What are the diagnostic criteria for Nephrotic Syndrome (NS)?

From the Guidelines

Nephrotic syndrome is diagnosed when a patient presents with the triad of heavy proteinuria (>3.5g/24 hours), hypoalbuminemia (<30 g/l), and peripheral edema, as defined by the most recent guideline 1. The diagnostic criteria for Nephrotic Syndrome (NS) include:

• Heavy proteinuria, defined as urinary protein excretion exceeding 3.5 grams per 24 hours in adults or protein-to-creatinine ratio >2000mg/g (or >300mg/mmol) on a spot urine sample
• Hypoalbuminemia, typically manifested as serum albumin levels below 30 g/l
• Peripheral edema, usually dependent, affecting the lower extremities when upright and periorbital area when recumbent Additional findings that support the diagnosis include:
• Hyperlipidemia (elevated cholesterol and triglycerides)
• Lipiduria (fat bodies in urine)
• Hypercoagulability due to urinary loss of anticoagulant proteins The most recent guideline 1 emphasizes the importance of assessing total urinary protein excretion and estimated glomerular filtration rate (eGFR) in patients with glomerular diseases. Further evaluation, including kidney biopsy, may be necessary to determine the underlying cause of NS, which could be primary kidney diseases like minimal change disease, focal segmental glomerulosclerosis, or membranous nephropathy, or secondary to systemic conditions such as diabetes, lupus, or certain medications 1. Early diagnosis is crucial as it guides specific treatment approaches and helps prevent complications like thromboembolism, infections, and progressive kidney damage.

From the Research

Diagnostic Criteria for Nephrotic Syndrome (NS)

The diagnostic criteria for Nephrotic Syndrome (NS) include:

• Oedema, substantial proteinuria (> 3.5 g/24 hours) and hypoalbuminaemia (< 30 g/L) 2
• Hypoalbuminemia, severe proteinuria, and peripheral edema, frequently in conjunction with hyperlipidemia 3
• Urine total protein excretion greater than 3.5 g/d or total protein-creatinine ratio greater than 3.5 g/g, low serum albumin level, high serum cholesterol level, and peripheral edema 4

Key Features of Nephrotic Syndrome

Key features of NS include:

• Proteinuria should be documented by a quantitative measurement e.g. urine protein: creatinine ratio (PCR) or albumin: creatinine ratio (ACR) 2
• PCR > 300-350 mg/mmol indicates nephrotic range proteinuria 2
• Low serum albumin, usually associated with edema, hyperlipidemia, and lipiduria 5
• Hyperlipidaemia, thromboembolism and an increased risk of infection 2

Special Considerations

Special considerations in the diagnosis of NS include:

• The 3.5g/24h threshold for proteinuria was selected arbitrarily and might not be reached in certain cases despite severe defects in glomerular permeability 5
• In cases where albumin synthesis is decreased secondary to concurrent liver disease, a steady state of renal protein excretion may be reached at a lower threshold than 3.5g/24h despite severe defects in glomerular permeability 5
• Evaluation should assess for secondary causes of NS, including diabetes, amyloidosis, systemic lupus erythematosus, hematologic malignancies, and infections 6