6.
FOCAL SEGMENTAL GLOMERULOSCLEROSIS
- FSGS is NOT a single disease but a diagnostic term for a clinical-pathologic syndrome with multiple
causes and pathogenic mechanisms, as well as somewhat limited therapeutic options
- The most important clinical features are proteinuria, which may be nephrotic or non-nephrotic; and
slow progressive loss of kidney function
From scar tissue formation of the glomerulus
Proteins, lipids trapped build up inside glomeruli hyalinosis scar tissue
SEGMENTAL means only a part of/ segment of the glomerulus is affected
FOCAL means out of all of the glomerulus in the kidney only some are affected
CLASSIFICATION
Primary (idiopathic) FSGS
Familial (hereditary) FSGS
Secondary FSGS with:
o HIV disease
o IV drug abuse (heroin abuse)
o Other drugs (e.g. pamidronate, interferon, anabolic steroids)
o Glomerulomegaly
o Morbid obesity
o Sickle cell disease
o Myeloproliferative neoplasia
o Cyanotic congenital heart disease
o Hypoxic pulmonary disease
o Kidney abnormalities
o Vesicouretic reflux
CLINICAL FEATURES
- Proteinuria is the hallmark feature of all forms
o Can be from 1-2g per day, to >10g per day
- Hematuria (50% of cases)
- 1/3 of patients present with some degree of Renal insufficiency
- Hypertension (more common in adults)
- Progression:
o Slowly leads to loss of kidney function and ESKD after several years (can take 10 years)
o Degree of proteinuria is a predictor of long-term clinical outcome:
Non-nephrotic-range proteinuria correlates with more favorable renal survival
o Patients with a higher serum creatinine levels have poorer renal survival
Dx
- Lab data for nephrotic syndrome
- Low eGFR
- Anemia (corresponding to the level of renal insufficiency)
- Normal levels of complement
- Us - shows normal or reduced size of kidney
- CT can rule out presence of other abnormalities
- Kidney biopsy is the method of diagnosis
- LIGHT MICROSCOPY
o Focal and segmental glomerular sclerosis or consolidation
Hyalinosis of the glomeruli
o Based on the character and glomerular distribution of lesion, five major structural variants
can be recognized that correlate prognosis:
1. Collapsing FSGS
2. Tip lesions FSGS
3. Cellular FSGS
4. Perihilar FSGS
5. NOS FSGS - (not otherwise specified)
- IMMUNOFLUORESCENCE MICROSCOPY
o In all of the variants, non-sclerotic glomeruli/ segments usually show no staining for
immunoglobulins or complement
o Sclerotic segments typically show irregular staining for C3, C1q and IgM
- ELECTRON MICROSCOPY
o The ultrastructural features of FSGS are nonspecific
o Plays an important role in the Dx of FSGS by helping identify other causes for glomerular
scarring that can be mistaken for FSGS by light microscopy alone (E.g. Fabry disease)
o Foot process effacement is less extensive in some forms of secondary FSGS that in
idiopathic
Tx
- Angiotensin inhibitors
o ACE inhibitor and Angiotensin II receptor blockers (ARBs)
ACEi decrease proteinuria and rate of progression to ESKD
Regardless anti-inflammatory or immunosuppressive therapy are employed, they
should be indicated even despite side effects of hyperkalemia and reduction in GFR
o Before immunomodulatory or immunosuppressive therapy is indicated - careful evaluation should
be undertaken to exclude possibility of underlying cause
Patients with Secondary and Hereditary FSGS are unlikely to benefit from
immunosuppressive therapy
Patients with Sub-nephrotic range proteinuria and normal eGFR have a general good
prognosis, and Tx should be focused on blood pressure control
Use maximal tolerated dosages of RAAS blockers
Patient with Idiopathic FSGS and Nephrotic syndrome glucocorticoids
or immunosuppressive therapy
Patients with FSGD respond less than patients with MCD to corticosteroids and
immunosuppressive Tx
If not calcineurin inhibitor.
May need transplant in 10 years
