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Polycystic kidney disease 2(PKD2)

MedGen UID:
442699
Concept ID:
C2751306
Disease or Syndrome
Synonyms: PKD2; POLYCYSTIC KIDNEY DISEASE 2 WITH OR WITHOUT POLYCYSTIC LIVER DISEASE; Polycystic Kidney Disease 2, Autosomal Dominant; POLYCYSTIC KIDNEY DISEASE, ADULT, TYPE II
SNOMED CT: Adult type polycystic kidney disease type 2 (253879006); PKD2 - Polycystic kidney disease 2 (253879006); Autosomal dominant polycystic kidney disease type 2 (253879006)
 
Gene (location): PKD2 (4q22.1)
 
Monarch Initiative: MONDO:0013131
OMIM®: 613095

Disease characteristics

Excerpted from the GeneReview: Polycystic Kidney Disease, Autosomal Dominant
Autosomal dominant polycystic kidney disease (ADPKD) is generally a late-onset multisystem disorder characterized by bilateral kidney cysts, liver cysts, and an increased risk of intracranial aneurysms. Other manifestations include: cysts in the pancreas, seminal vesicles, and arachnoid membrane; dilatation of the aortic root and dissection of the thoracic aorta; mitral valve prolapse; and abdominal wall hernias. Kidney manifestations include early-onset hypertension, kidney pain, and kidney insufficiency. Approximately 50% of individuals with ADPKD have end-stage kidney disease (ESKD) by age 60 years. The prevalence of liver cysts increases with age and occasionally results in clinically significant severe polycystic liver disease (PLD), most often in females. Overall, the prevalence of intracranial aneurysms is fivefold higher than in the general population and further increased in those with a positive family history of aneurysms or subarachnoid hemorrhage. There is substantial variability in the severity of kidney disease and other extra-kidney manifestations. [from GeneReviews]
Authors:
Peter C Harris  |  Vicente E Torres   view full author information

Additional description

From MedlinePlus Genetics
Polycystic kidney disease is a disorder that affects the kidneys and other organs. Clusters of fluid-filled sacs, called cysts, develop in the kidneys and interfere with their ability to filter waste products from the blood. The growth of cysts causes the kidneys to become enlarged and can lead to kidney failure. Cysts may also develop in other organs, particularly the liver.

Frequent complications of polycystic kidney disease include dangerously high blood pressure (hypertension), pain in the back or sides, blood in the urine (hematuria), recurrent urinary tract infections, kidney stones, and heart valve abnormalities. Additionally, people with polycystic kidney disease have an increased risk of an abnormal bulging (an aneurysm) in a large blood vessel called the aorta or in blood vessels at the base of the brain. Aneurysms can be life-threatening if they tear or rupture.

The two major forms of polycystic kidney disease are distinguished by the usual age of onset and the pattern in which it is passed through families. The autosomal dominant form (sometimes called ADPKD) has signs and symptoms that typically begin in adulthood, although cysts in the kidney are often present from birth or childhood. Autosomal dominant polycystic kidney disease can be further divided into type 1 and type 2, depending on the genetic cause. The autosomal recessive form of polycystic kidney disease (sometimes called ARPKD) is much rarer and is often lethal early in life. The signs and symptoms of this condition are usually apparent at birth or in early infancy.  https://medlineplus.gov/genetics/condition/polycystic-kidney-disease

Clinical features

From HPO
Polycystic kidney disease
MedGen UID:
9639
Concept ID:
C0022680
Disease or Syndrome
The presence of multiple cysts in both kidneys.
Recurrent urinary tract infections
MedGen UID:
120466
Concept ID:
C0262655
Disease or Syndrome
Repeated infections of the urinary tract.
Multiple renal cysts
MedGen UID:
140917
Concept ID:
C0431718
Disease or Syndrome
The presence of many cysts in the kidney.
Renal insufficiency
MedGen UID:
332529
Concept ID:
C1565489
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Dextrocardia
MedGen UID:
4255
Concept ID:
C0011813
Congenital Abnormality
The heart is located in the right hand sided hemithorax. That is, there is a left-right reversal (or "mirror reflection") of the anatomical location of the heart in which the heart is locate on the right side instead of the left.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Situs inversus
MedGen UID:
1642262
Concept ID:
C4551493
Congenital Abnormality
A left-right reversal (or mirror reflection) of the anatomical location of the major thoracic and abdominal organs.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Hepatic cysts
MedGen UID:
82761
Concept ID:
C0267834
Disease or Syndrome
A cystic lesion located in the liver.
Hypokalemia
MedGen UID:
5712
Concept ID:
C0020621
Finding
An abnormally decreased potassium concentration in the blood.
Elevated circulating alpha-fetoprotein concentration
MedGen UID:
65916
Concept ID:
C0235971
Finding
Concentration of alpha-fetoprotein in the blood circulation above the upper limit of normal.
Elevated circulating creatinine concentration
MedGen UID:
148579
Concept ID:
C0700225
Finding
An increased amount of creatinine in the blood.
Elevated circulating alkaline phosphatase concentration
MedGen UID:
727252
Concept ID:
C1314665
Finding
Abnormally increased serum levels of alkaline phosphatase activity.
Elevated gamma-glutamyltransferase level
MedGen UID:
1370086
Concept ID:
C4476869
Finding
Increased level of the enzyme gamma-glutamyltransferase (GGT). GGT is mainly present in kidney, liver, and pancreatic cells, but small amounts are present in other tissues.
Facial asymmetry
MedGen UID:
266298
Concept ID:
C1306710
Finding
An abnormal difference between the left and right sides of the face.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.

