| Polycystic kidney disease |
| Classification and external resources |
Polycystic kidneys |
| ICD-10 |
Q61 |
| ICD-9 |
753.1 |
| OMIM |
173900 |
| DiseasesDB |
10262 10280 |
| MedlinePlus |
000502 |
| eMedicine |
med/1862 ped/1846 radio/68 radio/69 |
| MeSH |
D007690 |
Polycystic kidney disease (PKD or PCKD, also known as polycystic kidney syndrome) is a cystic genetic disorder of the kidneys.[1] There are two types of PKD: autosomal dominant polycystic kidney disease (ADPKD) and the less-common autosomal recessive polycystic kidney disease (ARPKD).
It occurs in humans and some other animals. PKD is characterized by the presence of multiple cysts (hence, "polycystic") typically in both kidneys; however 17% of cases initially present with observable disease in one kidney, with most cases progressing to bilateral disease in adulthood.[2] The cysts are numerous and are fluid-filled, resulting in massive enlargement of the kidneys. The disease can also damage the liver, pancreas and, in some rare cases, the heart and brain. The two major forms of polycystic kidney disease are distinguished by their patterns of inheritance.
Polycystic kidney disease is one of the most common life-threatening genetic diseases, affecting an estimated 12.5 million people worldwide.[3]
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Contents
- 1 Types
- 1.1 Autosomal dominant
- 1.2 Autosomal recessive
- 2 Extrarenal manifestations
- 3 Clinical trials and possible future treatments
- 4 References
- 5 External links
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Types
Autosomal dominant
CT scan showing autosomal dominant polycystic kidney disease
Autosomal dominant polycystic kidney disease (ADPKD) is the most common of all the hereditary cystic kidney diseases[2][4][5] with an incidence of 1 to 2:1,000 live births.[2][5] Studies show that 10% of end-stage renal disease (ESRD) patients being treated with hemodialysis in Europe and the U.S. were initially diagnosed and treated for ADPKD.[2] ADPKD does not appear to demonstrate a preference for any particular ethnicity.
ADPKD is characterized by progressive cyst development and bilaterally enlarged kidneys with multiple cysts. There are three genetic mutations in the PKD-1, PKD-2, and PKD3 gene with similar phenotypical presentations. Gene PKD-1 is located on chromosome 16 and codes for a protein involved in regulation of cell cycle and intracellular calcium transport in epithelial cells, and is responsible for 85% of the cases of ADPKD. A group of voltage-linked calcium channels are coded for by PKD-2 on chromosome 4. PKD3 recently appeared in research papers as a postulated 3rd gene. At this time, PKD3 has not been proven.[2][4] Fewer than 10% of cases of ADPKD appear in non-ADPKD families.
Cyst formation begins in utero from any point along the nephron, although fewer than 5% of nephrons are thought to be involved. As the cysts accumulate fluid, they enlarge, separate entirely from the nephron, compress the neighboring renal parenchyma, and progressively compromise renal function.
Under the function of gene defect, epithelial cells of renal tubule turn into epithelial cells of cyst wall after phenotype change, and begin to have the function of secreting cyst fluid, which leads to continuous cysts enlargement.[6]
Autosomal recessive
Studies show that the incidence of ARPKD (OMIM #263200) is 1:20,000 live births and is typically identified in the first few weeks after birth. Unfortunately, resulting hypoplasia results in a 30% death rate in neonates with ARPKD.[2] In ARPKD kidneys retain their shape but are larger than the normal anatomical range with dilated collecting ducts from the medulla to the cortex.
The major extrarenal complications of ADPKD include cerebral aneurysms, hepatic cysts, pancreatic cysts, cardiac valve disease (especially mitral valve prolapse), colonic diverticula, and aortic root dilatation.
Clinical trials and possible future treatments
It is known that a certain molecule known as cAMP is involved in the enlargement of kidney cysts in PKD kidneys.[7] Various studies on rodents have shown that a molecule, called vasopressin, increases levels of cAMP in the body. When mice with PKD were given a chemical that blocks vasopressin, there was an impressive decrease in kidney size and some preservation of kidney function. Similarly, when studied mice consumed excessive amounts of water (which decreases levels of vasopressin), a similar result was seen. It has therefore been suggested that consuming large amounts of water may possibly assist in the treatment of early stage PKD.[8][9]
As humans do not always mimic rodents in clinical trials, it is currently not yet certain whether vasopressin inhibitors, such as water, will have corresponding results in humans, or what negative effects excessive water intake may have on the kidneys of individuals with PKD. Clinical trials are currently underway in this field.[10]
It has also been suggested that treatment with medications inhibiting vasopressin may assist in the management of PKD and reduce the speed at which kidney cysts form and grow, delaying the onset of end stage renal failure. Clinical trials are currently underway in the testing of Tolvaptan, a U.S. Food and Drug Administration (FDA) approved medication which has not yet been approved for use in the treatment of PKD.[11]
References
- ^ "polycystic kidney disease" at Dorland's Medical Dictionary
- ^ a b c d e f Bisceglia, M; et al (2006). "Renal cystic diseases: a review". Advanced Anatomic Pathology (13): 26–56.
