Kidney tumor - cysts, children, adult benign
Cystic nonneoplastic lesions
Nephronophthisis

Author: Mandolin Ziadie, M.D. (see Authors page)

Revised: 12 January 2017, last major update December 2011

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PubMed Search: Nephronophthisis [title] kidney

Cite this page: Nephronophthisis. PathologyOutlines.com website. http://pathologyoutlines.com/topic/kidneytumornephronophthisis.html. Accessed February 20th, 2017.
Definition / General
  • Group of autosomal recessive disorders characterized by corticomedullary cysts, atrophy and interstitial fibrosis
  • "Phthisis" (Greek): dwindling or wasting away
  • Also referred to as juvenile nephronophthisis medullary cystic kidney disease complex
Epidemiology
  • 1:50,000
  • Most common genetic cause of pediatric end stage renal disease (ESRD)
Pathophysiology
Clinical Features
  • Juvenile form: most common; presents in childhood with polyuria / polydipsia due to cortical and tubulointerstitial damage that progresses to chronic renal failure in 5 - 10 years; no gender preference; also anemia and growth retardation; 12% associated with retinitis pigmentosa
  • Adolescent form: similar to juvenile with later (mean, 19 years) presentation
  • Infantile: bilateral disease due to cortical cysts with renal failure by 3 years of age; may have extrarenal presentation including retinitis pigmentosa, hepatic fibrosis, skeletal / CNS malformations, situs inversus, etc.
Case Reports
Treatment
Gross Description
  • Normal or small kidneys with firm, granular cortices and corticomedullary cysts
  • Infantile forms have enlarged kidneys with cortical cysts
Gross Images

Images hosted on other servers:

Cysts at corticomedullary
junction, tubular cysts
and interstitial infiltrate

Micro Description
  • Severe tubular atrophy with thick basement membranes, interstitial fibrosis and chronic inflammation
  • Minimal to advanced glomerulosclerosis
  • Cysts at corticomedullary border lined by flattened or cuboidal epithelium
  • Liver biopsy may show congenital hepatic fibrosis
Micro Images

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Tubules with thickened basal membrane (PAS)

Dilated tubules, thickened basal membrane (PAS)

Deformed tubules
with thickened basal
membrane in fibrotic
stroma (PAS)

Dilated tubules with lymphocytic infiltrate (PAS)

Tubular basement
membrane thickening
and cystic tubular
enlargement



End stage renal disease:

Preserved glomeruli with individual glomerular cysts, tubulointerstitial fibrosis, hypertrophic tubules, lymphocytic infiltrate

Tubulointerstitial
fibrosis, tubular cysts
and lymphocytic
infiltrate (PAS)

Extensive obliteration of glomeruli
and sclerotic glomerli, interstitial
fibrosis, atrophic tubules and
chronic inflammation (PAS)

Molecular / Cytogenetics Description
  • Mutations in NPHP2 and NPHP3 genes (Kidney Int 2009;75:839), also associated with retinitis pigmentosa, mental retardation, cerebellar ataxia, bone anomalies and liver fibrosis
  • Juvenile subtype associated with mutations in NPHP1 (OMIM 256100) (chromosome 2q), 4 (chromosome 1p)
  • Infantile subtype associated with NPHP2 (chromosome 9q)
  • Adolescent subtype associated with NPHP3 (chromosome 3q)
Electron Microscopy Description
  • Homogenously thickened tubular (NOT glomerular) basement membrane, split into thin lamellae, reticulated or disintegrated
Electron Microscopy Images

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Tubules:

Thickened tubular basement membrane

Grid like
degeneration of
tubular basement
membrane

Atrophic tubules
with partly thickened,
partly missing
basal lamina

Basal membrane shows
thickening, splitting,
grid like degeneration
or complete absence


Collapsed glomeruli
centrally, Bowman’s
capsule is filled with
amorphous material

Partially atrophic tubule with thickened basal membrane

Newly formed lamellar basal membrane

Cyst wall lined
with collecting duct
epithelium, basal
membrane is lost



Glomeruli:

Thickened glomerular
basal membrane with
lacuna, periglomerular
fibrosis

Mild periglomerular fibrosis,
thickened tubules with
fragmented basal lamina,
lymphocytes