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

Urine Protein-to-Creatinine Ratio (UPCR) vs Albumin-to-Creatinine Ratio (ACR)

The Albumin-to-Creatinine Ratio (ACR) is the preferred test for assessing proteinuria in most clinical scenarios, particularly for detecting early kidney damage and stratifying risk in chronic kidney disease, while Protein-to-Creatinine Ratio (UPCR) remains useful in specific conditions where non-albumin proteins may be significant. 1

Key Differences Between ACR and UPCR

What Each Test Measures

• ACR: Specifically measures albumin, the predominant protein lost in most kidney diseases
• UPCR: Measures total protein excretion, including albumin and other proteins

Clinical Applications

ACR Advantages

• More sensitive for detecting low levels of albumin excretion that may be missed by UPCR 1
• Better standardized assays compared to total protein assays 1
• Superior for early detection of kidney damage, particularly in:
  • Diabetic kidney disease
  • Hypertensive kidney disease
  • Early stages of CKD 2, 1
• Slightly better performance in predicting kidney and cardiovascular risks in population studies 1

UPCR Advantages

• More useful when significant non-albumin proteinuria is suspected 2
• May be more appropriate for:
  • Tubular disorders
  • Multiple myeloma (detecting Bence Jones proteins)
  • Other conditions with significant non-albumin proteinuria 2, 1

Guideline Recommendations

The KDIGO guidelines recommend:

1. ACR as the first choice for initial testing of proteinuria 2
2. UPCR as the second choice when ACR is not available 2
3. Using the same test (either ACR or UPCR) consistently for longitudinal monitoring 1

Interpretation and Clinical Significance

Classification Thresholds

• Normal: ACR < 30 mg/g
• Moderately increased albuminuria (formerly "microalbuminuria"): ACR 30-300 mg/g 1
• Severely increased albuminuria: ACR > 300 mg/g

Correlation Between Tests

• ACR, UPCR, and 24-hour urine collections are highly correlated (correlation coefficients: 0.71-0.87) 3
• For UPCR values > 50 mg/g, conversion equations to ACR demonstrate moderate sensitivity (91%, 75%, 87%) and specificity (87%, 89%, 98%) for screening and classification 4
• However, the association between UPCR and ACR is inconsistent for UPCR values < 50 mg/g 4

Practical Considerations

When to Use Each Test

• Use ACR for:

  • Screening for early kidney damage
  • Diabetic kidney disease monitoring
  • Risk stratification in CKD
  • Longitudinal monitoring when ACR was initially used

• Consider UPCR when:

  • Non-albumin proteinuria is suspected
  • Specific urine proteins need to be identified
  • ACR is not available
  • Longitudinal monitoring when UPCR was initially used

Factors Affecting Measurements

• Exercise, urinary tract infection, hematuria, and menstruation can affect both ACR and UPCR results 1
• Sex and body weight differences impact urinary creatinine excretion, resulting in higher values in women and individuals with lower muscle mass 1

Monitoring Recommendations

• Monitor ACR or UPCR at least annually in people with CKD 2
• Increase monitoring frequency for individuals at higher risk of progression 2
• Small fluctuations in results are common and do not necessarily indicate disease progression 2
• Do not switch between ACR and UPCR during monitoring as this can lead to misinterpretation of changes 1

Clinical Outcomes

Both ACR and UPCR perform similarly as predictors of renal outcomes and mortality in patients with CKD 5, but ACR has slightly better performance in predicting CKD progression in some studies 3.