From the Guidelines
Nephrotic syndrome is diagnosed based on the presence of proteinuria > 3.5 g/d and serum albumin < 30 g/l, with or without edema, as defined by the KDIGO 2021 guideline for the management of glomerular diseases 1. The diagnosis of nephrotic syndrome involves a combination of clinical evaluation, laboratory tests, and sometimes kidney biopsy. Key diagnostic criteria include:
- Proteinuria exceeding 3.5g per day
- Low blood albumin levels (hypoalbuminemia)
- High cholesterol (hyperlipidemia)
- Swelling (edema), particularly in the legs, ankles, and around the eyes The cornerstone of diagnosis is a 24-hour urine collection to quantify protein excretion, though spot urine protein-to-creatinine ratio can also be used for initial screening 1. Blood tests are essential to measure albumin, cholesterol, and kidney function markers like creatinine and blood urea nitrogen (BUN). Urinalysis with microscopic examination helps detect protein and evaluate for red blood cells or casts. In many cases, especially when the cause isn't obvious or when treatment decisions depend on knowing the specific kidney pathology, a kidney biopsy is performed, as recommended by the KDIGO 2021 guideline 1. This involves removing a small piece of kidney tissue for microscopic examination to identify the underlying disease process. Additional tests may include antinuclear antibody (ANA), complement levels, hepatitis panel, and HIV testing to identify potential causes, although the KDIGO 2021 guideline does not specify these tests as necessary for diagnosis 1. Early diagnosis is crucial as prompt treatment can prevent complications and slow progression of kidney damage. It's worth noting that an older study from 2007 defined nephrotic syndrome as presence of heavy proteinuria, hypoalbuminemia, and edema, with hypercholesterolemia commonly present 1, but the KDIGO 2021 guideline provides more specific and up-to-date criteria for diagnosis 1.
From the Research
Diagnosis of Nephrotic Syndrome
Nephrotic syndrome can be diagnosed based on characteristic medical symptoms and evidence of hypoalbuminemia and severe proteinuria 2. The diagnosis is typically made by confirming heavy proteinuria and hypoalbuminemia, with patients presenting with edema and fatigue, without evidence of heart failure or severe liver disease 3.
Clinical Features
The clinical features of nephrotic syndrome include:
- Peripheral edema
- Heavy proteinuria (> 3.5 g/24 hours)
- Hypoalbuminemia (< 30 g/L)
- Hyperlipidemia
- Thromboembolism
- Increased risk of infection 4, 3, 5
Diagnostic Tests
Diagnostic tests for nephrotic syndrome include:
- Urine protein: creatinine ratio (PCR) or albumin: creatinine ratio (ACR) to document proteinuria
- Measurement of serum albumin and lipid levels
- Renal biopsy to establish the underlying cause of glomerular disease 4, 3, 5
Evaluation for Secondary Causes
Evaluation for secondary causes of nephrotic syndrome should be performed, including:
- Assessment for diabetes mellitus
- Systemic lupus erythematosus
- Amyloidosis
- Hematologic malignancies
- Infections 4, 5
Role of Renal Biopsy
Renal biopsy is often recommended to establish the underlying cause of glomerular disease, although it may be most useful in patients with suspected underlying systemic lupus erythematosus or other renal disorders 4, 3, 5. In children, biopsy is typically not needed if the patient improves with steroid treatment, but is warranted if the patient does not improve or has frequent recurrences 5.