What is the diagnostic workup for Nephrotic Syndrome (a condition characterized by severe proteinuria, hypoalbuminemia, hyperlipidemia, and edema)?

From the Guidelines

The workup for nephrotic syndrome should begin with a thorough history and physical examination, followed by laboratory tests including urinalysis with microscopy, urine protein-to-creatinine ratio, serum albumin, lipid panel, and renal function tests, as recommended by recent guidelines 1. The initial evaluation should include a 24-hour urine collection for protein quantification, with nephrotic-range proteinuria defined as >3.5g/24 hours in adults.

• Complete blood count, serum electrolytes, and complement levels (C3, C4) should be measured to rule out secondary causes and assess the severity of the disease.
• Serologic testing should include antinuclear antibody, anti-double-stranded DNA, hepatitis B and C serologies, HIV testing, and serum and urine protein electrophoresis to identify potential underlying causes.
• Renal ultrasound is recommended to assess kidney size and structure and rule out obstruction, as suggested by the guidelines 1. A kidney biopsy is often necessary to determine the underlying pathology, especially in adults, those with atypical presentations, or when secondary causes are suspected, as it provides valuable information for treatment decisions 1.
• The biopsy helps distinguish between minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and other glomerular diseases, which is crucial for guiding treatment approaches. This comprehensive evaluation is essential because treatment approaches differ significantly based on the underlying cause, and early diagnosis can prevent complications such as thromboembolism, infections, and progressive kidney damage, as highlighted in the guidelines 1.

From the Research

Diagnosis of Nephrotic Syndrome

• Nephrotic syndrome is defined by a triad of clinical features: oedema, substantial proteinuria (> 3.5 g/24 hours) and hypoalbuminaemia (< 30 g/L) 2
• 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

Causes of Nephrotic Syndrome

• The most common cause in children is minimal change glomerulonephritis 2
• In white adults, nephrotic syndrome is most frequently due to membranous nephropathy 2
• In populations of African ancestry the most common cause of nephrotic syndrome is focal segmental glomerulosclerosis 2
• Diabetic nephropathy is the most common multisystem disease that can cause nephrotic syndrome 2

Workup for Nephrotic Syndrome

• Urgent referral to a nephrologist (ideally within 2 weeks) is necessary 2
• A renal biopsy is usually performed to establish what form of glomerular disease is responsible 2
• Additional tests may be undertaken to assess if nephrotic syndrome is secondary to another disorder e.g. systemic lupus erythematosus or amyloidosis 2
• Patients typically present with periorbital oedema or dependent pitting oedema 2, 3

Complications of Nephrotic Syndrome

• Important complications of NS include venous thrombosis and hyperlipidemia 3
• Other potential complications include infection and acute kidney injury 3
• Spontaneous acute kidney injury from NS is rare but can occur as a result of the underlying medical problem 3

Treatment of Nephrotic Syndrome

• Treatment consisting of sodium restriction, fluid restriction, loop diuretics, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, and careful assessment for possible disease complications is appropriate for most patients 3
• Immunosuppressive treatment, including corticosteroids, is often used for NS, although evidence is lacking 3
• Routine prophylactic treatment to prevent infection or thrombosis is not recommended 3