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| __NOTOC__ | | __NOTOC__ |
| {{DiseaseDisorder infobox |
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| Name = Polycystic Kidney Disease |
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| ICD10 = {{ICD10|Q|61||q|60}} |
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| ICD9 = {{ICD9|753.1}} |
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| ICDO = |
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| Image = Polycystic kidneys, gross pathology 20G0027 lores.jpg |
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| Caption = Polycystic kidneys |
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| OMIM = 173900 |
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| MedlinePlus = 000502 |
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| DiseasesDB = 10262 |
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| DiseasesDB_mult= {{DiseasesDB2|10280}} |
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| MeshID = D007690 |
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| }}
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| {{Polycystic kidney disease}} | | {{Polycystic kidney disease}} |
| '''For patient information page, click [[{{PAGENAME}} (patient information)|here]] | | '''For patient information page, click [[{{PAGENAME}} (patient information)|here]]''' |
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| {{SCC}} | | {{CMG}}; {{AE}} {{MKA}}, [[User:Sergekorjian|Serge Korjian]], [[User:YazanDaaboul| Yazan Daaboul]] |
| '''Contributors:''' [[User:zorkun|Cafer Zorkun]] M.D., PhD.
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| {{SK}} Polycystic kidney syndrome; polycystic kidney; PKD | | {{SK}} Polycystic kidney syndrome; polycystic kidney; PKD; autosomal dominant polycystic kisney disease; ADPKD; autosomal recessive polycystic kidney disease; ARPKD |
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| ==Overview== | | ==[[Polycystic kidney disease overview|Overview]]== |
| '''Polycystic kidney disease''' is a progressive, [[genetic disorder]] of the [[kidney]]s. It occurs in [[human]]s and other [[organism]]s. PKD is characterized by the presence of multiple [[cyst]]s (hence, "polycystic") in both [[kidney]]s. The disease can also damage the [[liver]], [[pancreas]], and rarely, the [[heart]] and [[brain]]. The two major forms of polycystic kidney disease are distinguished by their patterns of inheritance.
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| [[Autosomal dominant]] polycystic kidney disease (ADPKD) is generally a late-onset disorder characterized by progressive cyst development and bilaterally enlarged kidneys with multiple cysts. Kidney manifestations in this disorder include renal function abnormalities, [[hypertension]], renal [[pain]], and [[renal insufficiency]]. Approximately 50% of patients with ADPKD have [[end stage renal disease]] ([[ESRD]]) by the age of 60. ADPKD is a systemic disease with cysts in other organs such as the [[liver]] (which may lead to [[cirrhosis]]), [[seminal vesicles]], pancreas, and [[arachnoid mater]] and non-cystic abnormalities such as intracranial [[aneurysms]] and [[dolichoectasias]], dilatation of the [[aortic]] root and dissection of the [[thoracic aorta]], [[mitral valve prolapse]], and abdominal wall hernias. | | ==[[Polycystic kidney disease historical perspective|Historical perspective]]== |
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| Initial simian and human [[symptom]]s are [[hypertension]], [[Fatigue (physical)|fatigue]], and mild to severe back or flank pain and [[urinary tract infection]]s. The disease often leads to [[chronic renal failure]] and may result in total loss of kidney function, known as [[end stage renal disease]] ([[ESRD]]), which requires some form of [[renal replacement therapy]] (e.g. [[dialysis]]).
| | ==[[Polycystic kidney disease classification|Classification]]== |
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| [[Autosomal recessive]] polycystic kidney disease (ARPKD) is much rarer than ADPKD and is often fatal in utero or during the first month of life. The signs and symptoms of the condition are usually apparent at birth or in early infancy. | | ==[[Polycystic kidney disease pathophysiology|Pathophysiology]]== |
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| ==Genetics == | | ==[[Polycystic kidney disease causes|Causes]]== |
| The disease exists both in an [[autosomal recessive]] and an [[autosomal dominant]] form.
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| ===Autosomal dominant form=== | | ==[[Polycystic kidney disease epidemiology and demographics|Epidemiology and Demographics]]== |
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| The autosomal dominant form, called ADPKD (autosomal dominant PKD or "Adult-onset PKD") is much more common but less severe. In 85% of patients, ADPKD is caused by [[mutation]]s in the [[gene]] ''[[PKD1]]'' on chromosome 16 (TRPP1); in 15% of patients mutations in ''[[PKD2]]'' (TRPP2) are causative. A third locus ''PKD3'' is the cause of a very small percentage of cases.
| | ==[[Polycystic kidney disease differentiating polycystic kidney disease from other diseases|Differentiating Polycystic kidney disease from Other Diseases]]== |
| * {{OMIM|173910}}, {{DiseasesDB|10262}}
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| [[Image:Autodominant.jpg|thumb|left|150px|ADPKD is inherited in an [[autosomal dominant]] pattern.]] | | ==[[Polycystic kidney disease risk factor|Risk Factors]]== |
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| ===Autosomal recessive form=== | | ==[[Polycystic kidney disease screening|Screening]]== |
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| The recessive form, called ARPKD (autosomal recessive polycystic kidney disease) is the less common variant. Mutations in the ''[[PKHD1]]'' (chromosomal locus 6p12.2) cause ARPKD.
