From the Guidelines
Nephrotic syndrome is diagnosed based on the presence of heavy proteinuria (>3.5g/24 hours), hypoalbuminemia (<3.5g/dL), and edema, often accompanied by hyperlipidemia, as established by the most recent guidelines 1. To diagnose nephrotic syndrome, a comprehensive approach is necessary, focusing on clinical features, laboratory tests, and sometimes kidney biopsy. The diagnostic criteria include:
- Heavy proteinuria, which can be quantified through a 24-hour urine collection or estimated using a spot urine protein-to-creatinine ratio
- Hypoalbuminemia, with a serum albumin level less than 3.5g/dL
- Edema, which may be peripheral, periorbital, or abdominal (ascites)
- Hyperlipidemia, typically characterized by elevated cholesterol and triglycerides The diagnosis should begin with a thorough history and physical examination, followed by laboratory tests, including:
- Urinalysis to detect proteinuria
- Blood tests for serum albumin, lipid profile, renal function tests (BUN, creatinine), and complete blood count
- Additional serologic tests, such as complement levels, antinuclear antibodies, hepatitis panel, and HIV testing, may help identify underlying causes A kidney biopsy is often necessary to determine the specific glomerular disease causing nephrotic syndrome, especially in adults or when secondary causes are suspected, as emphasized by the KDIGO 2021 guideline 1. In pediatric patients, the definition of nephrotic syndrome may vary, with some guidelines suggesting a serum albumin level of ≤2.5 g/dL, but the most recent commentary suggests continuing to use this definition in the absence of evidence to support a change 1. The use of spot urine protein-to-creatinine ratio is established as the standard of care for children, with nephrotic-range proteinuria defined as a first morning UPCR of ≥2 g/g 1. Overall, a comprehensive evaluation is essential for accurate diagnosis and guiding appropriate treatment based on the underlying etiology of the nephrotic syndrome.
From the Research
Diagnostic Criteria for Nephrotic Syndrome (NS)
The diagnostic criteria for Nephrotic Syndrome (NS) include:
- Peripheral edema
- Heavy proteinuria, defined as urine total protein excretion greater than 3.5 g/d or total protein-creatinine ratio greater than 3.5 g/g 2
- Hypoalbuminemia, defined as a low serum albumin level, typically less than 30 g/L 3
- Hyperlipidemia, defined as a high serum cholesterol level 3, 2
Clinical Presentation
Patients with NS typically present with:
- Edema, often periorbital or dependent pitting oedema 3, 4
- Fatigue
- Proteinuria, which should be documented by a quantitative measurement, such as urine protein: creatinine ratio (PCR) or albumin: creatinine ratio (ACR) 3
- Hypoalbuminemia and hyperlipidemia, which can be confirmed by blood tests 3, 2
Diagnostic Evaluation
The diagnostic evaluation of NS should include:
- Urine tests to confirm heavy proteinuria, such as PCR or ACR 3, 2
- Blood tests to confirm hypoalbuminemia and hyperlipidemia 3, 2
- Renal biopsy, which may be useful in some cases to confirm an underlying disease or to identify idiopathic disease that is more likely to respond to corticosteroids 3, 5, 4
- Evaluation for secondary causes, such as diabetes mellitus, systemic lupus erythematosus, and medication adverse effects 3, 5, 4