Nephrotic Range Proteinuria Definition
Nephrotic-range proteinuria is defined as ≥3.5 g/24 hours (or ≥3,500 mg/day) in adults, which corresponds to a protein-to-creatinine ratio (PCR) ≥3,500 mg/g or ≥3.5 g/g. 1, 2, 3
Standard Measurement Thresholds in Adults
- 24-hour urine collection: Protein excretion rate (PER) ≥3,500 mg/day defines nephrotic-range proteinuria 4, 1
- Spot urine protein-to-creatinine ratio (PCR): ≥3,500 mg/g (or ≥3.5 g/g) is the equivalent threshold 4, 5, 6
- Albumin-specific measurements: Albumin excretion rate (AER) ≥2,200 mg/day or albumin-to-creatinine ratio (ACR) ≥2,200 mg/g corresponds to nephrotic-range albuminuria 4, 3
The conversion between total protein and albumin measurements is clinically important: a total protein excretion of 3.5 g/day is equivalent to albumin excretion of approximately 2.2 g/day in diabetic kidney disease. 3
Pediatric Thresholds
- Children require body surface area adjustment: ≥40 mg/m²/hour on timed collection 1, 2
- Spot urine in children: First morning protein-to-creatinine ratio ≥2 g/g (or ≥2,000 mg/g) 1, 2
The spot urine PCR has replaced 24-hour collections as standard practice in pediatrics due to practical advantages and good correlation with timed collections. 1
Important Clinical Context
Nephrotic-range proteinuria alone does not equal nephrotic syndrome. The complete nephrotic syndrome requires the triad of: 1, 2, 5
- Proteinuria ≥3.5 g/24 hours
- Serum albumin <3.0 g/dL in adults (≤2.5 g/dL in children)
- Edema
Critical Caveats to Avoid Misdiagnosis
Nephrotic syndrome can occur without nephrotic-range proteinuria in specific circumstances: 7
- When concurrent liver disease reduces albumin synthesis (e.g., hepatic amyloidosis), patients may develop full nephrotic syndrome with proteinuria <3.5 g/day
- The steady-state protein excretion reaches a lower threshold despite severe glomerular permeability defects because albumin production is impaired
The historical 3.5 g/24-hour threshold was selected arbitrarily but has been validated through clinical outcomes research showing it correlates with increased risk of end-stage renal disease and other complications. 3, 8
Terminology Update
The term "nephrotic-range" is no longer used for staging albuminuria in the KDIGO classification system. 4 Instead, use:
- A3 (Severely Increased Albuminuria): ACR ≥300 mg/g, which is distinct from and lower than traditional nephrotic-range thresholds
- The designation "nephrotic-range" remains clinically important but requires specification of whether full nephrotic syndrome is present 4
Prognostic Significance
Patients with proteinuria >3.8 g/day face 35% risk of end-stage renal disease within 2 years, compared to only 4% risk for those with proteinuria <2.0 g/day. 1 Even in patients with severely impaired renal function during pre-dialysis care, nephrotic-range proteinuria confers a 3.89-fold increased risk for rapid renal function decline. 8