Urine Albumin-to-Creatinine Ratio (ACR) and Protein-to-Creatinine Ratio (PCR)
Urine albumin-to-creatinine ratio (ACR) is a standardized measurement that quantifies the amount of albumin in urine relative to creatinine, serving as a critical marker for kidney damage and an essential tool for diagnosing and monitoring chronic kidney disease (CKD). 1
What is ACR?
ACR measures the ratio of albumin to creatinine in a spot urine sample, typically expressed in mg/g. This ratio provides several advantages:
- Standardization: Accounts for urine concentration variability by indexing albumin to creatinine
- Convenience: Eliminates need for 24-hour urine collection
- Early detection: Identifies kidney damage before symptoms appear or GFR declines
- Risk stratification: Helps categorize patients by CKD severity and progression risk
ACR vs. PCR
While both ACR and PCR measure urinary protein excretion, they differ in important ways:
- ACR: Specifically measures albumin, the predominant protein in glomerular disease
- PCR: Measures all proteins in urine, including albumin and other proteins
Although PCR is still commonly used in clinical practice, guidelines increasingly recommend ACR as the preferred measurement for CKD assessment 1.
Clinical Interpretation of ACR Values
According to KDIGO and ADA guidelines, ACR values are categorized as follows:
| Category | ACR (mg/g) | Clinical Significance |
|---|---|---|
| Normal to mildly increased (A1) | <30 | Low risk |
| Moderately increased (A2) | 30-299 | Moderate risk (formerly called "microalbuminuria") |
| Severely increased (A3) | ≥300 | High risk (formerly called "macroalbuminuria") |
Clinical Applications of ACR
1. CKD Diagnosis and Staging
ACR is essential for CKD diagnosis and staging, used alongside estimated glomerular filtration rate (eGFR). The KDIGO CKD classification system uses both measures to create a heat map for risk stratification 1:
- Green: Very low risk
- Yellow: Moderate risk
- Orange: Moderate to high risk
- Red: Highest risk
2. Monitoring Disease Progression
ACR should be measured:
- Annually in adults with diabetes 1
- Every 6 months if eGFR <60 mL/min/1.73 m² and/or ACR >30 mg/g 1
- More frequently in patients at higher risk of progression 1
A sustained reduction in ACR of >30% is considered a surrogate marker of slowed kidney disease progression 1.
3. Cardiovascular Risk Assessment
Elevated ACR is independently associated with increased cardiovascular risk, making it valuable for comprehensive risk assessment 2.
Factors Affecting ACR Measurement
Several factors can influence ACR results, potentially leading to false positives 1:
- Physiological factors: Exercise, upright posture, fever
- Pathological conditions: Urinary tract infection, hematuria, heart failure
- Demographic factors: Age, race, gender, muscle mass
- Technical factors: Sample storage conditions, assay methods
Best Practices for ACR Testing
Sample collection: First morning urine is preferred due to better correlation with 24-hour protein excretion and lower intra-individual variability 1
Sample handling:
- Can be analyzed fresh
- Can be stored at 4°C for up to 1 week
- Can be stored at -70°C for longer periods
- Avoid freezing at -20°C (causes loss of measurable albumin) 1
Confirmation of results: Confirm abnormal results with 2 additional tests over 3-6 months before making a definitive diagnosis 1
Standardized reporting: Report as mg/g or mg/mmol of creatinine 1
ACR vs. Urine Dipstick Testing
While urine dipstick testing is widely available, it has significant limitations compared to ACR:
- Lower sensitivity (43.6% for detecting ACR ≥30 mg/g)
- High false-positive rate
- Poor ability to quantify protein levels
- Less accurate prediction of health outcomes 3
Practical Considerations
- When only PCR is available, conversion equations can estimate ACR, though with moderate sensitivity and specificity 4, 5
- ACR and PCR show similar associations with common CKD complications, but ACR is preferred for standardization 6
- Different analytical methods for measuring urinary albumin can affect ACR results, potentially impacting clinical decision-making 7
Conclusion
ACR is the preferred method for assessing albuminuria in CKD screening, diagnosis, and monitoring. It provides valuable information for risk stratification and treatment decisions, with standardized cutoffs that guide clinical management.