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  • 12/31/15, 4:40 PMPolycystic Kidney Disease, Autosomal Dominant - GeneReviews - NCBI Bookshelf

    Page 1 of 51http://www.ncbi.nlm.nih.gov/books/NBK1246/?report=printable

    Clinical characteristics.

    Diagnosis/testing.

    Management.

    NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

    Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle;1993-2015.

    Polycystic Kidney Disease, Autosomal DominantSynonym: ADPKD

    Peter C Harris, PhDDivision of Nephrology and HypertensionMayo ClinicRochester, Minnesotaharris.peter@mayo.edu

    Vicente E Torres, MDDivision of Nephrology and HypertensionMayo ClinicRochester, Minnesotatorres.vicente@mayo.edu

    Initial Posting: January 10, 2002; Last Update: June 11, 2015.

    Summary

    Autosomal dominant polycystic kidney disease (ADPKD) is generally a late-onsetmultisystem disorder characterized by: bilateral renal cysts; cysts in other organs including the liver, seminal vesicles,pancreas, and arachnoid membrane; vascular abnormalities including intracranial aneurysms, dilatation of the aorticroot, and dissection of the thoracic aorta; mitral valve prolapse; and abdominal wall hernias. Renal manifestationsinclude hypertension, renal pain, and renal insufficiency. Approximately 50% of individuals with ADPKD have end-stage renal disease (ESRD) by age 60 years. The prevalence of liver cysts, the most common extrarenal manifestationof ADPKD, increases with age and may have been underestimated by ultrasound studies. The prevalence ofintracranial aneurysms is higher in those with a positive family history of aneurysms or subarachnoid hemorrhage(22%) than in those without such a family history (6%). Mitral valve prolapse, the most common valvularabnormality, occurs in up to 25% of affected individuals. Substantial variability in severity of renal disease and otherextrarenal manifestations occurs even within the same family.

    The diagnosis of ADPKD is established primarily by imaging studies of the kidneys. Inapproximately 85% of individuals with ADPKD, pathogenic variants in PKD1 are causative; in approximately 15%pathogenic variants in PKD2 are causative.

    Treatment of manifestations: Treatment for hypertension may include ACE inhibitors or angiotensin IIreceptor blockers and diet modification. Conservative treatment of flank pain includes nonopioid agents, tricyclicantidepressants, narcotic analgesics, and splanchnic nerve blockade. More aggressive treatments include cystdecompression with cyst aspiration and sclerosis, laparoscopic or surgical cyst fenestration, and renal denervation.Cyst hemorrhage and/or gross hematuria are usually self-limited. Treatment of nephrolithiasis is standard. Treatmentof cyst infections is difficult, with a high failure rate. Therapeutic agents of choice may include trimethoprim-sulfamethoxazole, fluoroquinolones, clindamycin, vancomycin, and metronidazole. The diagnosis of malignancyrequires a high index of suspicion. Therapeutic interventions aimed at slowing the progression of ESRD in ADPKDinclude control of hypertension and hyperlipidemia, dietary protein restriction, control of acidosis, and prevention ofhyperphosphatemia. Most individuals with polycystic liver disease have no symptoms and require no treatment. Themainstay of therapy for ruptured or symptomatic intracranial aneurysm is surgical clipping of the ruptured aneurysm

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  • 12/31/15, 4:40 PMPolycystic Kidney Disease, Autosomal Dominant - GeneReviews - NCBI Bookshelf

    Page 2 of 51http://www.ncbi.nlm.nih.gov/books/NBK1246/?report=printable

    Genetic counseling.

    at its neck; however, for some individuals, endovascular treatment with detachable platinum coils may be indicated.Thoracic aortic replacement is indicated when the aortic root diameter exceeds established size.

    Surveillance: Early blood pressure monitoring starting in childhood; there is insufficient evidence for recommendingscreening for renal cell carcinoma in asymptomatic individuals; MRI screening for intracranial aneurysms in thosedetermined to be at high risk; screening echocardiography in those with a heart murmur and those with a familyhistory of a first-degree relative with a thoracic aortic dissection.

    Agents/circumstances to avoid: Long-term administration of nephrotoxic agents, caffeine in large amounts (whichmay promote renal cyst growth), use of estrogens and possibly progestogens by individuals with severe polycysticliver disease, and smoking.

    Evaluation of relatives at risk: Testing of adult relatives at risk permits early detection and treatment of complicationsand associated disorders.

    Pregnancy management: Pregnant women with ADPKD should be monitored for the development of hypertension,urinary tract infections, oligohydramnios, and preeclampsia; the fetus should be monitored for intrauterine fetalgrowth restriction and fetal kidney anomalies, including cysts, enlarged size, and atypical echogenicity.

