*Polycystic Kidney Disease

Chapter: Polycystic Kidney Disease
McMaster Section Editor(s): Christine M. Ribic, Karen C.Y. To
Section Editor(s) in Interna Szczeklika: Franciszek Kokot, Robert Drabczyk
McMaster Author(s): Alistair J. Ingram
Author(s) in Interna Szczeklika: Michał Nowicki, Robert Drabczyk
Additional Information

Definition, Etiology, PathogenesisTop

Polycystic kidney disease (PKD) is an inherited condition associated with presence of multiple cysts in the renal cortex and medulla. Autosomal dominant PKD (ADPKD) develops in adults and is the most frequent genetic kidney disease (1/400-1000 births). It accounts for 8% to 15% of cases of end-stage renal failure requiring renal replacement therapy. About 85% of clinically affected individuals have a mutation in the PKD-1 gene on chromosome 16, which encodes for the ciliary protein polycystin-1, whilst 15% have mutations in PKD-2 on chromosome 4, coding for the ciliary calcium channel protein polycystin-2. Families with mutations in PKD-1 tend to be more severely affected and are therefore more likely to come to clinical attention. Autosomal recessive PKD (ARPKD) has a prevalence rate of approximately 1 in 20,000 births and is diagnosed in infancy (some cases are detected in utero).

PKD may remain asymptomatic for many years and is often detected incidentally in the course of abdominal imaging performed for unrelated indications. The presenting symptom of PKD may be hypertension or other complications of CKD, depending on glomerular filtration rate (GFR) (see Chronic Kidney Disease). Typical renal manifestations are flank pain and hematuria, often caused by cyst rupture. Approximately 20% of patients develop kidney stones. In some individuals extrarenal lesions are also observed, including hepatic cysts (affecting ~60% of patients; very rarely symptomatic), intracranial aneurysms (affecting 4%-8% of patients with asymptomatic PKD; the cause of ~10% of deaths in patients with PKD), and pancreatic cysts (almost always asymptomatic).

Diagnosis Top

Diagnosis is based on imaging studies, mainly ultrasonography, which may reveal numerous renal cysts and markedly enlarged kidneys. Genetic testing is not performed routinely. Ultrasound diagnostic criteria for ADPKD have been formulated for those with a family history of PKD, including those with unknown genotype and those from known type I families:Evidence 1High Quality of Evidence (high confidence that we know true effects of intervention). Pei Y, Obaji J, Dupuis A, et al. Unified criteria for ultrasonographic diagnosis of ADPKD. J Am Soc Nephrol. 2009 Jan;20(1):205-12. doi: 10.1681/ASN.2008050507. Epub 2008 Oct 22. PubMed PMID: 18945943; PubMed Central PMCID: PMC2615723.

1) In individuals at risk but with unknown genotype:

a) 15 to 39 years of age, at least 3 unilateral or bilateral kidney cysts.

b) 40 to 59 years of age, at least 2 cysts in each kidney.

c) 60 years or older, at least 4 cysts in each kidney.

2) In individuals from a known type I PKD family:Evidence 2Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to the relatively low number of observations (imprecision). Ravine D, Gibson RN, Walker RG, Sheffield LJ, Kincaid-Smith P, Danks DM. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1. Lancet. 1994 Apr 2;343(8901):824-7. PubMed PMID: 7908078.

a) <30 years of age, ≥2 cysts in one or both kidneys.

b) 30 to 59 years of age, ≥2 cysts in each kidney.

c) ≥60 years of age, ≥4 cysts in each kidney.

In families with a known PKD-2 mutation, ultrasound criteria are less sensitive and genetic testing may be preferred. Differential diagnosis most frequently includes multiple simple cysts. PKD is suggested by a positive family history and the presence of extrarenal lesions. Unfortunately, without family history there is not a definitive number of cysts that can establish the diagnosis of ADPKD. As genetic testing becomes more widely available, it is probable that this will change.

