Definition of Nephrotic-Range Proteinuria
Nephrotic-range proteinuria is defined as ≥3.5 g/24 hours (or protein-to-creatinine ratio ≥3,500 mg/g) in adults, and ≥40 mg/m²/hour (or spot urine protein-to-creatinine ratio ≥2 g/g) in children. 1, 2
Standard Adult Thresholds
The following measurements all define nephrotic-range proteinuria in adults:
- 24-hour urine collection: ≥3.5 g/24 hours (≥3,500 mg/day) 1, 3
- Spot urine protein-to-creatinine ratio (PCR): ≥3,500 mg/g (≥3.5 g/g) 1
- Albumin-specific measurements: Albumin excretion rate ≥2,200 mg/day or albumin-to-creatinine ratio ≥2,200 mg/g 1, 3
The albumin thresholds are lower than total protein thresholds because albumin comprises approximately 60-70% of total urinary protein in nephrotic syndrome. 3
Pediatric Thresholds
Children require body surface area adjustment with different measurement approaches:
- Timed urine collection: ≥40 mg/m²/hour 1, 2, 4
- First morning spot urine PCR: ≥2 g/g (≥2,000 mg/g) 1, 2
- Urine dipstick: 3+ protein or greater 4
The spot urine PCR has replaced 24-hour collections as standard of care in children due to good correlation and practical advantages. 2
Critical Distinction: Proteinuria vs. Syndrome
Nephrotic-range proteinuria alone does NOT equal nephrotic syndrome. 1, 2
Full nephrotic syndrome requires the complete triad:
- Proteinuria ≥3.5 g/24 hours (adults) or ≥40 mg/m²/hour (children) 2, 5
- Serum albumin <3.0 g/dL in adults or ≤2.5 g/dL in children 1, 2, 4
- Edema 1, 5
Additional features often present include hyperlipidemia and increased thromboembolism risk, but these are not required for diagnosis. 5
Important Clinical Caveats
Albumin assay variability matters clinically: A serum albumin of 2.5 g/dL measured by BCG method equals approximately 2.0 g/dL by BCP method. 2
Exceptions to the 3.5 g/day threshold exist: Patients with concurrent liver disease (such as hepatic amyloidosis) may present with full nephrotic syndrome despite proteinuria <3.5 g/24 hours because reduced hepatic albumin synthesis allows a steady state to be reached at lower protein excretion levels. 6 In these cases, the diagnosis relies on demonstrating severe glomerular permeability defects despite lower absolute proteinuria values.
Prognostic Significance
The degree of proteinuria carries major prognostic implications:
- Proteinuria >3.8 g/day: 35% risk of end-stage renal disease within 2 years 1, 2
- Proteinuria <2.0 g/day: Only 4% risk of end-stage renal disease within 2 years 1, 2
Terminology Update
KDIGO classification no longer uses "nephrotic-range" terminology for staging albuminuria, instead using "A3 (Severely Increased Albuminuria)" for ACR ≥300 mg/g. 1 However, the designation "nephrotic-range" remains clinically important when specifying whether full nephrotic syndrome is present. 1