Title: Autosomal dominant polycystic kidney disease

{{Infobox medical condition (new)
| name            = Autosomal dominant polycystic kidney disease
| synonyms        = Autosomal dominant PKD, adult-onset PKD
| image           = Polycystic kidneys, gross pathology CDC PHIL.png
| caption         = Polycystic kidneys
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[[File:Polycystic kidney.jpg|thumb|polycystic kidney, external surface with multiple cysts.]]
[[File:Kiney with multiple cysts, some with old and more recent haemorrhage.jpg|thumb|Cut surface of kidney showing multiple cysts with old and more recent haemorrhage.]]
'''Autosomal dominant polycystic kidney disease''' ('''ADPKD''') is one of the most common, life-threatening [[Genetic disorder|inherited human disorders]] and the most common hereditary [[kidney disease]].&lt;ref name=&quot;TP-150518-E20&quot;&gt;{{cite journal | vauthors = Torres VE, Harris PC, Pirson Y | title = Autosomal dominant polycystic kidney disease | journal = Lancet | volume = 369 | issue = 9569 | pages = 1287–1301 | date = April 2007 | pmid = 17434405 | doi = 10.1016/S0140-6736(07)60601-1 | s2cid = 1700992 }}&lt;/ref&gt;&lt;ref&gt;{{Cite web |title=What is ADPKD? |url=https://pkdcure.org/what-is-adpkd/ |access-date=2022-09-23 |website=PKD Foundation |language=en-US}}&lt;/ref&gt; It is associated with large interfamilial and intrafamilial variability, which can be explained to a large extent by its genetic heterogeneity and [[modifier gene]]s.&lt;ref name=&quot;TP-150518-E20&quot; /&gt; It is also the most common of the inherited [[cystic kidney disease]]s — a group of disorders with related but distinct pathogenesis, characterized by the development of [[renal cyst]]s and various extrarenal manifestations, which in case of ADPKD include cysts in other organs, such as the [[liver]], [[seminal vesicle]]s, [[pancreas]], and [[arachnoid membrane]], as well as other abnormalities, such as intracranial [[aneurysm]]s and [[Intracranial dolichoectasias|dolichoectasias]], [[aortic root]] dilatation and aneurysms, [[mitral valve]] prolapse, and [[abdominal wall]] [[hernia]]s.&lt;ref name=&quot;TP-150518-E20&quot; /&gt;&lt;ref name=&quot;Dalgaard_1957&quot;&gt;{{cite journal | vauthors = Dalgaard OZ | title = Bilateral polycystic disease of the kidneys; a follow-up of two hundred and eighty-four patients and their families | journal = Acta Medica Scandinavica. Supplementum | volume = 328 | pages = 1–255 | year = 1957 | pmid = 13469269 }}&lt;/ref&gt;&lt;ref name=torres&gt;{{cite journal | vauthors = Torres VE, Harris PC | title = Autosomal dominant polycystic kidney disease: the last 3 years | journal = Kidney International | volume = 76 | issue = 2 | pages = 149–168 | date = July 2009 | pmid = 19455193 | pmc = 2812475 | doi = 10.1038/ki.2009.128 }}&lt;/ref&gt; Over 50% of patients with ADPKD eventually develop [[Kidney failure|end stage kidney disease]] and require [[Kidney dialysis|dialysis]] or [[kidney transplantation]].&lt;ref name=&quot;TP-150518-E20&quot; /&gt;&lt;ref name=&quot;grantham&quot;&gt;{{cite journal | vauthors = Grantham JJ | title = Clinical practice. Autosomal dominant polycystic kidney disease | journal = The New England Journal of Medicine | volume = 359 | issue = 14 | pages = 1477–1485 | date = October 2008 | pmid = 18832246 | doi = 10.1056/NEJMcp0804458 | pmc = 2843931 }}; Reprinted in {{cite journal | vauthors = Niemczyk M, Niemczyk S, Paczek L | title = Autosomal dominant polycystic kidney disease and transplantation | journal = Annals of Transplantation | volume = 14 | issue = 4 | pages = 86–90 | year = 2009 | pmid = 20009161 | pmc = 2843931 }}&lt;/ref&gt; ADPKD is estimated to affect at least one in every 1000 individuals worldwide, making this disease the most common inherited kidney disorder with a diagnosed prevalence of 1:2000 and incidence of 1:3000-1:8000 in a global scale.&lt;ref name=&quot;TP-150514-001&quot;&gt;{{cite journal | vauthors = Muto S, Kawano H, Higashihara E, Narita I, Ubara Y, Matsuzaki T, Ouyang J, Torres VE, Horie S | display-authors = 6 | title = The effect of tolvaptan on autosomal dominant polycystic kidney disease patients: a subgroup analysis of the Japanese patient subset from TEMPO 3:4 trial | journal = Clinical and Experimental Nephrology | volume = 19 | issue = 5 | pages = 867–877 | date = October 2015 | pmid = 25663351 | doi = 10.1007/s10157-015-1086-2 | s2cid = 12124902 }}&lt;/ref&gt;&lt;ref name=&quot;TP-150518-E18&quot;&gt;{{cite journal | vauthors = Higashihara E, Nutahara K, Kojima M, Tamakoshi A, Yoshiyuki O, Sakai H, Kurokawa K | title = Prevalence and renal prognosis of diagnosed autosomal dominant polycystic kidney disease in Japan | journal = Nephron | volume = 80 | issue = 4 | pages = 421–427 | date = December 1998 | pmid = 9832641 | doi = 10.1159/000045214 | s2cid = 22124996 }}&lt;/ref&gt;&lt;ref name=&quot;TP-150514-003&quot;&gt;{{cite journal | vauthors = Levy M, Feingold J | title = Estimating prevalence in single-gene kidney diseases progressing to renal failure | journal = Kidney International | volume = 58 | issue = 3 | pages = 925–943 | date = September 2000 | pmid = 10972657 | doi = 10.1046/j.1523-1755.2000.00250.x | doi-access = free }}&lt;/ref&gt;&lt;ref name=&quot;TP-150514-004&quot;&gt;{{cite journal | vauthors = Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS | display-authors = 6 | title = Tolvaptan in patients with autosomal dominant polycystic kidney disease | journal = The New England Journal of Medicine | volume = 367 | issue = 25 | pages = 2407–2418 | date = December 2012 | pmid = 23121377 | pmc = 3760207 | doi = 10.1056/NEJMoa1205511 }}&lt;/ref&gt;&lt;ref name=&quot;TP-150514-005&quot;&gt;{{cite journal | vauthors = Cornec-Le Gall E, Le Meur Y | title = [Autosomal dominant polycystic kidney disease: is the treatment for tomorrow?] | journal = Nephrologie &amp; Therapeutique | volume = 10 | issue = 6 | pages = 433–440 | date = November 2014 | pmid = 25086476 | doi = 10.1016/j.nephro.2014.03.003 }}&lt;/ref&gt;

==Signs and symptoms==
ADPKD can result in a wide variety of clinical symptoms. Symptoms may be caused directly by a cyst growing or bursting, or indirectly due to problems with other physiological functions. Most symptoms occur around 40 years of age, but some clinical symptoms can occur decades prior to the development of over kidney disease, with some symptoms presenting as early as childhood.&lt;ref name=&quot;:0&quot;&gt;{{Cite journal |last1=Bergmann |first1=Carsten |last2=Guay-Woodford |first2=Lisa M. |last3=Harris |first3=Peter C. |last4=Horie |first4=Shigeo |last5=Peters |first5=Dorien J. M. |last6=Torres |first6=Vicente E. |date=2018-12-06 |title=Polycystic kidney disease |journal=Nature Reviews Disease Primers |language=en |volume=4 |issue=1 |article-number=50 |doi=10.1038/s41572-018-0047-y |issn=2056-676X |pmc=6592047 |pmid=30523303}}&lt;/ref&gt;&lt;ref name=&quot;:1&quot;&gt;{{Cite journal |last1=Perumareddi |first1=Parvathi |last2=Trelka |first2=Darin P. |date=December 2020 |title=Autosomal Dominant Polycystic Kidney Disease |url=https://linkinghub.elsevier.com/retrieve/pii/S0095454320300646 |journal=Primary Care: Clinics in Office Practice |language=en |volume=47 |issue=4 |pages=673–689 |doi=10.1016/j.pop.2020.08.010|url-access=subscription }}&lt;/ref&gt;

Primary Symptoms Include:&lt;ref name=&quot;:1&quot; /&gt;

* Early-onset hypertension
* Blood in urine
* Abdominal, flank, or back pain
* Masses in the abdomen or flank
* Decrease in renal function

Among the most common symptoms associated with it is early-onset hypertension. Early-onset hypertension is present in 50%-70% of individuals with ADPKD.&lt;ref name=&quot;:0&quot; /&gt; Hypertension can even develop before the decline in kidney function markers like GFR (glomerular filtration rate).&lt;ref name=&quot;:0&quot; /&gt;

The presence of ADPKD is associated with several extra-renal symptoms, including the development of cysts in organs outside of the kidney. Polycystic liver disease is often found in adults with ADPKD and can be present in greater than 90% of individuals with ADPKD over 35 years old.&lt;ref name=&quot;:2&quot;&gt;{{Cite journal |last1=Gall |first1=Emilie Cornec-Le |last2=Alam |first2=Ahsan |last3=Perrone |first3=Ronald D. |date=2019-03-02 |title=Autosomal dominant polycystic kidney disease |url=https://linkinghub.elsevier.com/retrieve/pii/S014067361832782X |journal=The Lancet |language=English |volume=393 |issue=10174 |pages=919–935 |doi=10.1016/S0140-6736(18)32782-X |issn=0140-6736 |pmid=30819518|url-access=subscription }}&lt;/ref&gt; Polycystic liver disease develops more often in females with ADPKD than males, with risk factors including and exposure to non-endogenous sources of estrogen and multiple gestations. Individuals with polycystic liver disease due to ADPKD can also experience gastrointestinal symptoms related to the presence of cysts in the liver, such as early discomfort, fullness, and gastroesophageal reflux. In rare cases, portal hypertension with secondary ascites and pleural effusion can also occur.

