From the Guidelines
Diagnosing focal segmental glomerulosclerosis (FSGS) requires a comprehensive approach including clinical evaluation, laboratory tests, and kidney biopsy, with the definitive diagnosis made through kidney biopsy showing focal and segmental scarring of glomeruli with areas of sclerosis. The diagnostic process should start with evaluating for proteinuria, typically >3.5g/day, often in nephrotic range, serum creatinine levels to assess kidney function, serum albumin (usually decreased), and lipid profile (often elevated) 1.
Key Diagnostic Steps
- Urinalysis to show protein but minimal blood cells
- Screening for secondary causes of FSGS such as HIV, hepatitis B and C, and autoimmune disorders
- Genetic testing for patients with family history of kidney disease or early-onset FSGS 1
- Imaging studies like kidney ultrasound to assess kidney size and rule out other structural abnormalities
- Kidney biopsy examined under light microscopy, immunofluorescence (typically negative or nonspecific), and electron microscopy (showing foot process effacement)
Considerations
- Evaluate for an underlying cause and exclude secondary forms of FSGS 1
- Consider genetic screening where appropriate to exclude genetic forms of FSGS 1
- The presence of nephrotic syndrome is a critical factor in determining the approach to diagnosis and treatment, with proteinuria > 3.5 g/d and serum albumin <30 g/l being key indicators 1
- A comprehensive diagnostic approach is necessary because FSGS can be primary (idiopathic) or secondary to other conditions, and treatment strategies differ based on the underlying cause 1
From the Research
Diagnosis of Focal Segmental Glomerulosclerosis
To diagnose focal segmental glomerulosclerosis (FSGS), several methods can be employed, including:
- Renal biopsy: considered the gold standard for diagnosis, as it allows for the direct examination of kidney tissue 2
- Biomarkers: various biological molecules have been evaluated as potential markers to enhance the diagnosis of FSGS, some of which are associated with the pathogenesis of the disease 2
- Electron microscopy (EM): examination of foot process effacement on EM can help differentiate between primary and secondary FSGS, with primary FSGS typically showing widespread foot process effacement and secondary FSGS showing segmental foot process effacement 3, 4
- Clinical correlations: dividing FSGS into nephrotic syndrome-associated (NS-associated) and non-nephrotic syndrome-associated (NNS-associated) groups can help distinguish between primary and secondary FSGS, with adult patients presenting with NS, an FSGS lesion on light microscopy, and extensive foot process effacement on EM examination likely to have primary FSGS 4
Key Characteristics for Diagnosis
Some key characteristics to consider when diagnosing FSGS include:
- Presence of nephrotic syndrome: primary FSGS is typically characterized by the presence of nephrotic syndrome, while secondary FSGS is often characterized by the absence of nephrotic syndrome 3, 4
- Degree of foot process effacement on EM: primary FSGS typically shows widespread foot process effacement, while secondary FSGS shows segmental foot process effacement 3, 4
- Presence of risk factors for secondary FSGS: patients with risk factors such as hypertension, diabetes, or obesity may be more likely to have secondary FSGS 3
Limitations and Challenges
Diagnosing FSGS can be challenging due to:
- Variability in biopsy findings: some biopsies may lack a considerable number of sclerotic glomeruli, making diagnosis difficult 2
- Overlap between primary and secondary FSGS: failure to accurately differentiate between primary and secondary FSGS can result in unnecessary immunosuppressive treatment 3
- Need for further evaluation: reductions in proteinuria may be associated with greater kidney survival, but further evaluation is needed to determine the best course of treatment 5