- ^ Wilson PD. Polycystic kidney disease. N Engl J Med 2004;350:151-164
- ^ a b Torres, WE; Harris PC, Pirson Y (2007). "Autosomal dominant polycystic urology". Lancet 369 (9569): 1287–301. doi:10.1016/S0140-6736(07)60601-1.
- ^ a b Simons, M; Walz G (2006). "Polycystic kidney disease: cell division with a c(l)ue?". Kidney International (70): 854–864.
- ^ 梅长林，常染色体显性多囊肾病，肾脏病学，第三版，人民卫生出版社|year=2008,9|pages=1746
- ^ "cAMP Regulates Cell Proliferation and Cyst Formation in Autosomal Polycystic Kidney Disease Cells". Jasn.asnjournals.org. 2000-07-01. http://jasn.asnjournals.org/content/11/7/1179.abstract. Retrieved 2012-02-16.
- ^ http://www.pkdcharity.co.uk/PKD%20Charity%20Newsletter%20Spring%202008.pdf
- ^ http://cjasn.asnjournals.org/content/4/6/1140.full.pdf
- ^ "High Water Intake to Slow Progression of Polycystic Kidney Disease - Full Text View". ClinicalTrials.gov. http://clinicaltrials.gov/ct2/show/NCT00784030. Retrieved 2012-02-16.
- ^ "Otsuka Maryland Research Institute, Inc. Granted Fast Track Designation For Tolvaptan In PKD". Medicalnewstoday.com. http://www.medicalnewstoday.com/releases/38392.php. Retrieved 2012-02-16.
External links
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Congenital malformations and deformations of urinary system (Q60–Q64, 753)
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| Abdominal |
| Kidney |
- Renal agenesis/Potter sequence, Papillorenal syndrome
- cystic
- Polycystic kidney disease
- Meckel syndrome
- Multicystic dysplastic kidney
- Medullary sponge kidney
- Horseshoe kidney
- Renal ectopia
- Nephronophthisis
- Dent's disease
- Alport syndrome
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| Ureter |
- Ectopic ureter
- Megaureter
- Duplicated ureter
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| Pelvic |
| Bladder |
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| Urethra |
- Epispadias
- Hypospadias
- Posterior urethral valves
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| Vestigial |
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noco/acba/cong/tumr, sysi/epon, urte
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proc/itvp, drug (G4B), blte, urte
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Health science - Medicine - Cystic diseases
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| Respiratory system |
- Langerhans cell histiocytosis
- Lymphangiomyomatosis
- Cystic bronchiectasis
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| Skin |
- stratified squamous: follicular infundibulum
- Epidermoid cyst/Proliferating epidermoid cyst
- Milia
- Eruptive vellus hair cyst
- outer root sheath
- Trichilemmal cyst/Pilar cyst/Proliferating trichilemmal cyst/Malignant trichilemmal cyst
- sebacious duct
- Steatocystoma multiplex/Steatocystoma simplex
- Keratocyst
- nonstratified squamous: Cutaneous ciliated cyst
- Hidrocystoma
- no epithelium: Pseudocyst of the auricle
- Mucocele
- other/ungrouped: Cutaneous columnar cyst
- Keratin implantation cyst
- Verrucous cyst
- Adenoid cystic carcinoma
- Breast cyst
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| Musculoskeletal system |
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| Digestive system |
- liver: Polycystic liver disease
- Congenital hepatic fibrosis
- Peliosis hepatis
- bile duct: Biliary hamartomas
- Caroli disease
- Choledochal cysts
- Bile duct hamartoma
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| Nervous system |
- Cystic leukoencephalopathy
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| Genitourinary system |
- Polycystic kidney disease
- Autosomal dominant polycystic kidney
- Autosomal recessive polycystic kidney
- Medullary cystic kidney disease
- Congenital cystic dysplasia
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| Other conditions |
- Hydatid cyst
- Von Hippel-Lindau syndrome
- Tuberous sclerosis
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死因は心臓による物が最多である：心臓病(36%)、感染症(24%)、神経学的なイベント(12%)。剖検では心肥大が89%の患者に見られ、冠動脈疾患が81%に見られた。神経学的な死亡(neurologic deaths)では頭蓋内動脈瘤破裂が主であり(6%)、頭蓋内出血が5%であった。
