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Polycystic Kidney Disease

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Overview

Polycystic kidney disease (PKD) is an inherited disorder in which the renal tubules form cysts and become non-functional, which fill with fluid and exert pressure on adjacent normal tubules, damaging them. Cysts may also form in other areas, including the liver, pancreas, and spleen.

PKD can be divided into:

  • Autosomal dominant polycystic kidney disease (ADPKD) – subdivided into:
    • PKD1 – around 85% of cases with an abnormality on chromosome 16
      • Encodes for polycystin-1, symptoms are generally more severe
    • PKD2 – around 15% of cases with an abnormality on chromosome 4
      • Encodes for polycystin-2, symptoms are generally less severe
    • PKD3 – no gene locus has been identified yet
  • Autosomal recessive polycystic kidney disease (ARPKD)

This chapter will focus on ADPKD.

Epidemiology

  • ADPKD tends to present between the ages of 30-60 years
  • ARPKD tends to present from birth and may be prenatally diagnosed
  • ARPKD is much less common than ADPKD
  • ARPKD has a prevalence of around 10 per 100,000 births
  • PDK makes up for ~10% of people on dialysis
  • Prevalence in Europe is around 4 per 10,000

Presentation

ADPKD

Features include:

  • Haematuria
  • Polyuria
  • Loin pain – due to renal cysts or extra-renal cysts (e.g. hepatic cysts and enlargement)
  • Bilateral kidney enlargement – may be noticed on an abdominal examination
  • Hypertension
  • Recurrent urinary tract infections (UTIs)
  • Renal stones
  • Features of extra-renal manifestations:
    • Hepatomegaly due to liver cysts – most common
    • Pancreatitis due to pancreatic cysts
    • Intracranial berry aneurysms – affects up to 16% of people and may lead to a subarachnoid haemorrhage if they rupture
    • Mitral valve prolapse
    • Aortic root dilatation

ARPKD

The presentation of ARPKD varies significantly:

  • Perinatal features:
    • Abdominal distention due to renal enlargement
    • Oligohydramnios and pulmonary hypoplasia
    • Potter’s facies (flattened nose, micrognathia, low-set ears) – due to oligohydramnios
  • Neonatal features – at birth:
    • Palpable kidneys
    • Mild liver disease
  • Features in infancy and childhood:
    • Palpable kidneys
    • Hepatomegaly – may progress to portal hypertension and varices, hypersplenism, and hepatosplenomegaly
  • Marked liver disease

Investigations

Screening for ADPKD

Relatives of patients with ADPKD may be screened with an abdominal ultrasound.

Investigations in ADPKD

Investigations include:

  • Full blood count (FBC):
    • May show elevated haemoglobin as polycystic kidneys can produce excess erythropoietin
    • Urea and electrolytes (U&Es) and estimated glomerular filtration rate (eGFR):
    • Creatinine and eGFR may be normal in early stages
  • Renal ultrasound scan – the test of choice. ADPKD is diagnosed if there is a positive family history and:
    • ≥2 unilateral or bilateral renal cysts at <30 years
    • ≥2 cysts in each kidney at 30-59 years
    • ≥4 cysts in each kidney at >60 years
    • If no family history, then >10 cysts must be present in each kidney
  • MRI/CT:
    • May be considered if a renal ultrasound is equivocal
    • May also be considered to identify intracranial berry aneurysms
  • Genetic testing:
    • Not routinely performed

Management

ADPKD

There is no cure for ADPKD. Management involves:

  • Blood pressure control
  • Management of complications such as UTIs, renal stones, and loin pain
  • Renal replacement therapy may be necessary if end-stage renal disease (ESRD) develops
  • Tolvaptan (a vasopressin V2 receptor antagonist) may be considered if:
    • Patients have chronic kidney disease stage 2 or 3 at the start of treatment
    • There is evidence of rapidly progressive disease

Complications

Chronic kidney disease

PKD makes up for around 10% of people on dialysis for ESRD.

Hepatic cysts

Hepatic cysts are the most common extra-renal manifestation. They do not typically cause liver failure and may be asymptomatic, but in some patients, they can cause problems due to mass effects, such as abdominal pain.

Cardiovascular disease (CVD)

Both PKD and CKD cause hypertension which is associated with an increased risk of myocardial infarction and stroke. Furthermore, patients with PKD may have mitral valve prolapses, aortic regurgitation, and a dilated aortic root.

Intracranial aneurysms

Intracranial aneurysms may be found in up to 6% of patients without a family history of brain aneurysms and up to 16% of patients with a family history. These may rupture leading to a subarachnoid haemorrhage (SAH). A severe or unusual headache in a patient with PKD should raise suspicion of SAH.

Pregnancy complications

There is an increased risk of gestational hypertension and pre-eclampsia in patients with PKD, which are associated with adverse foetal and maternal outcomes.

Prognosis

  • Around 50% of patients with PKD will go on to develop ESRD and require renal replacement therapy
  • ADPKD 1 is associated with more severe disease and progression
  • Cardiovascular disease is the most common cause of death in ADPKD

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