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| * {{OMIM|263200}}, {{DiseasesDB|10280}}
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| [[Image:autorecessive.jpg|thumb|left|150px|ARPKD is inherited in an [[Recessive gene|autosomal recessive]] pattern.]] | | ==[[Polycystic kidney disease natural history|Natural History, Complications and Prognosis]]== |
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| ===Other types=== | | ==[[Polycystic kidney disease diagnosis|Diagnosis]]== |
| | [[Polycystic kidney disease diagnostic study of choice|Diagnostic Study of Choice]] | [[Polycystic kidney disease history and symptoms|History and Symptoms]] | [[Polycystic kidney disease physical examination|Physical Examination]] | [[Polycystic kidney disease laboratory findings|Laboratory Findings]] | [[Polycystic kidney disease electrocardiogram|Electrocardiogram]] | [[Polycystic kidney disease CT|CT]] | [[Polycystic kidney disease MRI|MRI]] | [[Polycystic kidney disease ultrasound|Ultrasound]] | [[Polycystic kidney disease other imaging findings|Other Imaging Findings]] | [[Polycystic kidney disease other diagnostic studies|Other Diagnostic Studies]] |
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| A small number of families with polycystic kidney disease do not have apparent mutations in any of the three known genes. An unidentified gene or genes may also be responsible for this disease. In this case, the disease is designated "PKD3".
| | ==[[Polycystic kidney disease treatment|Treatment]]== |
| | :[[Polycystic kidney disease medical therapy|Medical Therapy]] | [[Polycystic kidney disease surgery|Surgery]] | [[Polycystic kidney disease primary prevention|Primary Prevention]] | [[Polycystic kidney disease secondary prevention|Secondary Prevention]] | [[Polycystic kidney disease future or investigational therapies|Future or Investigational Therapies]] |
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| ==Epidemiology== | | ==Case Studies== |
| | | [[Polycystic kidney disease case study one|Case #1]] |
| Polycystic kidney disease is the most common life-threatening genetic disease, affecting approximately 7 million people worldwide. Autosomal dominant polycystic kidney disease affects up to 1 in 1000 people, while the autosomal recessive type is estimated to occur in approximately 1 in 20,000 people.<ref name="Dalgaard_1957">{{cite journal |author=DALGAARD OZ |title=Bilateral polycystic disease of the kidneys; a follow-up of two hundred and eighty-four patients and their families |journal=Acta Med. Scand. Suppl. |volume=328 |issue= |pages=1-255 |year=1957 |pmid=13469269 |doi=}}</ref><ref name="Zerres_1998">{{cite journal |author=Zerres K, Mücher G, Becker J, ''et al'' |title=Prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD): molecular genetics, clinical experience, and fetal morphology |journal=Am. J. Med. Genet. |volume=76 |issue=2 |pages=137-44 |year=1998 |pmid=9511976 |doi=}}</ref>
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| ==Pathophysiology==
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| Recent studies in fundamental cell biology of [[cilia]]/[[flagella]] using experimental [[model organisms]] like the green algae ''[[Chlamydomonas]]'', the round worm ''[[Caenorhabditis elegans]]'' and the mouse ''[[Mus musculus]]'' have shed light on how PKD develops in patients. All [[cilia]] and [[flagella]] are constructed and maintained, including localizing of proteins inserted into ciliary and flagellar membranes, by the process of [[intraflagellar transport]]. Environmental sensing and cellular signaling pathways initiated from proteins inserted into ciliary/flagellar membranes are thought to be critical for normal renal cell development and functioning. Membrane proteins which function in developmental and physiological environmental sensing and intracellular signalling are sorted to and localized to the cilia in renal epithelial cells by [[intraflagellar transport]]. These epithelial cells line the lumen of the urinary collecting ducts and sense the flow of urine. Failure in flow-sensing signaling results in programmed cell death or [[apoptosis]] of these renal epithelial cells producing the characteristic multiple cysts of PKD. PKD may result from mutations of signaling and environmental sensing proteins, or failure in [[intraflagellar transport]]. Two PKD genes, ''PKD1'' and ''PKD2'', encode membrane proteins which localize to a non-motile cilium on the renal tube cell. Polycystin-2 encoded by ''PKD2'' gene is a calcium channel which allows extracellular calcium ions to enter the cell. Polycystin-1, encoded by ''PKD1'' gene, is thought to be associated with polycystin-2 protein and regulate its channel activity. The calcium ions are important cellular messengers which, in turn, trigger complicated biochemical pathways which lead to quiescence and differentiation. Malfunctions of polycystin-1 or polycystin-2 proteins, defects in the assembly of the cilium on the renal tube cell, failures in targeting these two proteins to the cilium, and deregulations of calcium signaling all likely cause the occurrence of PKD.
