Nephrotic Syndrome Diagnosis and Management

Definition and Diagnostic Criteria

Nephrotic syndrome is defined by a classic triad of massive 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 (periorbital, dependent, or involving body cavities), as suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) and Kidney International guidelines 1, 2
Hypoalbuminemia directly results from urinary protein loss and is a defining characteristic of nephrotic syndrome, with a decrease of 1.0 g/dL in serum albumin increasing the odds of morbidity by 89% and mortality by 137% 1
The severity of hypoalbuminemia correlates with disease severity and prognosis, highlighting the importance of monitoring serum albumin levels in patients with nephrotic syndrome 1

Confirm proteinuria: Protein-to-creatinine ratio ≥3.5 g/g or 24-hour urine collection ≥3.5 g/day, with the 24-hour urine collection considered the traditional gold standard for measuring proteinuria, and the protein-to-creatinine ratio in a single urine sample being a more practical and convenient method 1, 3
Measure serum albumin: Values <3.0 g/dL confirm hypoalbuminemia, with different methods of measuring serum albumin (bromocresol green vs bromocresol purple) affecting results 1, 2
Assess for edema: Periorbital, dependent, or involving body cavities, with edema being a common symptom of nephrotic syndrome 1, 2
Initial screening for proteinuria can be done using a dipstick test, with values >1 g/L (2+) providing a reasonable assessment, and a positive dipstick test result (≥1+, 30 mg/dL) should be confirmed with a protein-to-creatinine ratio 3

Hyperlipidemia, including hypercholesterolemia and hypertriglyceridemia, is commonly present in nephrotic syndrome, with the risk of thromboembolic events increasing significantly when serum albumin falls below 2.9 g/dL 1, 2, 4
Massive proteinuria (>5 g/24h) is associated with more severe outcomes, and persistent proteinuria >1 g/day (PCR ≥60 mg/mmol or ≥100 mg/mmol) justifies referral to a nephrologist for consideration of renal biopsy and possible immunosuppressive treatment 3, 5

Biochemical tests, including complete blood count, electrolytes, creatinine, urea, proteins, cholesterol, triglycerides, and glucose, are essential in the diagnostic workup, and evaluation of calcium-phosphorus metabolism is recommended 4
Imaging studies, such as abdominal and pleural ultrasound, echocardiogram, and X-rays, may be necessary to assess for complications, and genetic testing may be considered in selected cases 4
Renal biopsy is generally indicated to establish the underlying glomerular disease responsible for nephrotic syndrome, and should include light microscopy, immunofluorescence, and/or immunohistochemistry, and electron microscopy 4
Treatment decisions are guided by diagnostic criteria, with restriction of salt and fluids according to volume status recommended, and monitoring for complications, such as thromboembolic risk, lipid profile, and infection surveillance, is essential 1, 2, 4, 6