Individuals with ADPKD are also at increased risk for developing intracranial aneurysms. The risk of intracranial aneurysms is estimated to be four times higher in people with ADPKD when compared to the general population, and as a result, screening with magnetic resonance angiography is recommended for high-risk populations.&lt;ref name=&quot;:2&quot; /&gt;

Additionally, symptoms such as abdominal fullness, excessive urination, and recurring urinary tract infections (occurring more frequently in women than in men), kidney stones, and bladder infection are also associated with ADPKD.&lt;ref name=&quot;:0&quot; /&gt;

ADPKD can also result in a wide array of symptoms beyond the kidneys, resulting in the following symptoms:&lt;ref name=&quot;:0&quot; /&gt;&lt;ref name=&quot;:2&quot; /&gt;

* Neurological: Arachnoid cysts, intracranial hemorrhage.
* Cardiovascular: Pericardial effusion, mitral valve prolapse, bicuspid aortic valve
* Endocrine: Pancreatic cysts
* Gastrointestinal: Polycystic liver disease, diverticulosis
* Pulmonary: Bronchiectasis
* Reproductive: Male infertility, seminal vesicle cysts, ovarian cysts

Among the clinical presentation are:{{citation needed|date=September 2021}}
* Acute loin pain
* [[Hematuria|Blood in the urine]]
* Ballotable kidneys
* [[Subarachnoid hemorrhage]] (berry aneurysm)
* [[Hypertension]]
* Associated liver cysts
* Uremia due to [[kidney failure]]
* Anemia due to [[chronic kidney disease]]
* Increase RBC or [[erythropoietin]] secretion

Signs and symptoms of ADPKD often develop between 30 and 40 years of age.&lt;ref&gt;{{cite web |title=Polycystic kidney disease |url=https://www.mayoclinic.org/diseases-conditions/polycystic-kidney-disease/symptoms-causes/syc-20352820 |accessdate=2022-05-23 |website=Mayo Clinic}}&lt;/ref&gt;

==Genetics==

ADPKD is genetically heterogeneous with two [[genes]] identified: ''[[PKD1]]'' (chromosome region 16p13.3; around 85% cases) &lt;ref&gt;{{Cite journal |last1=Somlo |first1=Stefan |last2=Wirth |first2=Brunhilde |last3=Germino |first3=Gregory G. |last4=Weinstat-Saslow |first4=Debra |last5=Gillespie |first5=Gerald A. J. |last6=Himmelbauer |first6=Heinz |last7=Steevens |first7=Laura |last8=Coucke |first8=Paul |last9=Willems |first9=Patrick |last10=Bachner |first10=Lucien |last11=Coto |first11=Eliecer |last12=López-Larrea |first12=Carlos |last13=Peral |first13=Bélen |last14=Millán |first14=JoséLuis San |last15=Saris |first15=Jasper J. |date=1992-05-01 |title=Fine genetic localization of the gene for autosomal dominant polycystic kidney disease (PKD1) with respect to physically mapped markers |url=https://dx.doi.org/10.1016/0888-7543%2892%2990215-E |journal=Genomics |volume=13 |issue=1 |pages=152–158 |doi=10.1016/0888-7543(92)90215-E |pmid=1349570 |issn=0888-7543|url-access=subscription |hdl=10651/41361 |hdl-access=free }}&lt;/ref&gt; and'' [[PKD2]]'' (4q21; around 15% cases).&lt;ref&gt;{{Cite journal |last1=Kimberling |first1=William J. |last2=Kumar |first2=Shrawan |last3=Gabow |first3=Patricia A. |last4=Kenyon |first4=Judith B. |last5=Connolly |first5=Christopher J. |last6=Somlo |first6=Stefan |date=1993-12-01 |title=Autosomal dominant polycystic kidney disease: Localization of the second gene to chromosome 4q13–q23 |url=https://www.sciencedirect.com/science/article/pii/S0888754311800017 |journal=Genomics |volume=18 |issue=3 |pages=467–472 |doi=10.1016/S0888-7543(11)80001-7 |pmid=8307555 |issn=0888-7543|url-access=subscription }}&lt;/ref&gt;&lt;ref&gt;{{Cite journal |last1=Kumar |first1=Shrawan |last2=Kimberling |first2=William J. |last3=Gabow |first3=Patricia A. |last4=Kenyon |first4=Judy B. |date=1991-06-01 |title=Genetic linkage studies of autosomal dominant polycystic kidney disease: search for the second gene in a large Sicilian family |url=https://doi.org/10.1007/BF00204167 |journal=Human Genetics |language=en |volume=87 |issue=2 |pages=129–133 |doi=10.1007/BF00204167 |pmid=1676697 |issn=1432-1203|url-access=subscription }}&lt;/ref&gt;&lt;ref name=&quot;TP-150518-E20&quot; /&gt; Several genetic mechanisms probably contribute to the [[phenotype|phenotypic]] expression of the disease.&lt;ref name=&quot;TP-150518-E20&quot; /&gt; Although  evidence exists for a two-hit mechanism (germline and somatic inactivation of two PKD alleles) explaining the focal development of renal and hepatic cysts,&lt;ref name=&quot;TP-150518-E22&quot;&gt;{{cite journal | vauthors = Torra R, Badenas C, San Millán JL, Pérez-Oller L, Estivill X, Darnell A | title = A loss-of-function model for cystogenesis in human autosomal dominant polycystic kidney disease type 2 | journal = American Journal of Human Genetics | volume = 65 | issue = 2 | pages = 345–352 | date = August 1999 | pmid = 10417277 | pmc = 1377933 | doi = 10.1086/302501 }}&lt;/ref&gt;&lt;ref name=&quot;TP-150518-E23&quot;&gt;{{cite journal | vauthors = Watnick TJ, Torres VE, Gandolph MA, Qian F, Onuchic LF, Klinger KW, Landes G, Germino GG | display-authors = 6 | title = Somatic mutation in individual liver cysts supports a two-hit model of cystogenesis in autosomal dominant polycystic kidney disease | journal = Molecular Cell | volume = 2 | issue = 2 | pages = 247–251 | date = August 1998 | pmid = 9734362 | doi = 10.1016/s1097-2765(00)80135-5 | doi-access = free }}&lt;/ref&gt; [[haploinsufficiency]] is more likely to account for the vascular manifestations of the disease.&lt;ref name=&quot;TP-150518-E24&quot;&gt;{{cite journal | vauthors = Qian Q, Hunter LW, Li M, Marin-Padilla M, Prakash YS, Somlo S, Harris PC, Torres VE, Sieck GC | display-authors = 6 | title = Pkd2 haploinsufficiency alters intracellular calcium regulation in vascular smooth muscle cells | journal = Human Molecular Genetics | volume = 12 | issue = 15 | pages = 1875–1880 | date = August 2003 | pmid = 12874107 | doi = 10.1093/hmg/ddg190 | doi-access = free }}&lt;/ref&gt;&lt;ref name=&quot;TP-150518-E25&quot;&gt;{{cite journal | vauthors = Gao Z, Joseph E, Ruden DM, Lu X | title = Drosophila Pkd2 is haploid-insufficient for mediating optimal smooth muscle contractility | journal = The Journal of Biological Chemistry | volume = 279 | issue = 14 | pages = 14225–14231 | date = April 2004 | pmid = 14732716 | doi = 10.1074/jbc.M312223200 | doi-access = free }}&lt;/ref&gt; Additionally, new mouse models homozygous for ''PKD1'' hypomorphic alleles 22 and 23 and the demonstration of increased renal epithelial cell proliferation in PKD2 +/− mice suggest that mechanisms other than the two-hit hypothesis also contribute to the cystic phenotype.&lt;ref name=&quot;TP-150518-E20&quot; /&gt;

Large interfamilial and intrafamilial variability occurs in ADPKD.&lt;ref name=&quot;TP-150518-E20&quot; /&gt; Most individuals with ''PKD1'' mutations have kidney failure by age 70 years, whereas more than 50% of individuals with'' PKD2'' mutations have adequate renal function at that age (mean age of onset of end-stage renal disease: 54·3 years with ''PKD1''; 74·0 years with ''PKD2'').&lt;ref name=&quot;TP-150518-E26&quot;&gt;{{cite journal | vauthors = Hateboer N, v Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL, Torra R, Breuning M, Ravine D | display-authors = 6 | title = Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group | journal = Lancet | volume = 353 | issue = 9147 | pages = 103–107 | date = January 1999 | pmid = 10023895 | doi = 10.1016/s0140-6736(98)03495-3 | s2cid = 30757096 }}&lt;/ref&gt;