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| '''PKD and the "two hit" hypothesis:'''
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| The two hit hypothesis (aka [[Knudson hypothesis]] ) is often used to explain the manifestation of polycystic kidney disease later in life even though the mutation is present at birth. This term is borrowed from cancer research stating that both copies of the gene present in the genome have to be "silenced" before cancer manifests itself (in Knudson's case the silenced gene was ''Rb1''). In ADPKD the original "hit" is congenital (in either the ''PKD1'' or ''PKD2'' genes) and the subsequent "hit" occurs later in life as the cells grow and divide. The two hit hypothesis as it relates to PKD was originally proposed by Reeders in 1992.<ref>{{cite journal |author=Reeders ST |title=Multilocus polycystic disease |journal=Nat. Genet. |volume=1 |issue=4 |pages=235-7 |year=1992 |pmid=1338768 |doi=10.1038/ng0792-235}}</ref> Support for this hypothesis comes from the fact that ARPKD patients develop disease at birth, and [[Mutation|somatic mutations]] in the "normal" copy of ''PKD1'' or ''PKD2'' have been found in cyst-lining [[epithelia]]
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| ==Diagnosis==
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| A definite diagnosis of ADPKD relies on imaging or molecular [[genetic testing]]. The sensitivity of testing is nearly 100% for all patients with ADPKD who are age 30 years or older and for younger patients with PKD1 mutations; these criteria are only 67% sensitive for patients with PKD2 mutations who are younger than age 30 years. Large [[echogenic]] kidneys without distinct macroscopic cysts in an infant/child at 50% risk for ADPKD are diagnostic. In the absence of a family history of ADPKD, the presence of bilateral renal enlargement and cysts, with or without the presence of [[hepatic]] cysts, and the absence of other manifestations suggestive of a different renal cystic disease provide presumptive, but not definite, evidence for the diagnosis.
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| Molecular [[genetic testing]] by [[linkage analysis]] or direct mutation screening is available clinically; however, genetic heterogeneity is a significant complication to molecular genetic testing. Sometimes a relatively large number of affected family members need to be tested in order to establish which one of the two possible genes is responsible within each family. The large size and complexity of PKD1 and PKD2 [[gene]]s, as well as marked allelic heterogeneity, present obstacles to molecular testing by direct DNA analysis. In the research setting, [[mutation]] detection rates of 50-75% have been obtained for PKD1 and ~75% for PKD2. Clinical testing of the PKD1 and PKD2 genes by direct [[sequence analysis]] is now available, with a detection rate for disease-causing mutations of 50-70%.
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| [[Genetic counseling]] may be helpful for families at risk for polycystic kidney disease.
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| ==Diagnostic Findings==
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| ===Autosomal recessive form===
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| ====USG====
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| * At USG, the kidneys are massively enlarged and diffusely echogenic bilaterally.
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| * Corticomedullary differentiation is absent.
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| * High-resolution USG (linear-array transducer, 7.5 mHz or greater) allows visualization of numerous cylindrical cysts in the medulla and cortex, which represent ectatic collecting ducts.
