DR Medhat MRCP

Focal Segmental Glomerulosclerosis (FSGS)
Causes
1) Primary (Idiopathic) FSGS :
- Males > females (with additional high risk of progressive CKD in males).
- It`s 3X more common in black patients 2/3 cases of N.S in black patients.
Mutation in apolipoprotein-1 gene
- As 1ry FSGS recurs after transplantation (often immediately), a circulating
factor capable of disturbing glomerular permeability has been implicated in
some patients.
- Candidates include the soluble form of the urokinase receptor (suPAR) and
VEGF.
2) Secondary FSGS :
a) Hyperfiltration (most common cause) :
Presentations
Morbid obesity.
Diabetic nephropathy, pre-eclampsia , sickle cell disease.
b) Nephron mass reduction ( hyperfiltration of the remaining nephrons) :
Renal dysplasia , reflux nephropathy , renovasular disease, nephrectomy
c) Infection (podocyte invasion):
HIV [HIV-associated nephropathy (HIVAN)].
Parvovirus 19.
d) Drugs (podocyte toxicity):
Heroin.
Pamidronate, lithium & α- interferon.
e) Any cause of glomerular disease with progressive scarring e.g :
Membranous GN, IgAN, Alport syndrome, thrombotic microangiopathy,
vasculitis.
f) Familial (inherited FSGS) : Genetic mutation in the following genes :
Transient receptor potential cation 6 channel (TRPC6) : AD , child N.S.
α -actinin 4 (protein for podocyte integrity) : AD , low proteinuria , CKD.
NPHS2 gene encoding for Podocin: (podocin is a protein for slit
diaphragm) : AR , responsible for 1/3 of steroid-resistant N.S in children.
Nephrotic syndrome (80%)
Microscopic hematuraia (50%)
Hypertension (40%)
CKD (25 % of cases present with CKD at presentation)
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