Polycystic kidney disease

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Polycystic kidney disease
Other namesKidney - polycystic[1]
Severely affected polycystic kidneys removed at time of transplantation
SpecialtyNephrology
SymptomsAbdominal pain[1]
TypesADPKD[2] and ARPKD[3]
Diagnostic methodMRI, CT scan, Ultrasound[1]
TreatmentAntihypertensives, Life style management[4]

Polycystic kidney disease (PKD or PCKD, also known as polycystic kidney syndrome) is a

renal tubules become structurally abnormal, resulting in the development and growth of multiple cysts within the kidney.[7] These cysts may begin to develop in utero, in infancy, in childhood, or in adulthood.[8]
Cysts are non-functioning tubules filled with fluid pumped into them, which range in size from microscopic to enormous, crushing adjacent normal tubules and eventually rendering them non-functional as well.

PKD is caused by abnormal genes that produce a specific abnormal protein; this protein has an adverse effect on tubule development. PKD is a general term for two types, each having their own pathology and genetic cause: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). The abnormal gene exists in all cells in the body; as a result, cysts may occur in the liver, seminal vesicles, and pancreas. This genetic defect can also cause aortic root aneurysms, and aneurysms in the circle of Willis cerebral arteries, which if they rupture, can cause a subarachnoid hemorrhage.

Diagnosis may be suspected from one, some, or all of the following: new onset flank pain or red urine; a positive family history; palpation of enlarged kidneys on physical exam; an incidental finding on abdominal

eGFR). Definitive diagnosis is made by abdominal CT
exam.

Complications include hypertension due to the activation of the

angiotensin receptor blockers (ARBs). Infections are treated with antibiotics. Declining renal function is treated with renal replacement therapy (RRT): dialysis and/or transplantation
. Management from the time of the suspected or definitive diagnosis is by an appropriately trained doctor.

Signs and symptoms

Signs and symptoms include high blood pressure, headaches, abdominal pain, blood in the urine, and excessive urination.[1] Other symptoms include pain in the back, and cyst formation (renal and other organs).[9]

Cause

PKD is caused by abnormal genes which produce a specific abnormal protein which has an adverse effect on tubule development. PKD is a general term for two types, each having their own pathology and genetic cause: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).[10][11]

Autosomal dominant

Main article: Autosomal dominant polycystic kidney disease
CT scan showing autosomal dominant polycystic kidney disease
Cartoon of autosomal dominant polycystic kidney disease with normal kidney inset to right of diagram
Cartoon of autosomal recessive polycystic kidney disease with normal kidney inset to right of diagram

end-stage kidney disease (ESKD) patients being treated with dialysis in Europe and the U.S. were initially diagnosed and treated for ADPKD.[12][11]

PKD2, and PKD3 have similar phenotypical presentations.[15]

Autosomal recessive

PKHD1 is involved.[12][11]

Mechanism

PKD1 and PKD2

Both autosomal dominant and autosomal recessive polycystic kidney disease cyst formation are tied to abnormal

polycystin-2 proteins appear to be involved in both autosomal dominant and recessive polycystic kidney disease due to defects in both proteins.[21] Both proteins have communication with calcium channel proteins, and causes reduction in resting (intracellular) calcium and endoplasmic reticulum storage of calcium.[22]

The disease is characterized by a ‘second hit’ phenomenon, in which a mutated dominant allele is inherited from a parent, with cyst formation occurring only after the normal, wild-type gene sustains a subsequent second genetic ‘hit’, resulting in renal tubular cyst formation and disease progression.[21]

PKD results from defects in the

primary cilium, an immotile, hair-like cellular organelle present on the surface of most cells in the body, anchored in the cell body by the basal body.[21] In the kidney, primary cilia have been found to be present on most cells of the nephron, projecting from the apical surface of the renal epithelium into the tubule lumen. The cilia were believed to bend in the urine flow, leading to changes in signalling, however this has since been shown to be an experimental error (the bending of cilia was an artifact of focal plane compensation, and also the actual effect on micturition by severe hypertension and cardiac arrest) and that bending of cilia does not contribute to alterations in Ca flux. While it is not known how defects in the primary cilium lead to cyst development, it is thought to possibly be related to disruption of one of the many signaling pathways regulated by the primary cilium, including intracellular calcium, Wnt/β-catenin, cyclic adenosine monophosphate (cAMP), or planar cell polarity (PCP). Function of the primary cilium is impaired, resulting in disruption of a number of intracellular signaling cascades which produce differentiation of cystic epithelium, increased cell division, increased apoptosis, and loss of resorptive capacity.[11][21]