    ADPKD is inherited in an autosomal dominant manner. About 95% of individuals with ADPKDhave an affected parent; at least 10% of families can be traced to de novo mutation. Each child of an affectedindividual has a 50% chance of inheriting the pathogenic variant. If the pathogenic variant has been identified in anaffected family member prenatal testing for pregnancies at increased risk may be available from a clinical laboratorythat offers either testing of this gene or custom prenatal testing. Preimplantation genetic diagnosis (PGD) may be anoption for some families in which the pathogenic variant has been identified and is increasing being employed byfamilies at risk for ADPKD

    Diagnosis

    Clinical Diagnosis

    Autosomal dominant polycystic kidney disease (ADPKD) is a multisystem disorder characterized by the following:

    Bilateral renal cysts (see Renal Cysts)

    Cysts in other organs including the liver, seminal vesicles, pancreas, and arachnoid membrane

    Extrarenal abnormalities including intracranial aneurysms and dolichoectasias, dilatation of the aortic rootand dissection of the thoracic aorta, mitral valve prolapse, and abdominal wall hernias

    The absence of manifestations suggestive of a different renal cystic disease

    In an individual with a positive family history of ADPKD

    Enlargement of the kidneys or liver on physical examination is highly suggestive of the diagnosis.

    The presence of hypertension, mitral valve prolapse, or abdominal wall hernia is suggestive of the diagnosis.

    Note: Definitive diagnosis relies on imaging and/or molecular genetic testing.

    In the absence of a family history of ADPKD. The (1) presence of bilateral renal enlargement and cysts with or

    http://www.ncbi.nlm.nih.gov/books/NBK1246/?report=printable#pkd-ad.Renal_Cysts
  • 12/31/15, 4:40 PMPolycystic Kidney Disease, Autosomal Dominant - GeneReviews - NCBI Bookshelf

    Page 3 of 51http://www.ncbi.nlm.nih.gov/books/NBK1246/?report=printable

    1.

    without the presence of hepatic cysts and (2) absence of other manifestations suggestive of a different renal cysticdisease provide presumptive (though not definite) evidence for the diagnosis. Molecular testing may provide adefinitive diagnosis (see Testing Strategy).

    Renal Cysts

    Age-specific ultrasound criteria to confirm a diagnosis of ADPKD have been proposed for individuals who are at50% risk for ADPKD because they have an affected first-degree relative [Pei et al 2009].

    Note: The positive predictive value of these criteria is 100%, regardless of (1) which form of the disorder (PKD1 orPKD2) is present and (2) the age of the individual at the time of initial evaluation. However, the sensitivity of thecriteria depends on the underlying genotype and the age of the individual at the time of evaluation (see Table 1).

    Criteria:

    The presence of three or more (unilateral or bilateral) renal cysts in an individual age 15-39 years

    The presence of two or more cysts in each kidney in an individual age 40-59 years

    Large echogenic kidneys without distinct macroscopic cysts in an infant/child at 50% risk for ADPKD are diagnostic.

    Note: Although the ultrasound criteria listed above are appropriate to establish a diagnosis of ADPKD in anindividual at risk, their sensitivity is low (Table 1, 81.7%-95.5%), particularly in families who have a PKD2 or a mildPKD1 pathogenic variant (69.5%-94.9%). In this situation, a significant number of affected individuals may not bediagnosed, which may pose a problem when exclusion of the diagnosis is critical (see Testing Strategy,Presymptomatic diagnosis).

    Table 1.

    Ultrasound Criteria for Diagnosis of ADPKD in Individuals at 50% Risk for ADPKD Based on Family History

    Age PKD1 PKD2 Unknown ADPKD Genotype

    15-30 years3 cysts PPV = 100%SEN = 94.3%

    3 cysts PPV = 100%SEN = 69.5%

    3 cysts PPV = 100%SEN = 81.7%

    30-39 years3 cysts PPV = 100%SEN = 96.6%

    3 cysts PPV = 100%SEN = 94.9%

    3 cysts PPV = 100%SEN = 95.5%

    40-59 years2 cysts in each kidneyPPV = 100%SEN = 92.6%

    2 cysts in each kidneyPPV = 100%SEN = 88.8%

    2 cysts in each kidneyPPV = 100%SEN = 90%

    Derived from Pei et al [2009]. All values presented are mean estimates.

    PPV= positive predictive value

    SEN = sensitivity

    Unilateral or bilateral

    1 1 1

    1 1 1

    http://www.ncbi.nlm.nih.gov/books/NBK1246/?report=printable#pkd-ad.Testing_Strategyhttp://www.ncbi.nlm.nih.gov/books/NBK1246/?report=printable#http://www.ncbi.nlm.nih.gov/books/NBK1246/table/pkd-ad.T.ultrasound_criteria_for_diagnos/?report=objectonlyhttp://www.ncbi.nlm.nih.gov/books/NBK1246/table/pkd-ad.T.ultrasound_criteria_for_diagnos/?report=objectonlyhttp://www.ncbi.nlm.nih.gov/books/NBK124

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