKD1 gene:1. Frequency of children with renal cysts

detectable by ultrasound:1. Sixty percent by 5 years of age2. Seventy-five to eighty percent among

children aged 5–18 years2. Number of renal cysts at 11 years:

1. One to ten in 60 % of children2. More than ten cysts in 40 % of children

4. Age at the time of diagnosis and progressionof the disease:1. Diagnosis in utero or in the first year of life

(intrauterine or infantile onset)1. Manifesting unusually severe disease2. End-stage renal disease during child-

hood in 18 % of cases2. Diagnosis after the first year of life:

1. Increase in the number of cysts over amean interval of 3.7 years

2. Systolic hypertension in 9 % of cases3. None with decreased renal function

5. Renal manifestations (Fick and Gabow 1994;Fick et al. 1994):1. Development of bilateral renal cysts:

1. Primary renal manifestation2. Leading to functional changes

(impaired renal concentrating capacity,hypertension)

3. Leading to various clinicalmanifestations

2. Flank or back pain (about 60 %)3. Acute pain:

1. Infected cyst

Polycystic Kidney Disease: Autosomal Dominant Type 3

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2. Ruptured cyst (associated with grosshematuria)

3. Nephrolithiasis (20–36 %) (Torreset al. 1993)

4. Urinary tract infection (40–68 %)5. Hematuria6. Mild proteinuria7. End-stage renal disease

6. Extrarenal manifestations (Fick and Gabow1994; Perrone 1997; Luciano and Dahl2014):1. Liver involvement (Chauvear et al. 2000):

1. Most common extrarenal manifestation2. Liver cysts uncommon before 16 years

of age3. Liver cysts observed in about 75 % of

patients older than 60 years4. No liver symptoms in most patients

with ADPKD5. Occasionally encountered liver

changes:1. Congenital hepatic fibrosis2. Segmental dilation of the biliary

tract6. Liver cysts responsible for most of the

hepatic complications7. Acute complications (Chauvear

et al. 2000):1. Cyst infection2. Cyst hemorrhage3. Cyst rupture4. Cyst torsion

8. Chronic complications related to pro-gressive increase of the polycysticliver (Chauvear et al. 2000):1. Abdominal mass2. Ascites3. Hepatic venous outflow obstruction

(Budd-Chiari syndrome)4. Portal hypertension with variceal

bleeding5. Inferior vena cava compression6. Bile duct compression7. Jaundice

9. Intrahepatic biliary cysts:1. More common in women2. Exacerbated by pregnancy

2. Unrelated to liver cysts (Chauvearet al. 2000):1. Congenital hepatic fibrosis or biliary

fibroadenomatosis, focal or diffuse2. Idiopathic dilation of the intra- or extra-

hepatic biliary tract (Caroli syndrome)3. Cholangiocarcinoma

3. Other rare cystic involvement (Ficket al. 1994):1. Pancreatic cysts (10 %) (Kim

et al. 2016)2. Arachnoid cysts (5 %)3. Ovarian cysts

4. Cardiovascular manifestations notuncommon:1. Intracranial berry aneurysms (5–10 %)2. Dolichoectatic arteries3. Aortic root dilatation4. Dissections of intracerebral, coronary,

thoracic, iliac, aortic, and splenic arter-ies reported

5. Cardiac valve defects5. Other noncystic involvement

(Mikolajczyk et al. 2016):1. Colonic diverticula (80 % of patients

with end-stage renal disease)2. Hernias (25 %)3. Large bile duct abnormalities

7. Clinical course in children:1. Clinical spectrum ranging from severe

neonatal manifestations mimicking auto-somal recessive polycystic kidney diseaseto renal cysts noted on ultrasound inasymptomatic children

2. Diagnosis made in utero by ultrasound:massively enlarged cystic kidneys

3. Newborn presenting with Potter pheno-type and death from pulmonaryhypoplasia

4. Newborn with large abdominal masses5. After neonatal period:

1. Hypertension2. Abdominal pain3. Palpable abdominal mass4. Hematuria5. Renal insufficiency, only rarely6. Renal infections

4 H. Chen

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6. Rare extrarenal manifestations:1. Liver cysts2. Cerebral vessel aneurysms

7. Prognosis:1. Severe symptoms in neonatal or infan-

tile cases2. Milder symptoms in late childhood

cases8. The progression of ADPKD clearly occurs in

childhood and manifests as an increase in cystnumber and renal size (Fick-Brosnahanet al. 2001).

