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AnneLumiaho

Polycystic Kidney Disease

Essentials

  • In autosomal dominant polycystic kidney disease (ADPKD), bilateral cysts and kidney size increase with age.
  • About 50% of patients develop end-stage renal failure by the age of 60.
  • Patients with ADPKD may also have cerebrovascular aneurysms, liver cysts and valvular heart disease at a young age, already, or even in childhood, and/or hypertension, i.e. it is a systemic disease.
  • Family history is important and ultrasonography is diagnostic.
  • The prognosis of the disease can be assessed by measuring the size of the kidneys by MRI.

Polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD)

  • Inherited as an autosomal dominant trait, meaning that the children of a patient have a 50% risk of inheriting the disease.
  • The prevalence of ADPKD varies between 1 and 5 per 10 000. In Europe, its prevalence is estimated to be 1/2 500 http://www.orpha.net/en/disease/detail/730.
  • Cysts develop in both kidneys, increasing and growing with age. The kidneys become larger (sometimes weighing up to several kilograms), and renal failure develops.
  • About 70% of patients require renal dialysis by the age of 40 to 70 years.
  • The disease is usually caused by a gene defect in either the PKD1 or the PKD2 gene. Mutations causing the disease have been described in several other genes as well but these are rare.
  • In 10-20% of patients there is no positive family history but the disease is caused by a new spontaneous mutation.
    • A mutation in the PKD2 gene causes a clearly milder disease with dialysis required at an average age of 69 years, whereas patients with PKD1 disease often need dialysis at an average age of 53 years, already.
    • About 80% of patients with polycystic disease have PKD1 disease.
  • Most common initial symptoms
    • Abdominal pain
    • Haematuria
    • Hypertension
  • Diagnosis by ultrasonography
    • Besides a family history of polycystic kidney disease, the diagnosis requires at least 3 cysts in each kidney in patients from 15 to 39 years of age or at least 2 cysts in each kidney in patients from 40 to 59 years of age.
    • MRI and contrast enhanced CT are somewhat more sensitive than ultrasonography in excluding the disease.
    • If there is no disease in the family or the clinical picture is atypical, a gene test can be performed for confirmation.
  • The risk of cerebrovascular aneurysms is significantly increased in patients who have a relative with earlier stroke or diagnosed aneurysm.
    • These patients should undergo cerebrovascular MRI and, if the findings are normal, the examination should be repeated every 5 to 10 years depending on other risk factors.
  • Liver cysts are very common. They develop at an earlier age in female than in male patients. If liver cysts are found, the finding supports the diagnosis of ADPKD.
    • The liver may become enlarged but its function usually remains normal.
    • Oestrogen has been found to increase the growth of liver cysts.
  • Patients have an increased risk of valvular heart disease, particularly mitral regurgitation, mitral prolapse or aortic valve regurgitation, and of aortic dissection.
  • Colonic diverticula and hernias and pancreatic ranulas are more common in patients with ADPKD.
  • Cysts may be associated with pain caused by stretching of the fibrous capsule of the kidney. A cyst may rupture causing acute pain and haematuria. A cyst may also become infected.
  • Hypertension is found in as many as 35% of children with the disease.
  • Factors worsening the prognosis of kidney disease include
    • hypertension before the age of 35 years
    • cyst ruptures / haematuria before the age of 35 years
    • male sex
    • mutation in the PKD1 gene
    • GFR decreased at an early stage
    • large size of kidneys.
  • The size of the kidneys can best be measured by MRI. The size can be used to assess the prognosis of the disease (Mayo classification).
  • Treatment
  • If parents so wish, children can be investigated by ultrasonography. Gene testing is also possible. If parents do not want diagnostic examinations for their children, at least blood pressure should be monitored every 3 years from the age of 5 years on and urine should be monitored for the possible development of proteinuria.
    • In children, even one renal cyst is diagnostic.
    • Not detecting any cysts does not exclude ADPKD. In that case, gene testing can be considered.

Autosomal recessive polycystic kidney disease, ARPKD (infantile form)

  • Prevalence 1:10 000-1:40 000
  • Most cases are due to mutations in the PKHD1 gene. Mutations associated with the disease have also been described in other genes. The diagnosis can be confirmed by a gene test.
  • In the severe form of the disease, which is usually detected early, mortality is still high even today; an affected neonate will have very large kidneys and pulmonary hypoplasia.
  • The disease is detected before the age of 1 year, at the age of 1-20 years, and after the age of 20 in one out of three cases, respectively.
  • Most severe cases of ARPKD are discovered towards the end of pregnancy or at birth, but they may be discovered by ultrasonography as early as in the second or third trimester.
    • Liver disease is usually not discovered during pregnancy.
  • Disease of the liver and the kidneys
    • Liver disease may dominate the clinical picture.
      • Hepatic fibrosis leads to portal hypertension, splenomegaly and oesophageal varices.
      • Liver cysts
      • Enlarged liver and bile ducts
  • In 50% of patients, renal failure requiring dialysis develops within the first year of life.
  • The typical finding in ultrasonography is enlarged kidneys. In severe disease, the kidneys may fill the abdominal cavity after birth and be palpable.
  • Only a few patients cope without dialysis until the age of 40 to 50 years.
  • About half of the patients require renal transplantation before the age of 10 years.
  • 75% of patients have hypertension.
  • There is no specific treatment available. Expertise from various specialties is needed to treat pulmonary hypoplasia, hypertension, chronic renal failure and hepatic complications. Some patients require both hepatic and renal transplantation.
  • The family should be offered genetic counselling.
  • See further information in Orphanet ORPHA731 http://www.orpha.net/en/disease/detail/731

    References

    • Chebib FT, Perrone RD, Chapman AB, et al. A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan. J Am Soc Nephrol 2018;29(10):2458-2470 [PubMed]
    • Wicher D, Obrycki Ł, Jankowska I. Autosomal Recessive Polycystic Kidney Disease-The Clinical Aspects and Diagnostic Challenges. J Pediatr Genet 2021;10(1):1-8 [PubMed]
    • Cornec-Le Gall E, Alam A, Perrone RD. Autosomal dominant polycystic kidney disease. Lancet 2019;393(10174):919-935 [PubMed]
    • Chapman AB, Devuyst O, Eckardt KU, et al. Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2015;88(1):17-27 [PubMed]