Professional guidelines

PubMed

Mizoguchi M, Tamura T, Yamaki A, Higashihara E, Shimizu Y
J Hum Genet 2002;47(1):51-4. doi: 10.1007/s10038-002-8654-5. PMID: 11829141
Kim EK, Song TB
J Obstet Gynaecol Res 1996 Dec;22(6):569-73. doi: 10.1111/j.1447-0756.1996.tb01072.x. PMID: 9037946

Recent clinical studies

Etiology

McConnachie DJ, Stow JL, Mallett AJ
Am J Kidney Dis 2021 Mar;77(3):410-419. Epub 2020 Oct 9 doi: 10.1053/j.ajkd.2020.08.012. PMID: 33039432
Kim H, Park HC, Ryu H, Kim H, Lee HS, Heo J, Lee C, Kim NKD, Park WY, Hwang YH, Lee KB, Oh KH, Oh YK, Ahn C
Sci Rep 2019 Nov 18;9(1):16952. doi: 10.1038/s41598-019-52474-1. PMID: 31740684Free PMC Article
Cornec-Le Gall E, Torres VE, Harris PC
J Am Soc Nephrol 2018 Jan;29(1):13-23. Epub 2017 Oct 16 doi: 10.1681/ASN.2017050483. PMID: 29038287Free PMC Article
Carrera P, Calzavara S, Magistroni R, den Dunnen JT, Rigo F, Stenirri S, Testa F, Messa P, Cerutti R, Scolari F, Izzi C, Edefonti A, Negrisolo S, Benetti E, Alibrandi MT, Manunta P, Boletta A, Ferrari M
Sci Rep 2016 Aug 8;6:30850. doi: 10.1038/srep30850. PMID: 27499327Free PMC Article
Cornec-Le Gall E, Audrézet MP, Chen JM, Hourmant M, Morin MP, Perrichot R, Charasse C, Whebe B, Renaudineau E, Jousset P, Guillodo MP, Grall-Jezequel A, Saliou P, Férec C, Le Meur Y
J Am Soc Nephrol 2013 May;24(6):1006-13. Epub 2013 Feb 21 doi: 10.1681/ASN.2012070650. PMID: 23431072Free PMC Article

Diagnosis

Mallawaarachchi AC, Lundie B, Hort Y, Schonrock N, Senum SR, Gayevskiy V, Minoche AE, Hollway G, Ohnesorg T, Hinchcliffe M, Patel C, Tchan M, Mallett A, Dinger ME, Rangan G, Cowley MJ, Harris PC, Burnett L, Shine J, Furlong TJ
Eur J Hum Genet 2021 May;29(5):760-770. Epub 2021 Jan 12 doi: 10.1038/s41431-020-00796-4. PMID: 33437033Free PMC Article
Kim H, Park HC, Ryu H, Kim H, Lee HS, Heo J, Lee C, Kim NKD, Park WY, Hwang YH, Lee KB, Oh KH, Oh YK, Ahn C
Sci Rep 2019 Nov 18;9(1):16952. doi: 10.1038/s41598-019-52474-1. PMID: 31740684Free PMC Article
Cornec-Le Gall E, Torres VE, Harris PC
J Am Soc Nephrol 2018 Jan;29(1):13-23. Epub 2017 Oct 16 doi: 10.1681/ASN.2017050483. PMID: 29038287Free PMC Article
Audrézet MP, Cornec-Le Gall E, Chen JM, Redon S, Quéré I, Creff J, Bénech C, Maestri S, Le Meur Y, Férec C
Hum Mutat 2012 Aug;33(8):1239-50. Epub 2012 May 24 doi: 10.1002/humu.22103. PMID: 22508176
Pei Y, Obaji J, Dupuis A, Paterson AD, Magistroni R, Dicks E, Parfrey P, Cramer B, Coto E, Torra R, San Millan JL, Gibson R, Breuning M, Peters D, Ravine D
J Am Soc Nephrol 2009 Jan;20(1):205-12. Epub 2008 Oct 22 doi: 10.1681/ASN.2008050507. PMID: 18945943Free PMC Article

