American Urological Association - Medullary Cystic Disease/Nephronophthisis
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Medullary Cystic Disease/Nephronophthisis

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  • Hereditary form of tubulointerstitial disease characterized by formation of corticomedullary cysts.
  • Secondary to mutations in ciliary proteins.
  • Divided into NPHP types I (juvenile), II (infantile), III (adolescent) by onset of ESRD.
  • Mutations in NPHP1 accounts for ~85% of NPHP type 1 which maps in chr 2q13; NPHP2 encodes for inversin responsible for NPHP type II and maps to chr 9p22-31; and NPHP3 encodes for nephrocystin-3 responsible for NPHP type III.
  • MCKD type 1 progress to ESRD at 6th decade whereas type II progress to ESRD at 3rd decade.
  • MCKD1 maps to chr 1q21 and MCKD2 encodes uromodulin which maps to chr 16p12; both MCKD have autosomal dominant inheritance.
  • Clinical:
    • NPHP1 and II patients present with polyuria and polydipsia due to salt wasting; concentration defect; anemia disproportionate to the level of renal insufficiency, and growth retardation; hyperuricemia and gout.
    • 10-15% retinitis pigmentosa (Senior-Loken syndrome).
    • NPHP II manifests with oligohydramnios, hypertension, VSD.
    • MCKD I and II manifest with polyuria and polydipsia due to salt wasting; concentration defect; hyperuricemia and gout.
  • Gross:
    • Kidneys are small at presentation due to cortical atrophy.
    • Cysts congregate at the corticomedullary junction and range up to 1 cm in diameter
      (image A) and (image B).
    • Cyst formation does not appear to progress as the disease progresses.
  • Histology:
    • Cysts lined by flattened to cuboidal epithelium.
    • Chronic tubulointerstitial inflammation with tubular atrophy, interstitial fibrosis, and glomerulosclerosis.
    • Interstitium fibrosis and prominent lymphoid infiltrate that may worsen with time.