The significant intrafamilial variability observed in the severity of renal and extrarenal manifestations points to genetic and environmental modifying factors that may influence the outcome of ADPKD, and results of an analysis of the variability in renal function between monozygotic twins and siblings support the role of [[Modifier gene|genetic modifiers]] in this disease.&lt;ref name=&quot;TP-150518-E20&quot; /&gt;&lt;ref name=&quot;TP-150518-E27&quot;&gt;{{cite journal | vauthors = Persu A, Duyme M, Pirson Y, Lens XM, Messiaen T, Breuning MH, Chauveau D, Levy M, Grünfeld JP, Devuyst O | display-authors = 6 | title = Comparison between siblings and twins supports a role for modifier genes in ADPKD | journal = Kidney International | volume = 66 | issue = 6 | pages = 2132–2136 | date = December 2004 | pmid = 15569302 | doi = 10.1111/j.1523-1755.2004.66003.x | doi-access = free }}&lt;/ref&gt; It is estimated that 43–78% of the variance in age to ESRD could be due to heritable modifying factors,&lt;ref name=&quot;TP-150518-E28&quot;&gt;{{cite journal | vauthors = Fain PR, McFann KK, Taylor MR, Tison M, Johnson AM, Reed B, Schrier RW | title = Modifier genes play a significant role in the phenotypic expression of PKD1 | journal = Kidney International | volume = 67 | issue = 4 | pages = 1256–1267 | date = April 2005 | pmid = 15780078 | doi = 10.1111/j.1523-1755.2005.00203.x | doi-access = free }}&lt;/ref&gt;&lt;ref name=&quot;TP-150518-E29&quot;&gt;{{cite journal | vauthors = Paterson AD, Magistroni R, He N, Wang K, Johnson A, Fain PR, Dicks E, Parfrey P, St George-Hyslop P, Pei Y | display-authors = 6 | title = Progressive loss of renal function is an age-dependent heritable trait in type 1 autosomal dominant polycystic kidney disease | journal = Journal of the American Society of Nephrology | volume = 16 | issue = 3 | pages = 755–762 | date = March 2005 | pmid = 15677307 | doi = 10.1681/ASN.2004090758 | doi-access = free | hdl = 11380/307038 | hdl-access = free }}&lt;/ref&gt; with parents as likely as children to show more severe disease in studies of parent-child pairs.&lt;ref name=&quot;TP-150518-E20&quot; /&gt;&lt;ref name=&quot;TP-150518-E30&quot;&gt;{{cite journal | vauthors = Geberth S, Ritz E, Zeier M, Stier E | title = Anticipation of age at renal death in autosomal dominant polycystic kidney disease (ADPKD)? | journal = Nephrology, Dialysis, Transplantation | volume = 10 | issue = 9 | pages = 1603–1606 | year = 1995 | pmid = 8559477 }}&lt;/ref&gt;

==Pathophysiology==

In many patients with ADPKD, kidney dysfunction is not clinically apparent until 30 or 40 years of age.&lt;ref name=&quot;grantham&quot;/&gt; However, an increasing body of evidence suggests the formation of renal cysts starts ''in utero''.&lt;ref name=&quot;TP-150518-E31&quot;&gt;{{cite journal | vauthors = Paul BM, Vanden Heuvel GB | title = Kidney: polycystic kidney disease | journal = Wiley Interdisciplinary Reviews. Developmental Biology | volume = 3 | issue = 6 | pages = 465–487 | year = 2014 | pmid = 25186187 | pmc = 4423807 | doi = 10.1002/wdev.152 }}&lt;/ref&gt; Cysts initially form as small dilations in renal tubules, which then expand to form fluid-filled cavities of different sizes.&lt;ref name=&quot;TP-150518-E31&quot; /&gt; Factors suggested to lead to cystogenesis include a [[germline mutation]] in one of the polycystin gene alleles, a somatic second hit that leads to the loss of the normal allele, and a third hit, which can be a renal insult that triggers cell proliferation, and an injury response.&lt;ref&gt;{{cite journal | vauthors = Weimbs T | title = Third-hit signaling in renal cyst formation | journal = Journal of the American Society of Nephrology | volume = 22 | issue = 5 | pages = 793–795 | date = May 2011 | pmid = 21493772 | pmc = 5619655 | doi = 10.1681/ASN.2011030284 }}&lt;/ref&gt; Due to numerous similarities between the pathophysiology of ADPKD and the pathophysiology of the renal response to injury, ADPKD has been described as a state of aberrant and persistent activation of renal injury response pathways.&lt;ref&gt;{{cite journal | vauthors = Weimbs T | title = Polycystic kidney disease and renal injury repair: common pathways, fluid flow, and the function of polycystin-1 | journal = American Journal of Physiology. Renal Physiology | volume = 293 | issue = 5 | pages = F1423–F1432 | date = November 2007 | pmid = 17715262 | doi = 10.1152/ajprenal.00275.2007 }}&lt;/ref&gt; In the progression of the disease, continued dilation of the tubules through increased cell proliferation, fluid secretion, and separation from the parental tubule lead to the formation of cysts.&lt;ref name=&quot;TP-150518-E32&quot;&gt;{{cite journal | vauthors = Igarashi P, Somlo S | title = Genetics and pathogenesis of polycystic kidney disease | journal = Journal of the American Society of Nephrology | volume = 13 | issue = 9 | pages = 2384–2398 | date = September 2002 | pmid = 12191984 | doi = 10.1097/01.asn.0000028643.17901.42 | doi-access = free }}&lt;/ref&gt;&lt;ref name=&quot;TP-150518-E37&quot;&gt;{{cite journal | vauthors = Parnell SC, Magenheimer BS, Maser RL, Zien CA, Frischauf AM, Calvet JP | title = Polycystin-1 activation of c-Jun N-terminal kinase and AP-1 is mediated by heterotrimeric G proteins | journal = The Journal of Biological Chemistry | volume = 277 | issue = 22 | pages = 19566–19572 | date = May 2002 | pmid = 11912216 | doi = 10.1074/jbc.M201875200 | doi-access = free }}&lt;/ref&gt;

ADPKD, together with many other diseases that present with renal cysts, can be classified into a family of diseases known as [[ciliopathy|ciliopathies]].&lt;ref name=&quot;TP-150518-E33&quot;&gt;{{cite journal | vauthors = Berbari NF, O'Connor AK, Haycraft CJ, Yoder BK | title = The primary cilium as a complex signaling center | journal = Current Biology | volume = 19 | issue = 13 | pages = R526–R535 | date = July 2009 | pmid = 19602418 | pmc = 2814769 | doi = 10.1016/j.cub.2009.05.025 | bibcode = 2009CBio...19.R526B }}&lt;/ref&gt; Epithelial cells of the renal tubules, including all the segments of the nephron and the collecting ducts (with the exception of intercalated cells) show the presence of a single primary apical cilium.&lt;ref name=&quot;TP-150518-E34&quot;&gt;{{cite journal | vauthors = Reed BY, McFann K, Bekheirnia MR, Reza Bekheirnia M, Nobakhthaghighi N, Nobkhthaghighi N, Masoumi A, Johnson AM, Shamshirsaz AA, Shamshiraz AA, Kelleher CL, Schrier RW | display-authors = 6 | title = Variation in age at ESRD in autosomal dominant polycystic kidney disease | journal = American Journal of Kidney Diseases | volume = 51 | issue = 2 | pages = 173–183 | date = February 2008 | pmid = 18215695 | pmc = 2747334 | doi = 10.1053/j.ajkd.2007.10.037 }}&lt;/ref&gt; [[PKD1|Polycystin-1]], the protein encoded by the [[PKD1]] gene, is present on these cilia and is thought to sense the flow with its large extracellular domains, activating the calcium channels associated with [[PKD2|polycystin-2]], the product of gene [[PKD2]],&lt;ref name=&quot;TP-150518-E35&quot;&gt;{{cite journal | vauthors = Chapin HC, Caplan MJ | title = The cell biology of polycystic kidney disease | journal = The Journal of Cell Biology | volume = 191 | issue = 4 | pages = 701–710 | date = November 2010 | pmid = 21079243 | pmc = 2983067 | doi = 10.1083/jcb.201006173 }}&lt;/ref&gt; as a result of the genetic setting of ADPKD as explained in the '''genetics''' sub-section above.