9. There was a significant relationship betweenthe severity of the renal structural involve-ment and the frequency of flank and backpain, hypertension, and impaired renal con-centrating capacity. There was progression ofthe disease, reflected by an increase in cystnumber and an increase in the frequency ofpain and hypertension. However, glomerularfiltration rate (GFR) remained stable in allchildren (Fick et al. 1994).

10. Genotype-phenotype correlation in childrenwith ADPKD (Fencl et al. 2009):1. PKD1 children have more and larger renal

cysts, larger kidneys, and higher ambula-tory blood pressure than do PKD2children.

2. Renal cysts and enlarged kidneys detectedprenatally are highly specific for childrenwith PKD1.

11. Reproductive issues for adults with ADPKD(Vora et al. 2008):1. Men with ADPKD:

1. Necrospermia2. Immotile sperm3. Seminal vesicle cysts4. Ejaculatory duct cysts

2. Female fertility is not affected:1. Affected women with ADPKD and nor-

mal renal function have a high rate ofsuccessful uncomplicated pregnancies.

2. Pregnant women with ADPKD withcompromised kidney function shouldbe monitored carefully for the develop-ment of hypertension andpreeclampsia.

12. Risk factors precipitating faster progressionof the disease:1. The PKD-1 gene2. Male gender3. Earlier onset of symptoms:

1. Renal enlargement2. Hematuria3. Proteinuria4. Incipient renal failure5. Hypertension

4. Having >10 renal cysts before age12 years

5. Having blood pressures above the 75thpercentile for age, height, and gender

6. Polycystic liver disease:1. Frequently associated with autosomal

dominant polycystic kidney disease2. Develops later than renal cysts3. Develops earlier and more severe in

women than in men13. End-stage renal disease:

1. The most feared renal complication ofADPKD

2. Occurs in more than half of patients by theseventh decade of life

14. Differential diagnosis (Wolyniec et al. 2008):1. Autosomal recessive polycystic kidney

disease: manifests advanced renal insuffi-ciency present already in childhood orearly youth (see the chapter “▶AutosomalRecessive Polycystic Kidney Disease”)

2. ▶Tuberous Sclerosis Complex (see thechapter):1. Cysts in the kidneys observed in 20 %

of patients with tuberous sclerosiscomplex

2. Associated with characteristic skin andneurological symptoms

3. ▶Von Hippel-Lindau Disease (see thechapter)

4. Medullary cystic kidney disease:1. Most commonly occurs as juvenile

nephronophthisis2. Associated with chronic renal failure in

childhood5. ▶Oral-Facial-Digital Syndrome (see the

chapter)6. Multicystic renal dysplasia in adults:

Polycystic Kidney Disease: Autosomal Dominant Type 5

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1. Usually a unilateral disorder2. Frequent presence of calcification in

the cyst walls and abnormal structureof parenchyma between the cysts visi-ble on ultrasound

7. Medullary sponge kidney: lithiasis andnephrocalcinosis commonly observed inthe course of the disease

8. Acquired cystic kidney disease15. Differential features of ARPKD and ADPKD

(Verghese and Miyashita 2014):1. ARPKD:

1. Mode of inheritance: autosomalrecessive.

2. Location of cysts: Cysts are dilation ofrenal collecting ducts.

3. Gross appearance: reniform shapemaintained; multiple minute cysticspaces throughout the capsular sur-faces. Cut sections of the kidney showsubcapsular extensions of radially ori-ented cylindrical or fusiform ectaticspaces from the medulla to the cortex.

4. Age of presentation: most often in theneonatal period or childhood.

5. Frequency: 1 in 20,000 live births.6. Extrarenal features: can occur in neo-

nates; congenital hepatic fibrosis in allpatients; manifestations ofoligohydramnios, such as pulmonaryinsufficiency; Potter facies, club foot,and so forth

7. Renal prognosis: Fetuses with severerenal failure, oligohydramnios, andpulmonary hypoplasia often die of pul-monary complications. Patients withless severe renal manifestations whosurvive the neonatal period have a50 % chance of developing end-stagerenal disease (ESRD) by age 10 years.