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| [http://www.radswiki.net Images courtesy of RadsWiki]
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| [[Image:Autosomal-recessive-polycystic-kidney-disease-001.jpg|thumb|left|350px|MRI demonstrates typical imaging features of autosomal recessive polycystic kidney disease]]
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| <br clear="left"/>
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| [[Image:Autosomal-recessive-polycystic-kidney-disease-002.jpg|thumb|left|350px|MRI demonstrates typical imaging features of autosomal recessive polycystic kidney disease]]
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| <br clear="left"/>
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| [[Image:Autosomal-recessive-polycystic-kidney-disease-003.jpg|thumb|left|350px|MRI demonstrates typical imaging features of autosomal recessive polycystic kidney disease]]
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| ===Autosomal dominant form===
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| * Multiple, variably sized cortical and medullary based cysts
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| * Renomegaly
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| * Hemorrhagic cysts are often present
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| [http://www.radswiki.net Images courtesy of RadsWiki]
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| '''Patient #1'''
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| [[Image:Autosomal Dominant-polycystic-kidney-disease-001.jpg|thumb|left|350px|Autosomal dominant form of polycystic kidney disease
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| ]]
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| [[Image:Autosomal Dominant-polycystic-kidney-disease-002.jpg|thumb|left|350px|Autosomal dominant form of polycystic kidney disease
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| ]]
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| [[Image:Autosomal Dominant-polycystic-kidney-disease-003.jpg|thumb|left|350px|Autosomal dominant form of polycystic kidney disease
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| ]]
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| [[Image:Autosomal Dominant-polycystic-kidney-disease-004.jpg|thumb|left|350px|Autosomal dominant form of polycystic kidney disease
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| ]]
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| [[Image:Autosomal Dominant-polycystic-kidney-disease-005.jpg|thumb|left|350px|Autosomal dominant form of polycystic kidney disease
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| '''Patient #2'''
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| [[Image:Polycystic-kidneys-001.jpg|thumb|left|350px|Autosomal dominant form of polycystic kidney disease]]
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| [[Image:Polycystic-kidneys-002.jpg|thumb|left|350px|Autosomal dominant form of polycystic kidney disease]]
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| [[Image:Polycystic-kidneys-003.jpg|thumb|left|350px|Autosomal dominant form of polycystic kidney disease]]
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| '''Patient #3'''
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| [[Image:Autosomal dominant polycystic kidney disease 101.jpg|thumb|left|350px|Autosomal dominant form of polycystic kidney disease
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| [[Image:Autosomal dominant polycystic kidney disease 102.jpg|thumb|left|350px|Autosomal dominant form of polycystic kidney disease
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| '''Patient #4'''
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| [[Image:adpkd3011163.jpg|thumb|left|350px|Autosomal dominant form of polycystic kidney disease]]
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| ==Treatment==
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| Although a cure for PKD is not available, treatment can ease the symptoms and prolong life.
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| * [[Pain]]: Over-the-counter pain medications, such as [[paracetamol]] can relieve pain. For most but not all cases of severe pain, surgery to shrink cysts can relieve pain in the back and flanks. However, surgery provides only temporary relief and usually does not slow the disease's progression toward [[kidney failure]].
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| * [[Urinary tract infection]]s: Patients with PKD tend to have frequent urinary tract infections, which can be treated with [[antibiotic]]s. Early treatment is important, because infection can spread from the urinary tract to the cysts in the kidneys. Cyst infections are difficult to treat because many antibiotics do not penetrate into the cysts. However, some antibiotics are effective.
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| * [[High blood pressure]]: Keeping blood pressure under control can slow the effects of PKD. Lifestyle changes and various medications can lower high blood pressure.
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| * [[End-stage renal disease]]: There are two options for replacing kidney functions: [[dialysis]] or [[Kidney_transplant|transplantation]]. Healthy (non-PKD) kidneys transplanted into PKD patients do not develop cysts.
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| ==Pathological Findings==
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| [http://www.peir.net Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
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| [[Image:Infantile polycystic disease.jpg|thumb|left|350px|Infantile polycystic disease: Gross natural color view of both kidneys with ureters and uterus (very good example) ]]
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| ===Adult type Polycystic kidney disease===
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| <youtube v=6Ws9cfsjZIk/>
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| ==Resources==
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| The [http://www.pkdcure.org PKD Foundation] is the only non-profit organization worldwide dedicated solely to PKD research.
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| Parent of two children with ARPKD blog: www.kidneysandeyes.com
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| ==References==
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| <references/>
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| * {{cite journal |author=Nauli SM, Zhou J |title=Polycystins and mechanosensation in renal and nodal cilia |journal=Bioessays |volume=26 |issue=8 |pages=844-56 |year=2004 |pmid=15273987 |doi=10.1002/bies.20069}}
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| * {{cite journal |author=Grantham JJ, Torres VE, Chapman AB, ''et al'' |title=Volume progression in polycystic kidney disease |journal=N. Engl. J. Med. |volume=354 |issue=20 |pages=2122-30 |year=2006 |pmid=16707749 |doi=10.1056/NEJMoa054341}}
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| ==External links== | | ==External links== |
| *http://www.ncbi.nlm.nih.gov/disease/PKD.html | | *http://www.ncbi.nlm.nih.gov/disease/PKD.html |
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| {{SIB}}
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| {{Congenital malformations of genital organs and urinary system}} | | {{Congenital malformations of genital organs and urinary system}} |
| {{Cystic diseases}} | | {{Cystic diseases}} |
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| [[Category:Urology]] | | [[Category:Urology]] |
| [[Category:Channelopathy]] | | [[Category:Channelopathy]] |
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| [[de:Zystenniere]] | |
| [[es:Enfermedad poliquística renal]]
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| [[fr:Polykystose rénale type dominant]]
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| [[nl:Polycysteuze nieren]]
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| [[ja:常染色体性優性多発性嚢胞腎]]
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| [[pt:Doença do rim policístico]]
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| [[sv:Polycystisk njursjukdom]]
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| [[zh:多囊性腎病變]]
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| {{WH}} | | {{WH}} |
| {{WS}} | | {{WS}} |