Epithelial cell proliferation and fluid secretion lead to cystogenesis, which are two hallmark features of ADPKD.&lt;ref name=&quot;TP-150518-E36&quot;&gt;{{cite journal | vauthors = Belibi FA, Reif G, Wallace DP, Yamaguchi T, Olsen L, Li H, Helmkamp GM, Grantham JJ | display-authors = 6 | title = Cyclic AMP promotes growth and secretion in human polycystic kidney epithelial cells | journal = Kidney International | volume = 66 | issue = 3 | pages = 964–973 | date = September 2004 | pmid = 15327388 | doi = 10.1111/j.1523-1755.2004.00843.x | doi-access = free }}&lt;/ref&gt; During the early stages of cystogenesis, cysts are attached to their parental renal tubules and a derivative of the glomerular filtrate enters the cysts.&lt;ref name=&quot;TP-150518-E31&quot; /&gt; Once these cysts expand to approximately 2 mm in diameter, the cyst closes off from its parental tubule and after that fluid can only enter the cysts through transepithelial secretion, which in turn is suggested to increase due to secondary effects from an increased intracellular concentration of [[cyclic AMP]] (cAMP).&lt;ref name=&quot;TP-150518-E31&quot; /&gt;

Clinically, the insidious increase in the number and size of renal cysts translates as a progressive increment in kidney volume.&lt;ref name=&quot;TP-150518-E20&quot; /&gt;&lt;ref name=&quot;TP-150518-E31&quot; /&gt; Studies led by [[Mayo Clinic]] professionals established that the total kidney volume (TKV) in a large cohort of ADPKD patients was 1060 ± 642ml with a mean increase of 204ml over three years, or 5.27% per year in the natural course of the disease, among other important, novel findings that were extensively studied for the first time.&lt;ref name=&quot;TP-150515-017&quot;&gt;{{cite journal | vauthors = Torres VE | title = Treatment strategies and clinical trial design in ADPKD | journal = Advances in Chronic Kidney Disease | volume = 17 | issue = 2 | pages = 190–204 | date = March 2010 | pmid = 20219622 | pmc = 4127876 | doi = 10.1053/j.ackd.2010.01.006 }}&lt;/ref&gt;

[[Image:PKD1PKD2 en.png|thumb|Illustration of PKD1 and PKD2 proteins at the cell membrane]]

==Diagnosis==
Usually, the diagnosis of ADPKD is initially performed by renal imaging using [[ultrasound]], [[CT scan]], or [[MRI]].&lt;ref name=&quot;TP-150519-E40&quot;&gt;{{cite journal | vauthors = Trujillano D, Bullich G, Ossowski S, Ballarín J, Torra R, Estivill X, Ars E | title = Diagnosis of autosomal dominant polycystic kidney disease using efficient PKD1 and PKD2 targeted next-generation sequencing | journal = Molecular Genetics &amp; Genomic Medicine | volume = 2 | issue = 5 | pages = 412–421 | date = September 2014 | pmid = 25333066 | pmc = 4190876 | doi = 10.1002/mgg3.82 }}&lt;/ref&gt; However, molecular diagnostics can be necessary in the following situations: '''''1-''''' when a definite diagnosis is required in young individuals, such as a potential living related donor in an affected family with equivocal imaging data;&lt;ref name=&quot;TP-150519-E40&quot; /&gt; '''''2-''''' in patients with a negative family history of ADPKD, because of potential phenotypic overlap with several other kidney cystic diseases;&lt;ref name=&quot;TP-150519-E40&quot; /&gt; '''''3-''''' in families affected by early-onset polycystic kidney disease, since in this cases [[Hypomorphic mutation|hypomorphic alleles]] and/or [[oligogenic inheritance]] can be involved;&lt;ref name=&quot;TP-150519-E40&quot; /&gt;&lt;ref name=&quot;TP-150519-E41&quot;&gt;{{cite journal | vauthors = Bergmann C, von Bothmer J, Ortiz Brüchle N, Venghaus A, Frank V, Fehrenbach H, Hampel T, Pape L, Buske A, Jonsson J, Sarioglu N, Santos A, Ferreira JC, Becker JU, Cremer R, Hoefele J, Benz MR, Weber LT, Buettner R, Zerres K | display-authors = 6 | title = Mutations in multiple PKD genes may explain early and severe polycystic kidney disease | journal = Journal of the American Society of Nephrology | volume = 22 | issue = 11 | pages = 2047–2056 | date = November 2011 | pmid = 22034641 | pmc = 3279997 | doi = 10.1681/ASN.2010101080 }}&lt;/ref&gt; and '''''4-''''' in patients requesting [[genetic counseling]], especially in couples wishing a pre-implantation [[genetic diagnosis]].&lt;ref name=&quot;TP-150519-E40&quot; /&gt;&lt;ref name=&quot;TP-150519-E42&quot;&gt;{{cite journal | vauthors = Harris PC, Rossetti S | title = Molecular diagnostics for autosomal dominant polycystic kidney disease | journal = Nature Reviews. Nephrology | volume = 6 | issue = 4 | pages = 197–206 | date = April 2010 | pmid = 20177400 | pmc = 4050432 | doi = 10.1038/nrneph.2010.18 }}&lt;/ref&gt;

The findings of large [[Radioopaque|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 provides presumptively, but not definitively, evidence for the diagnosis. In some cases, intracranial aneurysms can be an associated sign of ADPKD, and screening can be recommended for patients with a family history of intracranial aneurysms.&lt;ref name=&quot;TP-150818-01&quot;&gt;{{cite journal | vauthors = Rozenfeld MN, Ansari SA, Shaibani A, Russell EJ, Mohan P, Hurley MC | title = Should patients with autosomal dominant polycystic kidney disease be screened for cerebral aneurysms? | journal = AJNR. American Journal of Neuroradiology | volume = 35 | issue = 1 | pages = 3–9 | date = January 2014 | pmid = 23292526 | pmc = 7966475 | doi = 10.3174/ajnr.A3437 | s2cid = 5777115 | doi-access = free }}&lt;/ref&gt;

Molecular [[genetic testing]] by [[linkage analysis]] or direct mutation screening is clinically available; 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]]. 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.{{citation needed|date=June 2016}}

&lt;gallery&gt;
Image:Adult Polycystic Kidney.jpg|Adult polycystic kidney
File:Autosomal Dominant Polycystic Kidney Disease.svg|Diagram of autosomal dominant polycystic disease with a normal kidney inset for comparison
File:CT scan autosomal dominant polycystic kidney disease.jpg|Abdominal CT scan of an adult with autosomal dominant polycystic kidney disease: Extensive cyst formation is seen over both kidneys, with a few cysts in the liver, as well. ([[Coronal plane]])
&lt;/gallery&gt;

==Treatment==
Currently, the only pharmacological treatment available for ADPKD consists of reducing the rate of gain of total kidney volume (TKV) with vasopressin receptor 2 (V2) antagonists (i.e., tolvaptan).&lt;ref&gt;{{cite web |url=https://www.lecturio.com/concepts/autosomal-dominant-polycystic-kidney-disease/ | title= Autosomal Dominant Polycystic Kidney Disease |website= The Lecturio Medical Concept Library |access-date= 3 July 2021}}&lt;/ref&gt; Tolvaptan treatment does not halt or reverse disease progression, and patients still progress towards renal failure.  Palliative treatment modalities involve symptomatic medications (nonopioid and opioid analgesics) for abdominal/retroperitoneal pain. Options for analgesic-resistant pain include simple or complex surgical procedures (i.e., renal cyst aspiration, cyst decortication, renal denervation, and nephrectomy), which can result in complications inherent to surgery.{{citation needed|date=June 2016}} Recent research suggests that ketogenic dietary interventions beneficially affect the progression and symptoms in individuals with ADPKD.&lt;ref name = &quot;Strubl_2021&quot;&gt;{{cite journal | vauthors = Strubl S, Oehm S, Torres JA, Grundmann F, Haratani J, Decker M, Vuong S, Kaur Bhandal A, Methot N, Haynie-Cion R, Meyer F | display-authors = 6 | title = Ketogenic dietary interventions in autosomal dominant polycystic kidney disease—a retrospective case series study: first insights into feasibility, safety and effects. | journal = Clinical Kidney Journal | date = 2021  | volume = 15 | issue = 6 | pages = 1079–1092 |doi= 10.1093/ckj/sfab162 | pmid = 35664270 | pmc = 9155228 }}&lt;/ref&gt;  Mild weight loss favorably affects pain&lt;ref&gt;{{cite journal | vauthors = Nowak KL, Murray K, You Z, Gitomer B, Brosnahan G, Abebe KZ, Braun W, Chapman A, Harris PC, Miskulin D, Perrone R, Torres V, Steinman T, Yu A, Chonchol M | display-authors = 6 | title = Pain and Obesity in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis of the Halt Progression of Polycystic Kidney Disease (HALT-PKD) Studies | journal = Kidney Medicine | volume = 3 | issue = 4 | pages = 536–545.e1 | date = July 1, 2021 | pmid = 34401721 | pmc = 8350824 | doi = 10.1016/j.xkme.2021.03.004 }}&lt;/ref&gt; indicating the benefit of dietary and lifestyle changes.