2. ADPKD:1. Mode of inheritance: autosomal

dominant2. Location of cysts: Cysts develop any-

where along the nephron.3. Gross appearance: loss of reniform

shape of kidney; numerous, large,

round nodules/cysts of varying sizeson the external surface of the kidneyand randomly distributed through theentire parenchyma of the kidney.

4. Age of presentation: Most often ini-tially presents in adults aged 20–40years, but increasingly there are reportsof ADPKD presenting in childhood andeven in utero.

5. Frequency: one case in 400–1000population.

6. Extrarenal features: does not occur inneonates. Congenital hepatic fibrosisand portal hypertension are very rare.Manifestations of oligohydramnios arerare. Includes hepatic cysts, pancreaticcysts found exclusively in patients withPKD1, cerebral vessel aneurysms,mitral valve prolapse, endocardialfibroelastosis, increased left ventricularmass with diastolic dysfunction even innormotensive children, ovarian cysts.

7. Renal prognosis: Chances of ESRD are2 % in those <40 years of age andincrease to 50 % by the seventh decadeof life.

Diagnostic Investigations

1. Urinalysis:1. Hematuria2. Mild proteinuria3. Evidence of infection

2. Sonography:1. Prenatal presentation:

1. Large hyperechogenic kidneys: the mostconsistent renal ultrasonographic find-ings in children (Fick et al. 1993)

2. Variable size3. Mixtures of small and large cysts4. Exceptionally uncommon

oligohydramnios2. Postnatal presentation: invariably large

cysts3. Renal ultrasound and IVP:

1. Enlarged kidneys

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2. Macrocysts and distortion of the collectingsystem

4. Age at clinical onset and at ultrasonographicdetection of adult polycystic kidney disease(Bear et al. 1984): The probability of ultraso-nographic detection of asymptomatic APKD isestimated as 0.222, 0.657, and 0.855 at age5, 15, and 25 years, respectively.

5. CT scan and/or MRI for renal, hepatic (Guptaet al. 1999), pancreatic, and ovarian cysts

6. CT scan and/or MRI angiography for intracra-nial aneurysm

7. Renal function tests8. Renal ultrasound to assess carrier status:

1. A painless and relatively noninvasiveprocedure

2. Detection rate in asymptomatic subjectsfrom families with known ADPKD:1. Twenty-two percent of cases in the first

decade2. Sixty-six percent of cases by the second

decade3. Eighty-six percent by age 25

9. Molecular diagnosis (Harris and Rossetti2010):1. Diagnosis of ADPKD before the onset of

symptoms is usually performed using renalimaging by either ultrasonography, CT, orMRI. In general, these modalities are reli-able for the diagnosis of ADPKD in olderindividuals.

2. However, molecular testing can be valuablewhen a definite diagnosis is required inyoung individuals, in individuals with anegative family history of ADPKD, and tofacilitate preimplantation genetic diagnosis.

3. Although linkage-based diagnosticapproaches are feasible in large families,direct mutation screening is generallymore applicable.

4. Identification and characterization of PKD1and PKD2 provided an opportunity formutation-based molecular diagnostics tobe used for ADPKD. Mutations in PKD1account for about 85 % of cases and causemore severe disease than mutationsin PKD2.

5. As ADPKD displays a high level of allelicheterogeneity, complete screening of bothgenes is required.

6. Consequently, such screening approachesare expensive. Screening of individualswith ADPKD detects mutations in up to91 % of cases.

7. However, only about 65 % of patients havedefinite mutations, with about 26 % havingnondefinite changes that require furtherevaluation.

8. Collation of known variants in the ADPKDmutation database and systematic scoring ofnondefinite variants is increasing the diag-nostic value of molecular screening.

9. Mutation analysis of the entire PKD1 gene(Rossetti et al. 2001): The majority ofchanges were predicted to truncate the pro-tein through nonsense mutations (32 %),insertions or deletions (29.6 %), or splicingchanges (6.2 %) (Rossetti et al. 2001).

10. A complete mutation screen of theADPKD genes by denaturing high-performance liquid chromatography(DHPLC) (Rossetti et al. 2002b).

11. Diagnosis of autosomal dominant poly-cystic kidney disease using efficientPKD1 and PKD2 targeted next-generationsequencing (Trujillano et al. 2014).