Therapy

Xu Y, Li A, Wu G, Liang C
Curr Gene Ther 2017;17(1):43-49. doi: 10.2174/1566523217666170510152808. PMID: 28494735
Rangan GK, Tchan MC, Tong A, Wong AT, Nankivell BJ
Intern Med J 2016 Aug;46(8):883-92. doi: 10.1111/imj.13143. PMID: 27553994
Chang MY, Ong AC
Br J Clin Pharmacol 2013 Oct;76(4):524-35. doi: 10.1111/bcp.12136. PMID: 23594398Free PMC Article
Czarnecki PG, Steinman TI
Minerva Urol Nefrol 2013 Mar;65(1):61-8. PMID: 23538311
Sun Y, Zhou H, Yang BX
Acta Pharmacol Sin 2011 Jun;32(6):805-16. doi: 10.1038/aps.2011.29. PMID: 21642949Free PMC Article

Prognosis

Mallawaarachchi AC, Lundie B, Hort Y, Schonrock N, Senum SR, Gayevskiy V, Minoche AE, Hollway G, Ohnesorg T, Hinchcliffe M, Patel C, Tchan M, Mallett A, Dinger ME, Rangan G, Cowley MJ, Harris PC, Burnett L, Shine J, Furlong TJ
Eur J Hum Genet 2021 May;29(5):760-770. Epub 2021 Jan 12 doi: 10.1038/s41431-020-00796-4. PMID: 33437033Free PMC Article
Kim H, Park HC, Ryu H, Kim H, Lee HS, Heo J, Lee C, Kim NKD, Park WY, Hwang YH, Lee KB, Oh KH, Oh YK, Ahn C
Sci Rep 2019 Nov 18;9(1):16952. doi: 10.1038/s41598-019-52474-1. PMID: 31740684Free PMC Article
Cornec-Le Gall E, Torres VE, Harris PC
J Am Soc Nephrol 2018 Jan;29(1):13-23. Epub 2017 Oct 16 doi: 10.1681/ASN.2017050483. PMID: 29038287Free PMC Article
Cornec-Le Gall E, Audrézet MP, Chen JM, Hourmant M, Morin MP, Perrichot R, Charasse C, Whebe B, Renaudineau E, Jousset P, Guillodo MP, Grall-Jezequel A, Saliou P, Férec C, Le Meur Y
J Am Soc Nephrol 2013 May;24(6):1006-13. Epub 2013 Feb 21 doi: 10.1681/ASN.2012070650. PMID: 23431072Free PMC Article
Wilson PD
N Engl J Med 2004 Jan 8;350(2):151-64. doi: 10.1056/NEJMra022161. PMID: 14711914

Clinical prediction guides

Mallawaarachchi AC, Lundie B, Hort Y, Schonrock N, Senum SR, Gayevskiy V, Minoche AE, Hollway G, Ohnesorg T, Hinchcliffe M, Patel C, Tchan M, Mallett A, Dinger ME, Rangan G, Cowley MJ, Harris PC, Burnett L, Shine J, Furlong TJ
Eur J Hum Genet 2021 May;29(5):760-770. Epub 2021 Jan 12 doi: 10.1038/s41431-020-00796-4. PMID: 33437033Free PMC Article
Cornec-Le Gall E, Audrézet MP, Rousseau A, Hourmant M, Renaudineau E, Charasse C, Morin MP, Moal MC, Dantal J, Wehbe B, Perrichot R, Frouget T, Vigneau C, Potier J, Jousset P, Guillodo MP, Siohan P, Terki N, Sawadogo T, Legrand D, Menoyo-Calonge V, Benarbia S, Besnier D, Longuet H, Férec C, Le Meur Y
J Am Soc Nephrol 2016 Mar;27(3):942-51. Epub 2015 Jul 6 doi: 10.1681/ASN.2015010016. PMID: 26150605Free PMC Article
Saigusa T, Bell PD
Physiology (Bethesda) 2015 May;30(3):195-207. doi: 10.1152/physiol.00032.2014. PMID: 25933820Free PMC Article
Cornec-Le Gall E, Audrézet MP, Chen JM, Hourmant M, Morin MP, Perrichot R, Charasse C, Whebe B, Renaudineau E, Jousset P, Guillodo MP, Grall-Jezequel A, Saliou P, Férec C, Le Meur Y
J Am Soc Nephrol 2013 May;24(6):1006-13. Epub 2013 Feb 21 doi: 10.1681/ASN.2012070650. PMID: 23431072Free PMC Article
Witzgall R
Handb Exp Pharmacol 2007;(179):363-75. doi: 10.1007/978-3-540-34891-7_22. PMID: 17217069

Recent systematic reviews

Schrier RW, Brosnahan G, Cadnapaphornchai MA, Chonchol M, Friend K, Gitomer B, Rossetti S
J Am Soc Nephrol 2014 Nov;25(11):2399-418. Epub 2014 Jun 12 doi: 10.1681/ASN.2013111184. PMID: 24925719Free PMC Article

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