What is the difference between Urine Protein-to-Creatinine Ratio (UPCR) and Albumin-to-Creatinine Ratio (ACR) in assessing proteinuria?

Differences Between UPCR and ACR in Assessing Proteinuria

Urine Albumin-to-Creatinine Ratio (ACR) is preferred over Urine Protein-to-Creatinine Ratio (UPCR) for assessing proteinuria in most clinical scenarios, particularly for detecting early kidney damage and stratifying risk in chronic kidney disease. 1

Key Differences Between ACR and UPCR

Measurement Focus

• ACR: Specifically measures albumin, the predominant protein lost in most kidney diseases
• UPCR: Measures all proteins in urine, including albumin and non-albumin proteins

Clinical Applications

• ACR is preferred for:

  • Screening and monitoring early kidney damage
  • Risk stratification in CKD
  • Monitoring diabetic kidney disease
  • Detection of glomerular injury

• UPCR may be useful for:

  • Quantifying heavy proteinuria
  • Conditions with significant non-albumin proteinuria (tubular proteinuria, overflow proteinuria)
  • When albumin measurement is unavailable

Diagnostic Thresholds

• ACR thresholds:

  • Normal: <30 mg/g
  • Moderately increased (formerly "microalbuminuria"): 30-300 mg/g
  • Severely increased (formerly "macroalbuminuria"): >300 mg/g

• UPCR thresholds:

  • Normal: <150-200 mg/g
  • Clinical proteinuria: >200 mg/g

Relationship Between Measurements

• The relationship between ACR and UPCR is non-linear 2
• At lower levels of proteinuria, non-albumin proteins constitute a higher proportion of total protein
• As proteinuria increases, albumin becomes the predominant protein, making ACR and UPCR more closely correlated at higher levels 2

Evidence Supporting ACR

1. Superior Sensitivity for Early Detection:

   • ACR can detect low levels of albumin excretion that may be missed by UPCR
   • Albumin is the most important protein lost in most kidney diseases 1

2. Better Standardization:

   • Albumin assays are more standardized than total protein assays
   • KDIGO guidelines recommend laboratories report ACR rather than albumin concentration alone 1

3. Stronger Prognostic Value:

   • ACR has shown slightly better performance in predicting IgA nephropathy progression compared to UPCR 3
   • ACR accurately predicts kidney and cardiovascular risks in population studies 1

4. Preferred in Guidelines:

   • Current KDIGO guidelines recommend ACR as the preferred test for adults and children 1

Practical Considerations

Sample Collection

• First morning void is preferred for both tests to minimize orthostatic proteinuria 1, 4
• Both can be performed on random urine samples, though with more variability
• Factors affecting results include:
  • Exercise (increases both albumin and total protein)
  • Urinary tract infection
  • Hematuria
  • Menstruation 1

Interpretation Challenges

• Sex and body weight differences:

  • Women typically have lower urinary creatinine excretion, resulting in higher ACR and UPCR values
  • Lower muscle mass leads to lower creatinine excretion and higher ratios 1

• Conversion between measurements:

  • Converting between ACR and UPCR is challenging due to non-linear relationship
  • Equations exist but have moderate sensitivity and specificity 5

Clinical Recommendations

1. Use ACR for screening and risk stratification:

   • Particularly in diabetes, hypertension, and early CKD
   • More sensitive for detecting low-grade but clinically important albuminuria 1

2. Consider UPCR when:

   • ACR testing is unavailable
   • Evaluating conditions with significant non-albumin proteinuria
   • Quantifying heavy proteinuria

3. Confirm positive screening tests:

   • Positive dipstick results should be confirmed with quantitative ACR or UPCR 1
   • Confirm elevated ACR with a first morning void sample 1

4. Monitor consistently:

   • Use the same test (ACR or UPCR) for longitudinal monitoring
   • Assess at least annually in people with CKD, more frequently with higher risk of progression 1

Common Pitfalls to Avoid

• Terminology confusion: The term "microalbuminuria" should no longer be used; instead use "moderately increased albuminuria" 1

• Misinterpreting variability: Small fluctuations are common and don't necessarily indicate disease progression 1

• Ignoring factors affecting measurements: Exercise, infection, menstruation, and posture can all affect results 1

• Inconsistent monitoring: Switching between ACR and UPCR during monitoring can lead to misinterpretation of changes

• Storage issues: Samples for albumin measurement should not be frozen at -20°C as this can result in loss of measurable albumin 1