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Polycystic Kidney Disease (PKD)

  • AD-PKD – MC, syn Adult PKD, Potter’s type II PK
  • AR-PKD – syndrome Infantile PKD, microcystic KD, Potter’s type I

Epidemiology

  • MC inherited genetic disease
  • General pop – 1/1000
  • Dialysis pts – 5-10% in EU + USA

Etiology

  • Hereditary AD disease with dominant translation of the gene
  • Approx 100% penetration of the pathological gene – develop disease at 70 yo
  • Absence of chromosomal aberrations + karyotype deviations
  • Absence of linkage with HLA
  • Genetic heterogeneity – more than 1 pathologic gene responsible for disease

Genetics – localisation of the pathologic gene

  • PKD1 – Chromosome 16p, 3’HVR (1985)
    • Linkage with locus of gene of α-globin molecule and RBC-phosphoglycolatphosphatase
    • 85% of EU pop
  • PKD2 – Chromosome 4q13-23 (1993)
    • 15% of EU pop
  • 3rd likely locus is chromosome 22 or 11

Pathogenesis

  • Place and origin cysts is from the tubular component
  • Theories
    • Virchow – inflammation and retention hypothesis (1855)
      • Prolif of epithelial cells → obstruction of tubules → intratubular retention of urine
    • Disembryogenetic theories – change of normality during embryogenic life of pt, there is no connection bw proximal and distal tubule, leaving a blind part of tubule
      • Hilderbrandt, McKenna
  • Current opinion
    • Change in compliance of tubular BM – softer and easily elongates
    • Tubular cellular hyperplasia causes tubular obstruction
    • Enlarged tubular cellular secretion and fluid accumulation
    • Polycystin – 1+2 proteins encoded by
  • Cysts can originate in proximal tubule or LOH

Pathomorphology

  • Enlargement of kidney – size + weight markedly increased (Normal – 10-12cm; 150g)
  • Secondary reduction of normal kidney function – severe kidney failure
  • Content of cyst – clear fluid

Clinical features

  • Onset is before birth, however CF at 30 years
  • Symptoms due to main disease
    • Lumbar pain, dull
    • Renal colic
    • Enlarged kidneys
    • Arterial HTN
    • Proteinuria (mild, <1.5g/l) – no edema
    • Hematuria
  • Symptoms due to complications of cyst
    • Chronic pyelonephritis
    • Inflam/rupture of cyst
    • Nephrolithiasis
    • Neoplasm
  • Symptoms of combine anomalies
  • Combined abnormalities
    • Polycystic liver disease, panc cysts, cysts in ovaries, testes, lungs
    • Brain artery aneurysms, cardiac valves, intestinal diverticula, hernias
    • Brain haemorrhage
    • Liver cyst haemorrhage and inflam
  • Symptoms during pregnancy
    • Nephropahia gravidarum
    • UTI

Diagnosis

  • Diagnostic def – presence of >5 cysts in kidneys, always Bilateral
  • Diagnostic criteria
    • Main
      • Cysts in both kidneys
      • Positive familial history
    • Secondary
      • Cysts in liver (hallmark) and other organs
      • Enlarged kidneys, brain aneurysms, CRF
  • Methods
    • History
    • Physical exam – 50% pts have enlarged palpable kidneys
    • Ultrasound – gold standard
    • CT/MRI – only in severe cases
    • Genetic/DNA analysis – can be made in utero
      • Ethical problems of early dx

Differential diagnosis

  • Solitary kidney cysts (common in >50yo)
  • Hydronephrosis
  • Cystic disease of renal sinus
  • Acquired CKD
  • Multicystic dysplastic kidney
  • ARPKD
  • Renal tumours

Treatment

  • Prophylaxis of disease and complications
  • Etiology/pathogenetic treatment is impossible
  • Treatment of renal disease – of hypertension, of cysts (by rupture), of comps (PLN, purulent cysts)
  • Treatment of combined abnormalities and their complications
    • Of brain aneurysms and haemorrhage
    • Of cardiac failure (valvular abnormalities are normally mild)
  • Treatment of complications in pregnant women
  • Treatment of CRF – dialysis + transplantation
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