What are the criteria for diagnosing nephrotic syndrome?

Diagnostic Criteria for Nephrotic Syndrome

Nephrotic syndrome is defined by the presence of heavy proteinuria (≥3.5 g/day in adults or ≥40 mg/m²/h in children), hypoalbuminemia (<3.0 g/dL in adults or <2.5 g/dL in children), and edema. 1

Core Diagnostic Criteria

For Adults:

1. Proteinuria:

   • ≥3.5 g/day or protein:creatinine ratio (PCR) >300-350 mg/mmol 2
   • This threshold was selected somewhat arbitrarily but remains the standard definition 3

2. Hypoalbuminemia:

   • <3.0 g/dL 1

3. Edema:

   • Typically periorbital (more noticeable in the morning)
   • Dependent pitting edema (more common later in the day) 2

For Children:

1. Proteinuria:

   • ≥40 mg/m²/h or
   • Urine protein:creatinine ratio (UPCR) ≥2 g/g 1
   • Albustix 3+ on at least 3 occasions within 1 week 1

2. Hypoalbuminemia:

   • ≤2.5 g/dL 1

   Note: While the 2021 KDIGO guideline suggested changing the definition to <3.0 g/dL for children, the KDOQI commentary recommends maintaining the traditional ≤2.5 g/dL threshold due to lack of evidence supporting this change. 1

Associated Features

These are commonly present but not required for diagnosis:

1. Hyperlipidemia:

   • Hypercholesterolemia
   • Hypertriglyceridemia 1, 4

2. Lipiduria 4

3. Increased risk of thromboembolism:

   • Risk increases when serum albumin falls below 2.9 g/dL 1
   • Particularly high risk in membranous nephropathy 5

4. Increased susceptibility to infections 6

Diagnostic Approach

1. Quantify proteinuria:

   • 24-hour urine collection for total protein
   • Spot urine protein:creatinine ratio (PCR) or albumin:creatinine ratio (ACR)
   • In children, spot UPCR has replaced 24-hour collections due to good correlation and ease of collection 1

2. Measure serum albumin:

   • Be aware of assay differences (bromocresol green vs. bromocresol purple) when interpreting results 1

3. Evaluate for underlying cause:

   • Renal biopsy is typically indicated in adults 2, 5
   • In children, empiric steroid trial is often initiated first; biopsy is reserved for steroid-resistant cases 5
   • Investigate for secondary causes (diabetes, lupus, amyloidosis, infections, malignancies) 2, 5

Special Considerations

1. Nephrotic syndrome without nephrotic-range proteinuria:

   • Can occur when albumin synthesis is decreased (e.g., concurrent liver disease)
   • A steady state of renal protein excretion may be reached at <3.5 g/day despite severe defects in glomerular permeability 3

2. Monitoring for complications:

   • Thromboembolism risk assessment
   • Lipid profile
   • Infection surveillance 6

Treatment Implications

The diagnosis of nephrotic syndrome often guides treatment decisions:

• In children with presumed minimal change disease, glucocorticoids are first-line therapy 5
• In adults, treatment depends on the underlying cause identified by biopsy 2
• Edematous states in idiopathic nephrotic syndrome are an FDA-approved indication for prednisone 7

The diagnostic criteria are essential for determining when to initiate specific therapies, such as in membranous nephropathy where treatment is recommended when proteinuria persistently exceeds 4 g/day for at least 6 months despite conservative therapy 1.