===Aquaretic medication===
In 2014, Japan was the first country in the world to approve a pharmacological treatment for ADPKD&lt;ref name=&quot;TP-150515-017&quot; /&gt; followed by Canada and Europe, which approved the drug [[tolvaptan]] for ADPKD patients at the beginning of 2015.  The USA FDA approved the use of tolvaptan in the treatment of ADPKD in 2018.&lt;ref&gt;{{Cite web | url=https://www.renalandurologynews.com/chronic-kidney-disease-ckd/tolvaptan-receives-fda-approved-for-treating-adpkd-in-adults/article/761347/ | title=Tolvaptan Cleared in US for ADPKD in Adults| work=Renal and Urology News| date=2018-04-26}}&lt;/ref&gt; Tolvaptan, an [[aquaretic]] drug, is a [[vasopressin receptor]] 2 (V2) [[antagonist drug|antagonist]].&lt;ref name=&quot;TP-150514-004&quot; /&gt; Pre-clinical studies had suggested that the molecule [[Cyclic AMP|cAMP]] could be involved in the enlargement of ADPKD cysts,&lt;ref name=&quot;Hanaoka and Guggino&quot;&gt;{{cite journal | vauthors = Hanaoka K, Guggino WB | title = cAMP regulates cell proliferation and cyst formation in autosomal polycystic kidney disease cells | journal = Journal of the American Society of Nephrology | volume = 11 | issue = 7 | pages = 1179–1187 | date = July 2000 | pmid = 10864573 | doi = 10.1681/ASN.V1171179 | doi-access = free }}&lt;/ref&gt; and studies on rodents confirmed the role of [[vasopressin]] in increasing the levels of cAMP in the kidney, which laid the basis for the conduction of clinical studies.&lt;ref name=&quot;TP-150519-E44&quot;&gt;{{cite journal | vauthors = Juul KV, Bichet DG, Nielsen S, Nørgaard JP | title = The physiological and pathophysiological functions of renal and extrarenal vasopressin V2 receptors | journal = American Journal of Physiology. Renal Physiology | volume = 306 | issue = 9 | pages = F931–F940 | date = May 2014 | pmid = 24598801 | doi = 10.1152/ajprenal.00604.2013 }}&lt;/ref&gt; Because data from the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) led by [[Mayo Clinic]] showed that total kidney volume (TKV) predicted the risk of developing [[chronic kidney disease]] in patients with ADPKD,&lt;ref name=&quot;TP-150515-017&quot; /&gt;&lt;ref name=&quot;TP-150519-E39&quot;&gt;{{cite journal | vauthors = Irazabal MV, Rangel LJ, Bergstralh EJ, Osborn SL, Harmon AJ, Sundsbak JL, Bae KT, Chapman AB, Grantham JJ, Mrug M, Hogan MC, El-Zoghby ZM, Harris PC, Erickson BJ, King BF, Torres VE | display-authors = 6 | title = Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials | journal = Journal of the American Society of Nephrology | volume = 26 | issue = 1 | pages = 160–172 | date = January 2015 | pmid = 24904092 | pmc = 4279733 | doi = 10.1681/ASN.2013101138 }}&lt;/ref&gt; the TEMPO 3:4 trial, which enrolled patients from 129 sites worldwide from 2007 to 2009, evaluated TKV as a [[Clinical endpoint|primary end-point]] to test the efficacy of tolvaptan in ADPKD patients.&lt;ref name=&quot;TP-150514-004&quot; /&gt;&lt;ref name=&quot;TP-150514-005&quot; /&gt; That study showed a significant decrease in the ratio of TKV increase and deterring of [[renal function]] decline in ADPKD patients after treatment with tolvaptan;&lt;ref name=&quot;TP-150514-004&quot; /&gt;&lt;ref name=&quot;TP-150515-007&quot;&gt;{{cite journal | vauthors = Kelsey R | title = Polycystic kidney disease: Tolvaptan in ADPKD-TEMPO 3:4 trial results | journal = Nature Reviews. Nephrology | volume = 9 | issue = 1 | pages = 1 | date = January 2013 | pmid = 23183839 | doi = 10.1038/nrneph.2012.236 | s2cid = 22942772 | doi-access = free }}&lt;/ref&gt; however, because laboratory test results regarding [[liver function]] appeared elevated in a percentage of patients enrolled in that study, the approval of the drug was either delayed by regulatory agencies or, as in case of the US, altogether denied.&lt;ref name=&quot;TP-150514-005&quot; /&gt;&lt;ref name=&quot;TP-150515-012&quot;&gt;{{cite journal |author= Brown T |title= Tolvaptan Not Recommended for ADPKD |journal= Medscape |year= 2013 |url= http://www.medscape.com/viewarticle/809028}}&lt;/ref&gt;

===Dietary and lifestyle interventions===
Research using ADPKD mouse models showed that mild food restriction strongly improved disease progression.&lt;ref&gt;{{cite journal | vauthors = Kipp KR, Rezaei M, Lin L, Dewey EC, Weimbs T | title = A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease | journal = American Journal of Physiology. Renal Physiology | volume = 310 | issue = 8 | pages = F726–F731 | date = April 2016 | pmid = 26764208 | pmc = 4835927 | doi = 10.1152/ajprenal.00551.2015 }}&lt;/ref&gt; The mechanism was shown to involve the metabolic state of [[ketosis]], and beneficial effects could be produced by time-restricted feeding, acute fasting, a ketogenic diet, or by supplementation with the ketone [[beta-hydroxybutyrate]] in mouse, rat and cat models of ADPKD.&lt;ref name=&quot;rat model&quot;&gt;{{cite journal | vauthors = Torres JA, Kruger SL, Broderick C, Amarlkhagva T, Agrawal S, Dodam JR, Mrug M, Lyons LA, Weimbs T | display-authors = 6 | title = Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease | journal = Cell Metabolism | volume = 30 | issue = 6 | pages = 1007–1023.e5 | date = December 2019 | pmid = 31631001 | pmc = 6904245 | doi = 10.1016/j.cmet.2019.09.012 }}&lt;/ref&gt;&lt;ref name=&quot;ketosis&quot;&gt;{{cite journal | vauthors = Carney EF | title = Ketosis slows the progression of PKD | journal = Nature Reviews. Nephrology | volume = 16 | issue = 1 | pages = 1 | date = January 2020 | pmid = 31654043 | doi = 10.1038/s41581-019-0226-4 | s2cid = 204886698 | doi-access = free }}&lt;/ref&gt;  A ketogenic diet regimen not only halted further disease progression but led to partial reversal of renal cystic disease in a rat model.&lt;ref name=&quot;ketosis&quot;/&gt; The metabolic state of ketosis may be beneficial in ADPKD because renal cyst cells in ADPKD have a metabolic defect similar to the [[Warburg effect (oncology)|Warburg effect]] in cancer that makes them highly dependent on glucose, and unable to metabolize fatty acids and ketones.&lt;ref name=&quot;rat model&quot; /&gt;&lt;ref&gt;{{cite journal | vauthors = Nowak KL, Hopp K | title = Metabolic Reprogramming in Autosomal Dominant Polycystic Kidney Disease: Evidence and Therapeutic Potential | journal = Clinical Journal of the American Society of Nephrology | volume = 15 | issue = 4 | pages = 577–584 | date = April 2020 | pmid = 32086281 | pmc = 7133124 | doi = 10.2215/CJN.13291019 }}&lt;/ref&gt;&lt;ref&gt;{{cite journal | vauthors = Padovano V, Podrini C, Boletta A, Caplan MJ | title = Metabolism and mitochondria in polycystic kidney disease research and therapy | journal = Nature Reviews. Nephrology | volume = 14 | issue = 11 | pages = 678–687 | date = November 2018 | pmid = 30120380 | doi = 10.1038/s41581-018-0051-1 | s2cid = 52033674 }}&lt;/ref&gt; Consistent with this, serum glucose levels positively correlate with faster disease progression in ADPKD patients.&lt;ref&gt;{{cite journal | vauthors = Torres JA, Kruger SL, Broderick C, Amarlkhagva T, Agrawal S, Dodam JR, Mrug M, Lyons LA, Weimbs T | display-authors = 6 | title = Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease | journal = Cell Metabolism | volume = 30 | issue = 6 | pages = 1007–1023.e5 | date = December 2019 | pmid = 31631001 | pmc = 6904245 | doi = 10.1016/j.cmet.2019.09.012 | ref = glucose levels }}&lt;/ref&gt; Also, individuals with ADPKD and type 2 diabetes have significantly larger total kidney volume (TKV) than those with ADPKD alone,&lt;ref&gt;{{cite journal | vauthors = Reed B, Helal I, McFann K, Wang W, Yan XD, Schrier RW | title = The impact of type II diabetes mellitus in patients with autosomal dominant polycystic kidney disease | journal = Nephrology, Dialysis, Transplantation | volume = 27 | issue = 7 | pages = 2862–2865 | date = July 2012 | pmid = 22207329 | pmc = 3398061 | doi = 10.1093/ndt/gfr744 }}&lt;/ref&gt; and overweight or obesity associate with faster progression in early-stage ADPKD.&lt;ref&gt;{{cite journal | vauthors = Nowak KL, You Z, Gitomer B, Brosnahan G, Torres VE, Chapman AB, Perrone RD, Steinman TI, Abebe KZ, Rahbari-Oskoui FF, Yu AS, Harris PC, Bae KT, Hogan M, Miskulin D, Chonchol M | display-authors = 6 | title = Overweight and Obesity Are Predictors of Progression in Early Autosomal Dominant Polycystic Kidney Disease | journal = Journal of the American Society of Nephrology | volume = 29 | issue = 2 | pages = 571–578 | date = February 2018 | pmid = 29118087 | pmc = 5791072 | doi = 10.1681/ASN.2017070819 }}&lt;/ref&gt; A retrospective case series study showed that ADPKD disease symptoms - including pain, hypertension and renal function - improved among 131 patients who implemented ketogenic diets for an average duration of 6 months.&lt;ref name = &quot;Strubl_2021&quot; /&gt;

