Comprehensive Serology Workup for Nephrotic Syndrome
A complete nephrotic syndrome workup should include serum albumin, lipid profile, urinary protein quantification, and targeted serological testing to identify underlying causes, with genetic testing reserved for specific cases of suspected hereditary disease.
Initial Laboratory Assessment
Basic Nephrotic Syndrome Confirmation
- Urinary protein quantification:
- 24-hour urine protein (nephrotic range: >3.5 g/day)
- Spot urine protein-to-creatinine ratio (PCR)
- Serum albumin (typically <3.0 g/dL in nephrotic syndrome)
- Lipid profile (total cholesterol, triglycerides, HDL, LDL)
- Complete blood count
- Serum creatinine and estimated GFR
- Serum electrolytes, BUN
Primary Serological Workup
- Antinuclear antibodies (ANA)
- Complement levels (C3, C4)
- Anti-neutrophil cytoplasmic antibodies (ANCA)
- Hepatitis B and C serology
- HIV testing
Disease-Specific Serological Testing
For Suspected Membranous Nephropathy
- Anti-phospholipase A2 receptor (PLA2R) antibodies
- Positive in approximately 80% of primary membranous nephropathy cases 1
For Suspected Lupus Nephritis
- Anti-double-stranded DNA antibodies
- Anti-Smith antibodies
- Anti-SSA/Ro and anti-SSB/La antibodies
For Suspected Systemic Diseases
- Anti-streptolysin O (ASO) titer
- Cryoglobulins
- Serum and urine protein electrophoresis
- Serum free light chains (for suspected amyloidosis or multiple myeloma)
- Rheumatoid factor
For Infectious Causes
- Syphilis serology
- Toxoplasmosis serology
- Cytomegalovirus (CMV) serology
- Rubella serology
- Measles serology
- Herpes simplex virus (HSV1, HSV2) serology
- Herpes zoster virus (HZV) serology
- Bordetella pertussis serology (in selected cases) 2
Genetic Testing Considerations
Genetic testing should be considered in specific scenarios:
- Familial kidney disease
- Syndromic features
- Steroid-resistant focal segmental glomerulosclerosis (FSGS)
- Early onset disease (especially in children)
- Congenital nephrotic syndrome 2
For adults with steroid-resistant nephrotic syndrome and FSGS on biopsy, 11-24% will have disease-causing variants primarily in type IV collagen or podocyte genes 2.
Additional Testing Based on Clinical Presentation
For Patients with Features of Congenital Nephrotic Syndrome
- Extended evaluation for dysmorphic features
- Skeletal abnormalities assessment
- Genital examination
- Ophthalmological examination
- Hearing test
- Neurological examination 2
For Secondary FSGS Evaluation
- Thyroid function tests
- Serum IgG level
- Ionized calcium, phosphate, alkaline phosphatase, PTH, 25(OH) vitamin D3 2
Imaging Studies
- Renal ultrasound (to assess kidney size and echogenicity)
- Cardiac ultrasound (in severe cases to assess for effusions)
- Ultrasound of abdomen and pleural space (to assess for ascites, effusions, thrombosis) 2
Important Clinical Considerations
- Kidney biopsy is often necessary for definitive diagnosis, especially in adults with unexplained proteinuria >3.0 g per gram creatinine 3
- For patients with FSGS, classification into primary, genetic, secondary, or undetermined cause is crucial for treatment decisions 2
- Patients with non-nephrotic range proteinuria (<3.5 g/day) or with nephrotic-range proteinuria but albumin >3.0 g/dL should undergo workup for secondary causes of FSGS 2
- Genetic testing should be performed at specialized centers with relevant expertise 2
Remember that identification of the underlying cause of nephrotic syndrome is critical for determining appropriate treatment and prognosis, as immunosuppressive therapy may be beneficial for primary forms but potentially harmful in secondary or genetic forms of the disease.