What are nephritic (inflammation of the kidneys), sub-nephrotic, and nephrotic (kidney disease characterized by severe proteinuria) range proteinuria?

Definitions of Proteinuria Ranges

Proteinuria is categorized into three clinically distinct ranges based on quantitative measurements: sub-nephrotic (<3.5 g/24h), nephrotic-range (≥3.5 g/24h), and nephritic-range (typically <3 g/24h with active urinary sediment). These thresholds guide diagnostic evaluation, predict prognosis, and determine treatment intensity.

Nephrotic-Range Proteinuria

Nephrotic-range proteinuria is defined as protein excretion ≥3.5 g/24 hours (or ≥3,500 mg/day) in adults, which corresponds to a spot urine protein-to-creatinine ratio (PCR) ≥3,500 mg/g 1. For albumin-specific measurements, this translates to an albumin excretion rate (AER) ≥2,200 mg/day or albumin-to-creatinine ratio (ACR) ≥2,200 mg/g 1.

Pediatric Thresholds

• Children require body surface area adjustment with a threshold of ≥40 mg/m²/hour on timed collection 1
• A first morning spot urine PCR ≥2 g/g (≥2,000 mg/g) indicates nephrotic-range proteinuria in children 2, 1
• Serum albumin ≤2.5 g/dL (not <3.0 g/dL) should be maintained as the diagnostic threshold for nephrotic syndrome in children, as this has been the standard for 50 years of clinical trials 2

Critical Distinction

Nephrotic-range proteinuria alone does NOT equal nephrotic syndrome. Full nephrotic syndrome requires the triad of: (1) proteinuria ≥3.5 g/24h, (2) serum albumin <3.0 g/dL in adults (≤2.5 g/dL in children), and (3) edema 1, 3. Hyperlipidemia and thromboembolism risk are common associated features 3.

Important Exception

In patients with concurrent liver disease (such as hepatic amyloidosis), nephrotic syndrome can occur with proteinuria below 3.5 g/24h because reduced albumin synthesis lowers the steady-state threshold despite severe glomerular permeability defects 4.

Sub-Nephrotic Proteinuria

Sub-nephrotic proteinuria refers to protein excretion between 150 mg/day and 3.5 g/24h, representing pathological but non-nephrotic levels 5, 6. This range encompasses:

• Mild proteinuria: 150 mg/day to 1 g/24h
• Moderate proteinuria: 1-2 g/24h
• Heavy sub-nephrotic proteinuria: 2-3.5 g/24h

Clinical Significance

• Proteinuria <2 g/24h suggests tubulointerstitial or vascular disorders are as likely as glomerular disease 5
• Proteinuria 2-3.5 g/24h typically indicates glomerular pathology but without the full nephrotic syndrome 5
• The KDIGO A3 category (severely increased albuminuria) uses ACR ≥300 mg/g as the threshold, which is far below nephrotic range but carries significant cardiovascular and renal risk 2

Nephritic-Range Proteinuria

Nephritic-range proteinuria typically refers to protein excretion <3 g/24h accompanied by active urinary sediment (hematuria, red blood cell casts, dysmorphic RBCs) and often acute kidney injury. This pattern characterizes inflammatory glomerular diseases rather than pure permeability defects 7.

Key Features Distinguishing Nephritic from Nephrotic

• Proteinuria severity: Usually <3 g/24h (though overlap exists) 7
• Urinary sediment: Active with hematuria and cellular casts (nephritic) vs. bland with lipiduria (nephrotic) 7
• Presentation: Acute onset with hypertension and edema from volume overload (nephritic) vs. gradual onset with edema from hypoalbuminemia (nephrotic) 7
• Underlying pathology: Inflammatory/proliferative glomerulonephritis (nephritic) vs. podocyte injury with increased permeability (nephrotic) 7

Common Nephritic Causes

• Post-infectious glomerulonephritis 6
• IgA nephropathy (though can present with nephrotic-range proteinuria) 8
• Lupus nephritis classes III and IV (proliferative forms) 2
• ANCA-associated vasculitis 7

Updated KDIGO Terminology

The 2020 KDIGO nomenclature consensus eliminated "nephrotic-range" as a staging term for albuminuria, instead using A3 (Severely Increased Albuminuria) for ACR ≥300 mg/g 2. However, the designation "nephrotic-range" remains clinically important for differential diagnosis and requires specification of whether full nephrotic syndrome is present 2, 1.

Current KDIGO Albuminuria Categories

• A1: Normal to mildly increased (ACR <30 mg/g) 2
• A2: Moderately increased (ACR 30-299 mg/g) 2
• A3: Severely increased (ACR ≥300 mg/g) 2

The Canadian Society of Nephrology recommends adding an A4 category for nephrotic-range proteinuria (ACR >2,220 mg/g or >220 mg/mmol) because this threshold is widely used in differential diagnosis and identifies particularly high-risk groups 2.

Prognostic Implications

Proteinuria >3.8 g/day carries a 35% risk of end-stage renal disease within 2 years, compared to only 4% risk for proteinuria <2.0 g/day 1, 7. This dramatic difference underscores why quantifying proteinuria severity is essential for risk stratification and treatment decisions.

Measurement Methods

• Preferred: 24-hour urine collection for protein excretion rate (PER) or albumin excretion rate (AER) 2
• Practical alternative: Spot urine protein-to-creatinine ratio (PCR) or albumin-to-creatinine ratio (ACR), ideally from first morning void 2
• Albumin measurement is preferred over total protein because it can be standardized and is more accurate in the lower range 2