12. Prenatal forms of autosomal dominantpolycystic kidney disease (ADPKD) arerare but can be recurrent in some families,suggesting a common genetic modifyingbackground. Few patients have beenreported carrying, in addition to the famil-ial mutation, variation(s) in polycystic kid-ney disease 1 (PKD1) orHNF1 homeoboxB (HNF1B), inherited from the unaffectedparent, or biallelic polycystic kidney andhepatic disease 1 (PKHD1) mutations(Audrézet et al. 2016).

Genetic Counseling

1. Recurrence risk:1. Patient’s sib:

Polycystic Kidney Disease: Autosomal Dominant Type 7

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1. Not increased in de novo case2. Fifty percent if one of the parent is

affected2. Patient’s offspring:

1. Fifty percent risk of acquiring thedisease

2. Both sexes of offspring affected equally2. Carrier testing for family members at risk:

1. Ultrasound and radiography2. Molecular mutation analysis of PKD1 and

PKD2 genes3. Prenatal diagnosis:

1. Prenatal ultrasonography:1. Enlarged kidneys (hyperechogenic) with

or without cysts: the most common fetalfindings.

2. Absence of urine in the bladder.3. May not be evident until the third

trimester.4. Evidence of uteroplacental insufficiency

(Vora et al. 2008):1. Intrauterine growth restriction2. Oligohydramnios

5. Though a highly penetrant disease, dueto varied clinical expression and the typ-ical late onset of symptoms,reproductive-aged women may notknow their carrier status. Fetal US find-ings of ADPKD prompted maternaldiagnosis of ADPKD (Euser et al. 2015).

2. Molecular mutation analysis of PKD1 andPKD2 genes on fetal DNA obtained fromamniocentesis or CVS, provided the muta-tion has been identified in the affected fam-ily members or linkage has been establishedin the family.

3. Preimplantation genetic diagnosis possible,provided the mutation has been identifiedpreviously (Harris and Torres 2015).Genetic testing offers the chance ofperforming prenatal or preimplantation test-ing of embryos in families with severe casesof the disease (Balcells and Criach 2011).

4. Management (Harris and Torres 2015):1. No treatment currently directed at the dis-

ease process.2. Monitoring of presymptomatic patients

with ADPKD:

1. Monitor blood pressure2. Test renal function3. Advantages:

1. Prevent or control hypertension2. Prevent or control infection3. Identify potential kidney donors from

among the family4. Offer advice on reproduction5. Provide prenatal diagnosis

3. Identification of alterable factors such ashypertension, number of pregnancies, andrecurrent urinary tract infections providesthe clinician with the opportunity to modifythese factors and improve the managementof patients with autosomal dominant poly-cystic kidney disease (Gabow et al. 1992).

4. In patients with ADPKD, an effort shouldbe made to keep the arterial blood pressurebelow 120/80 mmHg. In patients at highrisk of progression whose renal function isstill intact (eGFR > 60 mL/min), strictblood pressure control (<110/75 mmHg)is indicated and possibly V2R blockadewith tolvaptan as well (Kühn and Walz2015).

5. Treatment of polycystic kidney disease:1. Narcotic analgesics for pain2. Antibiotics for infection3. Treatment of nephrolithiasis:

1. Potassium citrate for uric acid lithia-sis, hypocitric calcium oxalatenephrolithiasis, and distal acidifica-tion defects

2. Extracorporeal shock wavelithotripsy

3. Percutaneous nephrostolithotomy4. Needle aspiration of dominant cysts5. Laparoscopic management of renal cys-

tic disease (Hemal 2001): a highly effec-tive, safe, and minimally invasivealternative to open surgery andantegrade or retrograde endoscopicprocedures

6. Open renal cyst decortication7. Therapeutic intervention aimed at

slowing the progression of renal failure:1. Control of hypertension2. Control of hyperlipidemia

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3. Dietary protein restriction4. Control of acidosis5. Prevention of hyperphosphatemia

8. Renal dialysis9. Renal transplantation for end-stage renal

disease6. Treatment of massive polycystic liver dis-

ease (Chauvear et al. 2000):1. Aspiration of cyst fluid.2. Stenting.3. Cyst fenestration.4. Liver resection.5. Liver transplantation.6. Selected patients with severe symptoms

benefit from liver resection and exten-sive fenestration with acceptable mor-bidity and mortality. Total hepatectomyand orthotopic liver transplantation maybe considered for patients with severeadult polycystic liver disease (Chen2000).

