Proteinuria Classification
Proteinuria is classified using a three-category system (A1, A2, A3) based on albumin or protein excretion rates, with specific thresholds defined by the 2020 KDIGO consensus guidelines that replace outdated terms like "microalbuminuria" and "macroalbuminuria." 1
Standard Classification System
The KDIGO framework categorizes proteinuria into three levels regardless of whether kidney disease is present:
Category A1: Normal to Mildly Increased
- Albumin excretion rate (AER) <30 mg/day 1
- Albumin-to-creatinine ratio (ACR) <30 mg/g (<3 mg/mmol) 1
- Protein excretion rate (PER) <150 mg/day 1
- Protein-to-creatinine ratio (PCR) <150 mg/g (<15 mg/mmol) 1
Category A2: Moderately Increased
- AER 30–300 mg/day 1
- ACR 30–300 mg/g (3–30 mg/mmol) 1
- PER 150–500 mg/day 1
- PCR 150–500 mg/g (15–50 mg/mmol) 1
- The term "microalbuminuria" should be avoided and replaced with "moderately increased albuminuria" 1
Category A3: Severely Increased
- AER >300 mg/day 1
- ACR >300 mg/g (>30 mg/mmol) 1
- PER >500 mg/day 1
- PCR >500 mg/g (>50 mg/mmol) 1
- The terms "macroalbuminuria" and "clinical proteinuria" should be avoided 1
Nephrotic-Range Proteinuria (Subset of A3)
- AER >2200 mg/day 1
- ACR >2200 mg/g (>220 mg/mmol) 1
- PER >3500 mg/day 1
- PCR >3500 mg/g (>350 mg/mmol) 1
- Must specify whether nephrotic syndrome is present (hypoalbuminemia with edema and hyperlipidemia) 1
Measurement Methods and Terminology
Spot urine samples (ACR or PCR) have replaced 24-hour collections as the preferred method for detecting and monitoring proteinuria because they correct for hydration variations and are far more convenient than timed collections. 1
Preferred Measurement Terms
- Urinary albumin-creatinine ratio (ACR): from spot or timed collection; time of day should be noted 1
- Urinary protein-creatinine ratio (PCR): from spot or timed collection; time of day should be noted 1
- Albumin excretion rate (AER): requires timed collection; interval must be specified 1
- Protein excretion rate (PER): requires timed collection; interval must be specified 1
Terms to Avoid
- "Normoalbuminuria" (use "normal" instead) 1
- "Microalbuminuria" (use "moderately increased albuminuria") 1
- "Macroalbuminuria" (use "severely increased albuminuria") 1
- "Clinical proteinuria" or "overt proteinuria" (use "severely increased proteinuria") 1
Pathophysiologic Classification
Beyond quantitative thresholds, proteinuria can be classified by mechanism of origin:
Glomerular Proteinuria
- Characterized by excretion of high-molecular-weight proteins, predominantly albumin (66 kDa) 2, 3, 4
- Results from disruption of the glomerular filtration barrier 2, 5
- Albumin-to-β2-microglobulin ratio is high (1100–14,200) in pure glomerular disease 4
Tubular Proteinuria
- Characterized by excretion of low-molecular-weight proteins (<66 kDa) such as β2-microglobulin (15 Å Stokes radius) 2, 3, 4
- Results from impaired proximal tubular reabsorption via the megalin-cubilin complex 2, 5
- Albumin-to-β2-microglobulin ratio is low (1.0–13.3) in pure tubular dysfunction 4
- Total protein excretion is typically only moderately increased despite marked β2-microglobulin elevation 4
Mixed Proteinuria
- Contains both high- and low-molecular-weight proteins 3, 6
- Albumin-to-β2-microglobulin ratio is intermediate (33–163) 4
- Indicates combined glomerular and tubulointerstitial damage 6
Integration with CKD Staging
The CGA classification system combines Cause of disease, GFR category (G1–G5), and Albuminuria category (A1–A3) to stratify risk for adverse outcomes including mortality, kidney failure, and CKD progression. 1
- Ascertainment of CKD severity and prognosis from GFR alone, without albuminuria assessment, is not acceptable 1
- The three albuminuria categories are grouped with six GFR categories into four risk levels, typically displayed as a heat map 1
Critical Measurement Considerations
First morning void specimens are preferred for children and adolescents to avoid orthostatic proteinuria, while random daytime specimens are acceptable for adults. 7