Kidney nontumor / medical renal
Developmental & cystic diseases
Nephronophthisis
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PubMed Search: Nephronophthisis kidney
- 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
- 1:50,000
- Most common genetic cause of pediatric end stage renal disease (ESRD)
- Mutations in NPHP genes (produce nephrocystins in cilia / basal body structures, (Eur J Hum Genet 2009;17:406, J Am Soc Nephrol 2007;18:1855), which cause defects in signaling mechanisms that result in defects of planar cell polarity and tissue maintenance (J Am Soc Nephrol 2009;20:23)
- 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.
- 4 year old girl with basal ganglia calcification and pancreatic lipomatosis (Arch Pathol Lab Med 1988;112:630)
- Renal transplant for ESRD (Pediatr Transplant 2008;12:878)
- Normal or small kidneys with firm, granular cortices and corticomedullary cysts
- Infantile forms have enlarged kidneys with cortical cysts
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Cysts at corticomedullary
junction, tubular cysts
and interstitial infiltrate
- 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
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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)
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)
- Mutations in NPHP2 and NPHP3 genes (Kidney Int 2009;75:839), also associated with retinitis pigmentosa, intellectual disability, 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)
- Homogenously thickened tubular (NOT glomerular) basement membrane, split into thin lamellae, reticulated or disintegrated
Images hosted on other servers:
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
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