Dietary intake of sodium is associated with worse renal function decline in ADPKD,&lt;ref&gt;{{cite journal | vauthors = Kramers BJ, Koorevaar IW, Drenth JP, de Fijter JW, Neto AG, Peters DJ, Vart P, Wetzels JF, Zietse R, Gansevoort RT, Meijer E | display-authors = 6 | title = Salt, but not protein intake, is associated with accelerated disease progression in autosomal dominant polycystic kidney disease | journal = Kidney International | volume = 98 | issue = 4 | pages = 989–998 | date = October 2020 | pmid = 32534051 | doi = 10.1016/j.kint.2020.04.053 | s2cid = 219637514 | doi-access = free | hdl = 2066/225147 | hdl-access = free }}&lt;/ref&gt; and limiting sodium intake is generally recommended to patients. Dietary protein intake was not found to correlate with ADPKD progression.&lt;ref&gt;{{cite journal | vauthors = Kramers BJ, Koorevaar IW, Drenth JP, de Fijter JW, Neto AG, Peters DJ, Vart P, Wetzels JF, Zietse R, Gansevoort RT, Meijer E | display-authors = 6 | title = Salt, but not protein intake, is associated with accelerated disease progression in autosomal dominant polycystic kidney disease | journal = Kidney International | volume = 98 | issue = 4 | pages = 989–998 | date = October 2020 | pmid = 32534051 | doi = 10.1016/j.kint.2020.04.053 | s2cid = 219637514 | first8 = Priya | first6 = A.G. | first7 = D.J.M. | doi-access = free | hdl = 2066/225147 | hdl-access = free }}&lt;/ref&gt;

Increased water intake is thought to be beneficial in ADPKD and is generally recommended.&lt;ref name = &quot;Torres_2019&quot;&gt;{{cite journal | vauthors = Torres JA, Rezaei M, Broderick C, Lin L, Wang X, Hoppe B, Cowley BD, Savica V, Torres VE, Khan S, Holmes RP, Mrug M, Weimbs T | display-authors = 6 | title = Crystal deposition triggers tubule dilation that accelerates cystogenesis in polycystic kidney disease | journal = The Journal of Clinical Investigation | volume = 129 | issue = 10 | pages = 4506–4522 | date = July 2019 | pmid = 31361604 | pmc = 6763267 | doi = 10.1172/JCI128503 }}&lt;/ref&gt;&lt;ref&gt;{{cite journal | vauthors = Amro OW, Paulus JK, Noubary F, Perrone RD | title = Low-Osmolar Diet and Adjusted Water Intake for Vasopressin Reduction in Autosomal Dominant Polycystic Kidney Disease: A Pilot Randomized Controlled Trial | journal = American Journal of Kidney Diseases | volume = 68 | issue = 6 | pages = 882–891 | date = December 2016 | pmid = 27663039 | pmc = 5123924 | doi = 10.1053/j.ajkd.2016.07.023 }}&lt;/ref&gt; The underlying beneficial mechanism of increased water intake may be related to effects on the vasopressin V2 receptor or may be due to the suppression of harmful micro-crystal formation in renal tubules by dilution of solutes such as calcium oxalate, calcium phosphate, and uric acid.&lt;ref name = &quot;Torres_2019&quot; /&gt;&lt;ref&gt;{{cite journal | vauthors = Allison SJ | title = Crystal deposition aids cystogenesis | journal = Nature Reviews. Nephrology | volume = 15 | issue = 12 | pages = 730 | date = December 2019 | pmid = 31551591 | doi = 10.1038/s41581-019-0215-7 | s2cid = 202733384 | doi-access = free }}&lt;/ref&gt;

Dietary intake of oxalate or inorganic phosphate has been shown to accelerate PKD disease progression in several rodent models.&lt;ref name = &quot;Torres_2019&quot; /&gt; Low levels, or urinary citrate – a natural antagonist of the formation of harmful crystals in kidney tubules – have been shown to associate with worse disease progression in ADPKD patients.&lt;ref name = &quot;Torres_2019&quot; /&gt;

===Analgesic medication===
[[Chronic pain]] in patients with ADPKD is often refractory to conservative, noninvasive treatments, but [[Nonsteroidal anti-inflammatory drug|nonopioid analgesics]] and conservative interventions can be first used before [[opioid analgesic]]s are considered; if pain continues, then surgical interventions can target renal or hepatic cysts to directly address the cause of pain, with surgical options including renal cyst decortication, renal [[denervation]], and [[nephrectomy]].&lt;ref name=&quot;TP-150515-E02&quot;&gt;{{cite journal | vauthors = Tellman MW, Bahler CD, Shumate AM, Bacallao RL, Sundaram CP | title = Management of pain in autosomal dominant polycystic kidney disease and anatomy of renal innervation | journal = The Journal of Urology | volume = 193 | issue = 5 | pages = 1470–1478 | date = May 2015 | pmid = 25534330 | doi = 10.1016/j.juro.2014.10.124 | hdl-access = free | hdl = 1805/7798 }}&lt;/ref&gt;

===Renal cyst aspiration===
Aspiration with ethanol [[sclerotherapy]] can be performed for the treatment of symptomatic simple renal cysts, but can be impractical in advanced patients with multiple cysts.&lt;ref name=&quot;TP-150515-E03&quot;&gt;{{cite journal | vauthors = Mohsen T, Gomha MA | title = Treatment of symptomatic simple renal cysts by percutaneous aspiration and ethanol sclerotherapy | journal = BJU International | volume = 96 | issue = 9 | pages = 1369–1372 | date = December 2005 | pmid = 16287460 | doi = 10.1111/j.1464-410X.2005.05851.x | doi-access = free }}&lt;/ref&gt; The procedure itself consists in the percutaneous insertion of a needle into the identified cyst, under [[ultrasound]] guidance, with subsequent draining the contained liquid; the sclerotherapy is used to avoid liquid reaccumulation that can occur in the cyst, which can result in symptom recurrence.&lt;ref name=&quot;TP-150515-E03&quot; /&gt;&lt;ref name=&quot;TP-150515-E07&quot;&gt;{{cite journal | vauthors = Okeke AA, Mitchelmore AE, Keeley FX, Timoney AG | title = A comparison of aspiration and sclerotherapy with laparoscopic de-roofing in the management of symptomatic simple renal cysts | journal = BJU International | volume = 92 | issue = 6 | pages = 610–613 | date = October 2003 | pmid = 14511045 | doi = 10.1046/j.1464-410x.2003.04417.x | doi-access = free }}&lt;/ref&gt;

===Laparoscopic cyst decortication===
Laparoscopic cyst decortication (also referred to as marsupialization) consists of the removal of one or more kidney cysts through [[laparoscopic surgery]], during which cysts are punctured, and the outer wall of the larger cysts is excised with care not to incise the renal parenchyma.&lt;ref name=&quot;TP-150515-E04&quot;&gt;{{cite journal | vauthors = Brown JA, Torres VE, King BF, Segura JW | title = Laparoscopic marsupialization of symptomatic polycystic kidney disease | journal = The Journal of Urology | volume = 156 | issue = 1 | pages = 22–27 | date = July 1996 | pmid = 8648810 | doi = 10.1016/s0022-5347(01)65927-5 }}&lt;/ref&gt;&lt;ref name=&quot;TP-150515-E05&quot;&gt;{{cite journal | vauthors = McDougall EM | title = Approach to decortication of simple cysts and polycystic kidneys | journal = Journal of Endourology | volume = 14 | issue = 10 | pages = 821–827 | date = December 2000 | pmid = 11206615 | doi = 10.1089/end.2000.14.821 }}&lt;/ref&gt; This procedure can be useful for pain relief in patients with ADPKD, and is usually indicated after earlier cyst aspiration has confirmed that the cyst to be decorticated is responsible for pain.&lt;ref name=&quot;TP-150515-E05&quot; /&gt;
Nonrandomised controlled trials conducted in the '90s showed that patients with symptomatic simple renal cysts who had recurrence of symptoms after initial response to simple aspiration could be safely submitted to cyst decortication, with a mean pain-free life between 17 and 24 months after surgery.&lt;ref name=&quot;TP-150515-E04&quot; /&gt;&lt;ref name=&quot;TP-150515-E06&quot;&gt;{{cite journal | vauthors = Consonni P, Nava L, Scattoni V, Bianchi A, Spaliviero M, Guazzoni G, Bellinzoni P, Bocciardi A, Rigatti P | display-authors = 6 | title = [Percutaneous echo-guided drainage and sclerotherapy of symptomatic renal cysts: critical comparison with laparoscopic treatment] | journal = Archivio Italiano di Urologia, Andrologia | volume = 68 | issue = 5 Suppl | pages = 27–30 | date = December 1996 | pmid = 9162369 }}&lt;/ref&gt; Laparoscopic decortication presents a 5% recurrence rate of renal cysts compared to an 82% recurrence rate obtained with sclerotherapy.&lt;ref name=&quot;TP-150515-E07&quot; /&gt;