Treatment Top

Treatment is symptomatic and supportive, as in CKD. Normalizing the blood pressure is of vital importance, generally with a single renin-angiotensin-aldosterone (RAA) system inhibitor. Dual RAA system blockade provides no additive benefit,Evidence 3For using a single RAA inhibitor and for aiming at lower BP among those with GFR >60: Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). For not using double RAA blockade: Strong recommendation (downsides clearly outweigh benefits; right action for all or almost all patients). For both: High Quality of Evidence (high confidence that we know true effects of the intervention; we did not lower QoE for indirectness). Torres VE, Abebe KZ, Chapman AB, et al; HALT-PKD Trial Investigators. Angiotensin blockade in late autosomal dominant polycystic kidney disease. N Engl J Med. 2014 Dec 11;371(24):2267-76. doi: 10.1056/NEJMoa1402686. Epub 2014 Nov 15. PubMed PMID: 25399731; PubMed Central PMCID: PMC4284824. Schrier RW, Abebe KZ, Perrone RD, et al; HALT-PKD Trial Investigators. Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med. 2014 Dec 11;371(24):2255-66. doi: 10.1056/NEJMoa1402685. Epub 2014 Nov 15. PubMed PMID: 25399733; PubMed Central PMCID: PMC4343258.  whilst a lower blood pressure target (<110/75 mm Hg) may be of benefit in those with a GFR >60 mL/min/1.73 m2,Evidence 4For using a single RAA inhibitor and for aiming at lower BP among those with GFR >60: Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). For not using double RAA blockade: Strong recommendation (downsides clearly outweigh benefits; right action for all or almost all patients). For both: High Quality of Evidence (high confidence that we know true effects of the intervention; we did not lower QoE for indirectness). Torres VE, Abebe KZ, Chapman AB, et al; HALT-PKD Trial Investigators. Angiotensin blockade in late autosomal dominant polycystic kidney disease. N Engl J Med. 2014 Dec 11;371(24):2267-76. doi: 10.1056/NEJMoa1402686. Epub 2014 Nov 15. PubMed PMID: 25399731; PubMed Central PMCID: PMC4284824. Schrier RW, Abebe KZ, Perrone RD, et al; HALT-PKD Trial Investigators. Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med. 2014 Dec 11;371(24):2255-66. doi: 10.1056/NEJMoa1402685. Epub 2014 Nov 15. PubMed PMID: 25399733; PubMed Central PMCID: PMC4343258.  although hard outcome data is lacking. Maintenance of a high fluid (water) intake to suppress antidiuretic hormone may be of benefit in slowing disease progression; it is certainly unlikely to be harmful.Evidence 5Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of evidence lowered due to indirectness to patient-important outcomes. Barash I, Ponda MP, Goldfarb DS, Skolnik EY. A pilot clinical study to evaluate changes in urine osmolality and urine cAMP in response to acute and chronic water loading in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2010 Apr;5(4):693-7. doi: 10.2215/CJN.04180609. Epub 2010 Feb 18. PubMed PMID: 20167686; PubMed Central PMCID: PMC2849694. Some other therapies to slow progression should probably not be offered at this time, as they are associated with questionable benefit, high toxicity (sirolimus and everolimus),Evidence 6Strong recommendation (downsides clearly outweigh benefits; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Serra AL, Poster D, Kistler AD, et al. Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med. 2010 Aug 26;363(9):820-9. doi: 10.1056/NEJMoa0907419. Epub 2010 Jun 26. PubMed PMID: 20581391. Walz G, Budde K, Mannaa M, et al. Everolimus in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2010 Aug 26;363(9):830-40. doi: 10.1056/NEJMoa1003491. Epub 2010 Jun 26. Erratum in: N Engl J Med. 2010 Sep 16;363(12):1190. N Engl J Med. 2010 Nov 11;363(20):1977. PubMed PMID: 20581392. or both, or a very high cost (tolvaptan).Evidence 7Weak recommendation (downsides, to a major degree, likely outweigh benefits, but the balance is close or uncertain; an alternative course of action may be better for some patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Quality of Evidence was not lowered due to indirectness to unknown long-term effects. Note: The direction of recommendation was due to both side effects as well as a very high cost measured as of 2015 in hundreds of thousands of dollars per year. Torres VE, Chapman AB, Devuyst O, et al; TEMPO 3:4 Trial Investigators. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012 Dec 20;367(25):2407-18. doi: 10.1056/NEJMoa1205511. Epub 2012 Nov 3. PubMed PMID: 23121377; PubMed Central PMCID: PMC3760207.  Episodes of hematuria are treated symptomatically. Patients with PKD and end-stage renal failure are good candidates for kidney transplantation due to the nonimmune nature of the disease.

We would love to hear from you

  • Do you have any comments?
  • Have you found a mistake?
  • Would you like to suggest a feature?

We use cookies to ensure you get the best browsing experience on our website. Refer to our Cookies Information and Privacy Policy for more details.