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Kidney non-tumor

Primary glomerular diseases

Congenital nephrotic syndrome


Reviewers: Nikhil Sangle, M.D. (see Reviewers page)
Revised: 15 April 2012, last major update April 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
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● Heterogenous conditions with nephrotic syndrome within first 3 months of life
● Onset between 3–12 months is called infantile nephrotic syndrome
● No response to steroids or immunosuppressive therapy
● Divided into Finnish type and diffuse mesangial sclerosis (see below), but may also be a part of a more generalized syndrome or caused by a perinatal infection (Pediatr Nephrol 2009;24:2121)

Diagrams
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Normal glomerular capillary and capillary wall

Treatment
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● Renal transplant

Differential diagnosis
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● Infectious causes: congenital syphilis or toxoplasmosis
● Idiopathic: minimal change disease, diffuse mesangial hypercellularity, focal and segmental glomerulosclerosis
● Other rare causes include hemolytic-uremic syndrome or sytemic lupus erythematosus


Finnish type

General
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● Autosomal recessive disorder (OMIM #256300)
● Also called NPHS1, Finnish congenital nephrosis
● 1.5% of cases of nephrotic syndrome in childhood
● Occurs in 1 per 10,000 newborns in Finland, lower incidence elsewhere (1 in 50,000 in North America)
● Nephrin protein is produced by glomerular podocyte, encoded by NPHS1 at 19q13.1; normally expressed at slit diaphragm of glomerular podocyte, but missing or defective (due to misfolding or defective intracellular trafficking) in patients with Finnish type syndrome
● Can diagnose in utero via genetic testing; suggested by heavy proteinuria in utero, increased AFP levels in maternal serum or amniotic fluid
● At birth, large placentas, proteinuria, edema, infections, premature birth, mild facial / limb abnormalities and poor development
● Doesn’t respond to steroids or immunosuppression; death without kidney transplant
● Dramatic improvement with transplant, but 20% have recurrence of nephrotic syndrome, which may respond to rituximab (Pediatr Transplant 2011 Jun 15 [Epub ahead of print])

Case reports
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● Genetically confirmed cases in Korea (J Korean Med Sci 2009;24 Suppl:S210)

Gross description
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● Enlarged kidneys due to tubular dilation and interstitial edema

Micro description
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● Proximal and distal tubular ectasia with flattening of tubular epithelium, microcysts with or without tubular PAS+ hyaline casts, glomerulosclerosis, mesangial hypercellularity, occasional immature glomeruli
● May evolve to focal and segmental glomerulosclerosis
● At renal failure stage, is interstitial fibrosis, global glomerulosclerosis and tubular atrophy

Micro images
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Patchy interstitial edema and cystically dilated tubules with attenuated epithelium


Mesangial hypercellularity and diffuse increase of mesangial matrix

   
Various immunostains

Immunofluorescence
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● Non-specific IgM and C3 in mesangium and capillaries

Electron microscopy description
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● Obliteration (effacement) of foot processes

Electron microscopy images
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Wide effacement of epithelial foot processes


Diffuse mesangial sclerosis

General
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● Clinically and genetically heterogeneous group of disorders in non-Finnish patients (J Am Soc Nephrol 2010;21:1209)
● Early onset of severe proteinuria (50% within months 0-2, 50% in months 3–9 months), with rapid progression to end stage renal disease by age 3 years
● May be associated with WT1 abnormalities and Denys-Drash syndrome (OMIM #256370), PLCE1 mutations (Nephrol Dial Transplant 2008;23:1291) or be isolated (Pediatr Nephrol 2009;24:1013)
● Normal placenta, no premature births, but is associated with cataracts and corneal clouding, aniridia, microencephaly, mental retardation and hypertelorism
● Does not recur after transplantation

Case reports
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● Two cases of isolated diffuse mesangial sclerosis with WT1 mutations (J Korean Med Sci 2006;21:160)

Micro description
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● Diffuse mesangial sclerosis; tubular atrophy with focal tubular dilatation and interstitial fibrosis

Micro images
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Mesangial sclerosis

   
WT1-associated

Immunofluorescence
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● Non-specific staining with mesangial deposits of IgM, C3 and C1q

Electron microscopy description
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● Obliteration of foot processes, basement membrane thickening and increase in mesangial matrix

End of Kidney non-tumor > Primary glomerular diseases > Congenital nephrotic syndrome

Ref Updated: 4/12/12


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