===Neurolysis===
A novel treatment of specifically the chronic pain experienced by many with ADPKD is [[Celiac plexus neurolysis]].&lt;ref name=&quot;pmid28159317&quot;&gt;{{cite journal | vauthors = Casteleijn NF, van Gastel MD, Blankestijn PJ, Drenth JP, de Jager RL, Leliveld AM, Stellema R, Wolff AP, Groen GJ, Gansevoort RT | display-authors = 6 | title = Novel treatment protocol for ameliorating refractory, chronic pain in patients with autosomal dominant polycystic kidney disease | journal = Kidney International | volume = 91 | issue = 4 | pages = 972–981 | date = April 2017 | pmid = 28159317 | doi = 10.1016/j.kint.2016.12.007 | doi-access = free }}&lt;/ref&gt;&lt;ref&gt;{{cite journal | vauthors = Nitschke AM, Ray CE | title = Percutaneous neurolytic celiac plexus block | journal = Seminars in Interventional Radiology | volume = 30 | issue = 3 | pages = 318–321 | date = September 2013 | pmid = 24436554 | pmc = 3773031 | doi = 10.1055/s-0033-1353485 }}&lt;/ref&gt;  This involves the chemical ablation of the [[celiac plexus]], to cause a temporary degeneration of targeted nerve fibers. When the nerve fibers degenerate, it causes an interruption in the transmission of nerve signals.  This treatment, when successful, provides significant pain relief for a period ranging from a few days to over a year.  The procedure may be repeated when the affected nerves have healed and the pain returns.&lt;ref&gt;{{cite journal |title=Response to repeat echoendoscopic celiac plexus neurolysis in pancreatic cancer patients: A machine learning approach |journal=Pancreatology |year=2019 |pmid=31375433 |last1=Facciorusso |first1=A. |last2=Del Prete |first2=V. |last3=Antonino |first3=M. |last4=Buccino |first4=V. R. |last5=Muscatiello |first5=N. |volume=19 |issue=6 |pages=866–872 |doi=10.1016/j.pan.2019.07.038 |s2cid=199389236 }}&lt;/ref&gt;

===Nephrectomy===
Many ADPKD patients experience symptomatic sequelae in consequence of the disease, such as cyst [[hemorrhage]], [[flank pain]], recurrent [[infection]]s, [[nephrolithiasis]], and symptoms of mass effect (i.e., early [[satiety]], [[nausea]] and vomiting, and abdominal discomfort), from their enlarged kidneys.&lt;ref name=&quot;TP-150518-E08&quot;&gt;{{cite journal | vauthors = Alam A, Perrone RD | title = Management of ESRD in patients with autosomal dominant polycystic kidney disease | journal = Advances in Chronic Kidney Disease | volume = 17 | issue = 2 | pages = 164–172 | date = March 2010 | pmid = 20219619 | doi = 10.1053/j.ackd.2009.12.006 }}&lt;/ref&gt;&lt;ref name=&quot;TP-150518-E09&quot;&gt;{{cite journal | vauthors = Wagner MD, Prather JC, Barry JM | title = Selective, concurrent bilateral nephrectomies at renal transplantation for autosomal dominant polycystic kidney disease | journal = The Journal of Urology | volume = 177 | issue = 6 | pages = 2250–4; discussion 2254 | date = June 2007 | pmid = 17509331 | doi = 10.1016/j.juro.2007.01.146 }}&lt;/ref&gt;&lt;ref name=&quot;TP-150518-E13&quot;&gt;{{cite journal | vauthors = Cristea O, Yanko D, Felbel S, House A, Sener A, Luke PP | title = Maximal kidney length predicts need for native nephrectomy in ADPKD patients undergoing renal transplantation | journal = Canadian Urological Association Journal | volume = 8 | issue = 7–8 | pages = 278–282 | date = July 2014 | pmid = 25210553 | pmc = 4137014 | doi = 10.5489/cuaj.2128 }}&lt;/ref&gt; In such cases, [[nephrectomy]] can be required due to intractable symptoms or when in the course of preparing for [[kidney transplantation]], the native kidneys are found to impinge upon the [[true pelvis]] and preclude the placement of a donor [[allograft]].&lt;ref name=&quot;TP-150518-E09&quot; /&gt;&lt;ref name=&quot;TP-150518-E13&quot; /&gt;&lt;ref name=&quot;TP-150518-E10&quot;&gt;{{cite journal | vauthors = Fuller TF, Brennan TV, Feng S, Kang SM, Stock PG, Freise CE | title = End stage polycystic kidney disease: indications and timing of native nephrectomy relative to kidney transplantation | journal = The Journal of Urology | volume = 174 | issue = 6 | pages = 2284–2288 | date = December 2005 | pmid = 16280813 | doi = 10.1097/01.ju.0000181208.06507.aa | s2cid = 25363382 }}&lt;/ref&gt;&lt;ref name=&quot;TP-150518-E11&quot;&gt;{{cite journal | vauthors = Cohen D, Timsit MO, Chrétien Y, Thiounn N, Vassiliu V, Mamzer MF, Legendre C, Méjean A | display-authors = 6 | title = [Place of nephrectomy in patients with autosomal dominant polycystic kidney disease waiting for renal transplantation] | journal = Progres en Urologie | volume = 18 | issue = 10 | pages = 642–649 | date = November 2008 | pmid = 18971106 | doi = 10.1016/j.purol.2008.06.004 }}&lt;/ref&gt; Additionally, native nephrectomy may be undertaken in the presence of suspected malignancy, as renal cell carcinoma (RCC) is two to three times more likely in the ADPKD population in [[Kidney failure|end-stage kidney disease]] (ESKD) than in the ESKD patients without ADPKD.&lt;ref name=&quot;TP-150518-E13&quot; /&gt;&lt;ref name=&quot;TP-150518-E12&quot;&gt;{{cite journal | vauthors = Hajj P, Ferlicot S, Massoud W, Awad A, Hammoudi Y, Charpentier B, Durrbach A, Droupy S, Benoît G | display-authors = 6 | title = Prevalence of renal cell carcinoma in patients with autosomal dominant polycystic kidney disease and chronic renal failure | journal = Urology | volume = 74 | issue = 3 | pages = 631–634 | date = September 2009 | pmid = 19616833 | doi = 10.1016/j.urology.2009.02.078 }}&lt;/ref&gt; Although the indications for nephrectomy in ADPKD may be related to kidney size, the decision to proceed with native nephrectomy is often undertaken on an individual basis, without specific reference to kidney size measurements.&lt;ref name=&quot;TP-150518-E13&quot; /&gt;

===Dialysis===
Two modalities of [[Kidney dialysis|dialysis]] can be used in the treatment of ADPKD patients: [[peritoneal dialysis]] and [[hemodialysis]].&lt;ref name=&quot;TP-150518-E14&quot;&gt;{{cite journal | vauthors = Courivaud C, Roubiou C, Delabrousse E, Bresson-Vautrin C, Chalopin JM, Ducloux D | title = Polycystic kidney size and outcomes on peritoneal dialysis: comparison with haemodialysis | journal = Clinical Kidney Journal | volume = 7 | issue = 2 | pages = 138–143 | date = April 2014 | pmid = 25852862 | pmc = 4377775 | doi = 10.1093/ckj/sft171 }}&lt;/ref&gt; Epidemiological data shows that ADPKD affects 5–13.4% of patients undergoing hemodialysis in Europe and in the United States,&lt;ref name=&quot;TP-150518-E15&quot;&gt;{{cite journal | vauthors = Nunes AC, Milani V, Porsch DB, Rossato LB, Mattos CB, Roisenberg I, Barros EJ | title = Frequency and clinical profile of patients with polycystic kidney disease in southern Brazil | journal = Renal Failure | volume = 30 | issue = 2 | pages = 169–173 | year = 2008 | pmid = 18300116 | doi = 10.1080/08860220701810265 | doi-access = free }}&lt;/ref&gt;&lt;ref name=&quot;TP-150518-E16&quot;&gt;{{cite journal | vauthors = Bleyer AJ, Hart TC | title = Polycystic kidney disease | journal = The New England Journal of Medicine | volume = 350 | issue = 25 | pages = 2622; author reply 2622 | date = June 2004 | pmid = 15201424 | doi = 10.1056/NEJM200406173502519 }}&lt;/ref&gt;&lt;ref name=&quot;TP-150518-E17&quot;&gt;{{cite journal | vauthors = Corradi V, Gastaldon F, Virzì GM, de Cal M, Soni S, Chionh C, Cruz DN, Clementi M, Ronco C | display-authors = 6 | title = Clinical pattern of adult polycystic kidney disease in a northeastern region of Italy | journal = Clinical Nephrology | volume = 72 | issue = 4 | pages = 259–267 | date = October 2009 | pmid = 19825331 | doi = 10.5414/CNP72259 }}&lt;/ref&gt; and about 3% in Japan.&lt;ref name=&quot;TP-150518-E18&quot;/&gt; Peritoneal dialysis has usually been contra-indicated in ADPKD patients with large kidney and liver volumes, due to expected physical difficulties in the procedure and possible complications;&lt;ref name=&quot;TP-150518-E14&quot; /&gt;&lt;ref name=&quot;TP-150518-E19&quot;&gt;{{cite journal | vauthors = Hamanoue S, Hoshino J, Suwabe T, Marui Y, Ueno T, Kikuchi K, Hazue R, Mise K, Kawada M, Imafuku A, Hayami N, Sumida K, Hiramatsu R, Hasegawa E, Sawa N, Takaichi K, Ubara Y | display-authors = 6 | title = Peritoneal Dialysis is Limited by Kidney and Liver Volume in Autosomal Dominant Polycystic Kidney Disease | journal = Therapeutic Apheresis and Dialysis | volume = 19 | issue = 3 | pages = 207–211 | date = June 2015 | pmid = 25612237 | doi = 10.1111/1744-9987.12272 | s2cid = 27836789 }}&lt;/ref&gt; however, no difference is seen in long-term morbidity between hemodialysis and peritoneal dialysis in ADPKD.&lt;ref name=&quot;TP-150518-E14&quot; /&gt;

