Page 487 - Concise Pathology for Exam Preparation ( PDFDrive )

472 SECTION II Diseases of Organ Systems

• It differs from minimal change disease in the following ways:
• Greater incidence of haematuria and hypertension
• Non-selective proteinuria
• Poor response to steroids and progression to chronic glomerulonephritis

Pathogenesis
The epithelial damage which is a hallmark of FSGS is caused by different mechanisms:
1. Genetic mechanisms: Genetic defects that affect the integrity of the normal glomerular
filtration barrier (eg, mutations in the Nephrosis, Congenital, Finnish Type or NPHS
genes, NPHS1 and NPHS2, which encode for the proteins nephrin and podocin, respec-
tively; mutations in the gene encoding the podocyte actin-binding protein a-actinin-4;
and mutation in the gene encoding Transient receptor potential calcium channel-6 or
TRCP6, a podocyte protein responsible for maintaining calcium flux).
2. Circulating factors: Presence of an unknown circulating factor is thought to be responsible
for the epithelial damage as it is noted that the disease recurs even after transplantation.

Pathology
Light microscopy
• Segmental involvement
• Collapse of basement membrane, hyalinosis and lipid droplets in the affected segment,
gradually leading to global sclerosis (global means entire glomerulus). The hyalinosis
and sclerosis is due to entrapment of plasma proteins (a result of excessive membrane
permeability) and increased ECM deposition.
• Unaffected glomeruli show increased mesangial matrix/mesangial proliferation.
Electron microscopy
• Loss of foot processes
• Detachment of epithelial cells and denudation of glomerular basement membrane
Immunofluorescence
IgM and C 3 deposits in sclerotic areas.
Clinical Course
One-fourth patients develop intractable massive proteinuria ending in renal failure within
2 years.
HIV-Associated Nephropathy

• Seen in 5–10% of HIV-infected patients.
• Shows features of severe collapsing FSGS with foci of cystically dilated tubules filled
with proteinaceous material. Inflammation and fibrosis may be seen in later stages.
• Electron microscopy shows a large number of tubuloreticular inclusions in endothelial
cells. These inclusions are basically interferon a-mediated alterations in the epithelial
endoplasmic reticulum.

Membranoproliferative Glomerulonephritis (MPGN)
• As the name suggests MPGN is characterized by proliferation of glomerular cells and
changes in the GBM. The proliferation is predominantly mesangial, thus the condition
is also called mesangiocapillary glomerulonephritis.
• It is responsible for 5–10% cases of idiopathic nephrotic syndrome. It may sometimes
arise secondary to SLE, Hepatitis B and C, CLL, a1 AT deficiency, endocarditis, systemic
infections, HIV and schistosomiasis.
Clinical Features
• Proteinuria in the nephrotic or non-nephrotic range
• Haematuria

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