7. Treatment for nephrolithiasis: extracorpo-real shock wave lithotripsy and percutane-ous nephrostolithotomy (Torres et al. 1993).

8. Treatment of cerebral aneurysms (Pirsonet al. 2002):1. Asymptomatic aneurysm:

1. Observation and yearly follow-up2. Surgery for enlarging aneurysm

2. Ruptured or symptomatic aneurysm:surgical clipping at its neck

9. Management of aortic dissection:1. Aortic root dilatation:

1. Yearly follow-up2. Strict blood pressure control with

β-blockade2. Surgery (replacement of the aorta) for

aortic root greater than 55–60 mm10. Multidrug approach in management of

patients with ADPKD (Ecder 2016):1. A multidrug approach is needed in the

management of patients with ADPKD,not only to slow the progression ofrenal disease but also to decrease thecardiovascular complications, themajor cause of morbidity and mortalityin these patients (Ecder 2013).

2. Aggressive blood pressure control withan ACE inhibitor or an angiotensinreceptor blocker forms the basis of thistherapy.

3. The addition of tolvaptan (Gansevoortet al. 2016) is expected to provide sup-plementary benefit in decreasing thedecline of renal function in thesepatients.

4. Statins would have beneficial effects onslowing the progression of ADPKD.

References

Ariza, M., Alvarez, V., Marin, R., et al. (1997). A familywith a milder form of adult dominant polycystic kidneydisease not linked to the PKD1 (16p) or PKD2(4q) genes. Journal of Medical Genetics, 34, 587–589.

Arnaout, M. A. (2001). Molecular genetics and pathogen-esis of autosomal dominant polycystic kidney disease.Annual Review of Medicine, 52, 93–123.

Audrézet, M. P., Corbiere, C., Lebbah, S., et al. (2016).Comprehensive PKD1 and PKD2 mutation analysis inprenatal autosomal dominant polycystic kidney dis-ease. Journal of American Society of Nephrology, 27,722–729.

Balcells, R. T., & Criach, E. A. (2011). Molecular diagno-sis of autosomal dominant polycystic kidney disease.Nefrología, 31, 35–43.

Bear, J. C., McManamon, P., Morgan, J., et al. (1984). Ageat clinical onset and at ultrasonographic diction of adultpolycystic kidney disease: Data for genetic counselling.American Journal of Medical Genetics, 18, 45–53.

Chauvear, D., Fakhouri, F., & Grünfeld, J.-P. (2000). Liverinvolvement in autosomal-dominant polycystic kidneydisease: Therapeutic dilemma. Journal of the AmericanSociety of Nephrology, 11, 1767–1775.

Chen, M. F. (2000). Surgery for adult polycystic liverdisease. Journal of Gastroenterology and Hepatology,15, 1239–1242.

Daoust, M. C., Reynolds, D. M., Biche, T. D. G.,et al. (1995). Evidence for a third genetic locus forautosomal dominant polycystic kidney disease. Geno-mics, 25, 733–736.

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Fig. 1 (a–d) A lady (a) with autosomal dominant poly-cystic kidney disease and with family history of multipleaffected family members. Her liver was markedly enlargedas shown by a pencil mark on the patient’s photo. Theultrasonography of the kidneys showed numerous cystswith minimal residual normal appearing cortex. The rightkidney (b) measured 11 cm, with the largest cyst measuring2.9 cm. The left kidney measured 13.3 cm in length, with

the largest cyst measuring 3.8 cm (image not shown). Theabdominal CT scan (c) showed marked hepatomegalywhich occupies the entire abdomen. Numerous hepaticcysts and renal cysts were evident. Numerous cysts ofdifferent sizes were also detected in her brother’s enlargedkidneys by ultrasonography (the left kidney is shown hereon image (d))

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Fig. 2 (a–c) Three CT scans of an adult patient with polycystic kidney disease with and without contrast showingmultiple cysts in the kidneys and liver

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Fig. 3 Appearance of thegross (a) and cut section (b)of a kidney (745 g)surgically removed from a43-year-old female withautosomal dominantpolycystic kidney disease

Fig. 4 Multiple hepatic cysts of a patient with autosomaldominant polycystic kidney disease

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