===Kidney transplant===
Kidney transplantation is accepted as the preferred treatment for ADPKD patients with ESRD.&lt;ref name=&quot;TP-150518-E20&quot; /&gt; Among American patients on the kidney-transplant waiting list (as of December 2011), 7256 (8.4%) were listed due to cystic kidney disease and of the 16,055 renal transplants performed in 2011, 2057 (12.8%) were done for patients with cystic kidney disease, with 1,189 from deceased donors and 868 from living donors.&lt;ref name=&quot;TP-150518-E21&quot;&gt;{{cite journal | vauthors = Matas AJ, Smith JM, Skeans MA, Lamb KE, Gustafson SK, Samana CJ, Stewart DE, Snyder JJ, Israni AK, Kasiske BL | display-authors = 6 | title = OPTN/SRTR 2011 Annual Data Report: kidney | journal = American Journal of Transplantation | volume = 13 | issue = Suppl 1 | pages = 11–46 | date = January 2013 | pmid = 23237695 | pmc = 5527691 | doi = 10.1111/ajt.12019 }}&lt;/ref&gt;

=== Novel Therapies ===
There are several novel therapies currently underway aimed at slowing the progression of disease in APKD. Alternative therapeutic options include water therapy, the use of lipid-lowering agents, antiproliferative analogues, and synthetic peptides.&lt;ref name=&quot;:2&quot; /&gt;

Water Therapy

Increased water intake downregulates vasopressin activity. As a result, water therapy has been explored as a potential therapeutic intervention for individuals with ADPKD; however, studies examining its role in ADPKD advancement remain unclear.&lt;ref name=&quot;:2&quot; /&gt;

HMG-CoA reductase inhibitors

The progression of ADPKD leads to a decline in kidney function, with a marked decrease in glomerular filtration rate. As a result, treatment with statins is recommended by current guidelines for managing chronic kidney disease. The effect of statins on slowing ADPKD is inconclusive, with some trials showing a decrease in total kidney volume, while others showed no benefit on either total kidney volume or glomerular filtration rate.&lt;ref name=&quot;:2&quot; /&gt;

Somatostatin analogs

Somatostatin is are artificial peptide designed to mimic the function of an endogenous hormone that has many regulatory functions within the body, including restraining cell proliferation. Small phase 2 studies have shown that somatostatin analogues are effective at reducing the rate of total kidney volume growth and preserving glomerular filtration rate.&lt;ref name=&quot;:2&quot; /&gt; The use of somatostatin analogues may be restricted due to their side effects, which commonly include gastrointestinal issues such as diarrhea, abdominal discomfort, and gas, as well as conditions like gallstones and elevated blood sugar. 

Anti-proliferative agents

Proliferation of epithelial cells lining the cyst results in cyst expansion and contributes to disease progression. As a result of this mechanism, antiproliferative agents such as tyrosine kinase inhibitor bosutinib. However, results in clinical trials have shown mixed results, with studies showing a decrease in total kidney volume. &lt;ref name=&quot;:2&quot; /&gt;&lt;ref&gt;{{Cite journal |last1=Zhou |first1=Julie Xia |last2=Torres |first2=Vicente E. |date=May 2023 |title=Autosomal Dominant Polycystic Kidney Disease Therapies on the Horizon |url=https://linkinghub.elsevier.com/retrieve/pii/S2949813923000034 |journal=Advances in Kidney Disease and Health |language=en |volume=30 |issue=3 |pages=245–260 |doi=10.1053/j.akdh.2023.01.003|url-access=subscription }}&lt;/ref&gt;

==Prognosis==
In ADPKD patients, gradual cyst development and expansion result in kidney enlargement, and during the disease, [[glomerular filtration rate]] remains normal for decades before [[kidney function]] starts to progressively deteriorate, making early prediction of renal outcome difficult.&lt;ref name=&quot;TP-150519-E38&quot;&gt;{{cite journal | vauthors = Cornec-Le Gall E, Le Meur Y | title = Polycystic kidney disease: Kidney volume--a crystal ball for ADPKD prognosis? | journal = Nature Reviews. Nephrology | volume = 10 | issue = 9 | pages = 485–486 | date = September 2014 | pmid = 25092148 | doi = 10.1038/nrneph.2014.132 | s2cid = 22042874 }}&lt;/ref&gt; The CRISP study,&lt;ref name=&quot;TP-150515-017&quot; /&gt;&lt;ref name=&quot;TP-150519-E39&quot;/&gt; mentioned in the '''treatment''' section above, contributed to build a strong rationale supporting the prognostic value of total kidney volume (TKV) in ADPKD; TKV (evaluated by [[MRI]]) increases steadily and a higher rate of kidney enlargement correlated with accelerated decline of GFR, while patient height-adjusted TKV (HtTKV) ≥600 ml/m predicts the development of stage 3 chronic kidney disease within 8 years.&lt;ref name=&quot;TP-150519-E38&quot; /&gt;

Besides TKV and HtTKV, the [[glomerular filtration rate|estimated glomerular filtration rate]] (eGFR) has also been tentatively used to predict the progression of ADPKD.&lt;ref name=&quot;TP-150519-E38&quot; /&gt; After the analysis of CT or MRI scans of 590 patients with ADPKD treated at the [[Mayo Clinic|Mayo Translational Polycystic Kidney Disease Center]], Irazabal and colleagues developed an imaging-based classification system to predict the rate of eGFR decline in patients with ADPKD.&lt;ref name=&quot;TP-150519-E38&quot; /&gt;&lt;ref name=&quot;TP-150519-E39&quot;/&gt; In this prognostic method, patients are divided into five subclasses of estimated kidney growth rates according to age-specific HtTKV ranges (1A, &lt;1.5%; 1B, 1.5–3.0%; 1C, 3.0–4.5%; 1D, 4.5–6.0%; and 1E, &gt;6.0%) as delineated in the CRISP study.&lt;ref name=&quot;TP-150519-E38&quot; /&gt;&lt;ref name=&quot;TP-150519-E39&quot; /&gt; The decline in eGFR over the years following initial TKV measurement is significantly different between all five patient subclasses, with those in subclass 1E having the most rapid decline.&lt;ref name=&quot;TP-150519-E38&quot; /&gt; Some of the most common causes of death in patients with ADPKD are various infections (25%), a ruptured berry aneurysm (15%), or coronary/hypertensive heart disease (40%).&lt;ref&gt;{{cite book | vauthors = Kumar V, Abbas AK, Aster JC |title=Robbins and Cotran Pathologic Basis of Disease |date=2015 |location=Philadelphia, PA |isbn=978-1-4557-2613-4 |edition=Ninth |pages=947|oclc=879416939 }}&lt;/ref&gt;

== References ==
{{Reflist}}

== External links ==
* {{cite web | title = Polycystic Kidney Disease | url = http://kidney.niddk.nih.gov/kudiseases/pubs/polycystic/index.htm | work = National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | publisher = U.S. Department of Health and Human Services | archive-url = https://web.archive.org/web/20110608142128/http://kidney.niddk.nih.gov/kudiseases/pubs/polycystic/index.htm | archive-date = 2011-06-08 }}
* {{cite book | chapter = Polycystic Kidney Disease | title = Genes and Disease [Internet]. | year = 1998 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK22209/ | publisher = National Center for Biotechnology Information (US) | location = Bethesda (MD) }}
{{Medical resources
| ICD11           = {{ICD11|GB81}}
| ICD10           = {{ICD10|Q61}}
| ICD9            = {{ICD9|753.1}}
| ICDO            =
| OMIM            = 601313
| OMIM_mult       = {{OMIM|173910||none}}
| MedlinePlus     = 000502
| eMedicineSubj   = radio
| eMedicineTopic  = 68
| DiseasesDB      = 10262
| MeshID          = D016891
| Orphanet        = 730
}}
{{commons category|Autosomal dominant polycystic kidney disease}}

{{Congenital malformations of urinary system}}
{{Cystic diseases}}

{{DEFAULTSORT:Autosomal Dominant Polycystic Kidney}}
[[Category:Kidney diseases]]
[[Category:Cat diseases]]
[[Category:Channelopathies]]
[[Category:Rare diseases]]
[[Category:Autosomal dominant disorders]]