Diagnosis

Polycystic kidney disease can be ascertained via a

heart murmurs and elevated blood pressure.[1]

Natural history

Most cases progress to bilateral disease in adulthood.[12]

Treatment

Chr 11 FISH-mapped BACs from CGAP

In 2018, Jynarque (Tolvaptan) was introduced [24] as the first FDA-approved treatment for PKD. In a recent long-term study, patients using Tolvaptan had a 6.4% higher kidney function after 5 years compared to standard of care.[25] In 2019, a team of researchers at UCSB found that a ketogenic diet might be able to halt, or even reverse progression in mice,[26] and the results of a first human case series study are showing potential benefit.[27] The results of a 3-month randomized, prospective dietary intervention clinical trial are pending.[28] In addition, recent research indicates that mild to moderate calorie restriction or time-restricted feeding [29] slow the progression of autosomal dominant polycystic kidney disease (ADPKD) in mice[30] [31] Patient communities have been combining both ketogenic diets

nephrologist or other practitioner and the patient will have to decide what form of renal replacement therapy will be used to treat end-stage kidney disease (kidney failure, typically stage 4 or 5 of chronic kidney disease).[35]

That will either be some form of dialysis, which can be done at least two different ways at varying frequencies and durations (whether it is done at home or in the clinic depends on the method used and the patient's stability and training) and eventually, if they are eligible because of the nature and severity of their condition and if a suitable match can be found, unilateral or bilateral kidney transplantation.[35]

A Cochrane Review study of autosomal dominant polycystic kidney disease made note of the fact that it is important at all times, while avoiding

bacteriocidal drugs".[11][35]

Prognosis

ADPKD individuals might have a normal life; conversely, ARPKD can cause kidney dysfunction and can lead to kidney failure by the age of 40–60. ADPKD1 and ADPKD2 are very different, in that ADPKD2 is much milder.[36]

Currently, there are no therapies proven effective to prevent the progression of ADPKD.[37]

Epidemiology

PKD is one of the most common hereditary diseases in the United States, affecting more than 600,000 people. It is the cause of nearly 10% of all end-stage renal disease. It equally affects men, women, and all races.[38] PKD occurs in some animals as well as humans.[39][40]

See also

References

  1. ^ a b c d e "Polycystic kidney disease". MedlinePlus Medical Encyclopedia. Retrieved 2015-07-30.
  2. ^ "Autosomal Dominant Polycystic Kidney Disease". National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Retrieved 3 January 2018.
  3. ^ "Autosomal Recessive Polycystic Kidney Disease". National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Retrieved 3 January 2018.
  4. ^ "What Is Polycystic Kidney Disease?". National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Retrieved 3 January 2018.
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  28. ^ Müller R (2022-08-23). "Ketogenic Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease (ADPKD)". University of Cologne.
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  32. ^ Spencer S (2021-12-25). "6 Ways People with PKD Can Lower Their Blood Pressure". Medium. Retrieved 2022-10-24.
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  34. ^ "Breakthrough Results After 7 Years of Reversing Pkd". 2022-10-20. Retrieved 2022-10-24.
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  36. ^ Torra R (2018-07-20). Talavera F, Aronoff GR (eds.). "Polycystic Kidney Disease: Practice Essentials, Background, Pathophysiology". Medscape.
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  39. ^ "Polycystic kidney disease (PKD): Gene test and negative register". International Cat Care. Archived from the original on 17 November 2016. Retrieved 2 November 2014.
  40. ^ "PKD - Polycystic Kidney Disease - British Shorthair". Antagene. Archived from the original on 17 August 2018. Retrieved 2 November 2014.

Further reading

External links

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