Primary glomerular diseases
Talia Weinstein MD PhD
Sourasky Medical Center
‫נ‬
FSGS
• FSGS has become the leading cause of primary nephrotic
syndrome in adults
• The appearance of new forms of FSGS has led to the
approach that FSGS is seen today as a clinico-pathologic
syndrome, comprising diverse distinct diseases with
different etiologies
• The approach to the diagnosis of FSGS is problematic
because the morphologic features are non-specific and can
occur in a variety of conditions or may be superimposed on
other glomerular processes
FSGS - Pathology
• The sine qua non of FSGS is the presence of
increased amounts of extracellular matrix
• Typical pathologic features include segmental
glomerular scars
• Immunofluorescence is negative or positive only
for IgM and C3
• A ominous sign is the presence of tubular atrophy
or interstitial inflammatory cells
What is FSGS?
•Idiopathic FSGS is the primary manifestation
of a specific renal disease
•FSGS is a defined lesion that occurs after
stimulation by a variety of causes
•FSGS is a common final pathway of
glomerular obliteration that occurs after myriad
lesions of the kidney
• The diagnosis of FSGS is further complicated by
the existence of a primary (or idiopathic) form and
many secondary forms
• Before a diagnosis of primary FSGS can be
reached, secondary forms must be carefully
excluded
• These include genetic mutations, viral infection,
drug toxicity, as well as a large group of FSGS
caused by intrarenal vasodilatation and increased
glomerular capillary pressure secondary to
reduced renal mass or hemodynamic stress
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Primary (idiopathic) FSGS
HIV-associated nephropathy
Heroin-associated nephropathy
Familial FSGS: mutations in a-actinin, podocin,
mitochondrial cytopathies
Drug toxicity: pamidronate, interferon- a, lithium
Secondary FSGS: a) due to reduced functional
nephrons: unilateral agenesis, dysplasia, reflux
nephropathy, sequela to cortical necrosis. b) due to
hemodynamic stress: obesity, sickle cell anemia
Diabetes mellitus, hypertension
Nonspecific scarring: focal proliferative GN,
hereditary nephritis, membranous nephropathy
Clinical presentation
• Glomerular proteinuria is invariably
present, but may be either nephrotic or subnephrotic
• Hypertension and hematuria may also be
present
• Progression to to renal insufficiency and
end-stage renal disease occurs; spontaneous
remission occurs less commonly
• Accounts for 7% of glomerular lesions in
children and up to 35% of lesions in adults
presenting with the nephrotic syndrome
• The prevalence in blacks is 2 to 4 times that
in whites
• Despite similar degrees of renal
insufficiency at presentation, patients with
secondary FSGS have a 5-year renal
survival of 80% compared with 50% for
patients with primary FSGS
• The therapeutic approach to secondary FSGS
depends upon the underlying condition
• Correction of the underlying process such as
surgical repair of reflux, should be sought
• In patients with reduced renal mass (such as
agenesis, hypertension), maneuvers to reduce
glomerular capillary pressure (ACEI/ARB) are
offered
• Steroids are uniformly ineffective in familial
forms and secondary FSGS, and may even
promote weight gain and sclerosis in patients with
obesity and latent diabetes
Therapy
In view of the potential toxicity of the drugs used to treat
idiopathic MN, the decision to initiate therapy is based
in part on an understanding of the natural history of
untreated patients with this disorder:
- spontaneous remission of proteinuria occurs in 510%
- partial remission (< or = 2 gr/d) occurs in 25-40%
- the incidence of end stage renal disease is about 14%
at 5 years, 35% at 10 years, and 41% at 15 years
• Risk factors for progressive disease:
- men >50 years with the nephrotic syndrome
- extensive duration of heavy proteinuria
- patients with an elevated serum creatinine
- on biopsy glomerular scarring and TI disease
Therefore immunosuppressive agents should be
considered only in those patients most at risk
• Corticosteroids
• Cytotoxic agents
cyclophosphamide
chlorambucil
• Cyclosporine
• Mycofenolate Mofetil (MMF)
Nephritic syndrome
Hematuria
Red blood cell casts
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Micro/macrohematuria
May follow URTI
High IgA in serum
IgA found in mesangium on IF