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Genetic cystic, interstitial and tumorous renal disease

Including: Autosomal dominant and recessive polycystic kidney disease; tuberous sclerosis type 1 + 2; Von-Hippel-Lindau’s disease; Bardet-Biedl’s syndrome


Autosomal dominant polycystic kidney disease (ADPKD)

  • Type 1 and 2
  • Genetics of ADPKD
    • Both autosomal dominant
    • Genes are called PKD1 (Type 1 – this encodes polycystin 1 on chromosome 16) and PKD2 (Type 2 – encode polycystin 2on chromosome 4)  – these proteins are important in renal tubular cell differentiation
  • Presentation of ADPKD
    • Flank or loin pain
    • Macro/microscopic haematuria
    • Proteinuria
    • Hypertension
    • Polyuria
    • Headache/neurology from subarachnoid haemorrhage
    • Symptoms associated with cysts in other tissues
    • Causes roughly 5-10% of CKD
  • Work-up of ADPKD
    • USS to make the diagnosis
    • If positive family history: 2 cysts in either kidney is diagnostic if <30 years old, between 30-60 4 cysts in total is diagnostic, if>60 8 cysts in total is diagnostic
    • If negative family history: <30 5 cysts in total, 30-60 5 cysts in total and >60 8 cysts in total is diagnostic of ADPKD
    • Patients with a ADPKD and a FH of SAH will need screening MRI brains to monitor for berry aneurysm
    • Genetic testing
  • Complications (and treatment) of ADPKD
    • Hypertension: ACE-I
    • CKD: Dialysis or transplant
    • Cyst haemorrhage: analgesia and hydration, nephrectomy is situation is dire
    • Cyst infection: antibiotics (normally longer course due to poor penetrance)
    • Nephrolithiasis As per any no ADPKD patient
    • Extra renal cysts (hepatic, pancreatic, mesenteric, seminal etc) – puncture/de-roof/remove
    • Mitral valve prolapse – aortic regurgitation – as per non-ADPKD patient
    • Diverticular disease/hernias – as per non-ADPKD patient


Autosomal recessive polycystic kidney disease

  • Autosomal recessive
  • PKHD1 gene on chromosome 6 encoding polyductin and fibrocystin
  • Present with very early onset CKD, hepatic fibrosis with portal hypertension


Medullary cystic kidney disease

  • Autosomal dominant
  • MCKD-1 and 2 genes encoding renal cilia proteins – causes small cysts at corticomedullary junction
  • Nocturia, polydipsia and polyuria, can develop hyperuricaemia
  • Most get end-stage renal disease by 60


Tuberous sclerosis 1 and 2

  • Multi-system hamartomatous disease
  • Autosomal dominant – mutations in TSC1 (type 1) and TSC2 (type 2) tumour suppressor genes- protein is hamartin.
  • Type 2 is more common
  • Renal angiomyolipomas, skin changes (hamartomas, shagreen patches, ungal fibromata) and seizures. Can have cystic kidney disease also
  • Renal lesions need surveillance, as does BP (for HTN) and renal function (CKD)- normally done via an annual specialist review with renal USS or CT.


Von-Hippel-Lindau’s disease

  • Autosomal dominant
  • Multisystem masses both benign and malignant – retinal angiomatosis, phaeochromocytoma, renal tumours (RCC), Lindau tumours, pancreatic tumours
  • VHL gene (short arm of Chr 3) inactivation (tumour suppressor) leading to abundance of vascular growth factors
  • Need VHL genetic testing to confirm
  • MDT approach


Bardet-Biedl’s syndrome

  • Autosomal recessive
  • Retinitis pigmentosa, polydactyl, mental retardation, hypogenitalism and obesity
  • Renal: renal dysplasia and abnormal calyces


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