Why Creatinine is Used in the Albumin-to-Creatinine Ratio (ACR)
Creatinine is used in the albumin-to-creatinine ratio because it provides a convenient and accurate way to normalize albumin excretion for variations in urine concentration, eliminating the need for inconvenient and error-prone timed urine collections. 1
Primary Functions of Creatinine in ACR
Normalizes for urine concentration: Creatinine corrects for variations in urinary albumin concentration due to hydration status, making the measurement more reliable regardless of how dilute or concentrated the urine sample is 1, 2
Eliminates need for timed collections: The ratio of albumin to creatinine in an untimed urine sample provides an accurate estimate of albumin excretion rate without requiring inconvenient 24-hour urine collections 1
Improves test reliability: Using the albumin-to-creatinine ratio in a first morning void sample results in the lowest coefficient of variation (31%) compared to other methods of measuring albumin excretion 1
Clinical Advantages of Using ACR
Better prediction of outcomes: The albumin-to-creatinine ratio is the best method to predict renal events in people with type 2 diabetes 1
Strong correlation with gold standard: The ratio correlates well with both timed excretion and albumin concentration in first morning void urine samples 1
Improved screening utility: Using creatinine in the ratio allows for standardized screening across different populations and improves clinical interpretation 3
High agreement with 24-hour collections: Studies show 88% agreement between ACR in early morning void and 24-hour urinary albumin excretion categories 4
Practical Implementation of ACR
Preferred sample type: First morning void urine sample should be used for measurement of albumin-to-creatinine ratio to minimize variability 1
Standardized collection: To further minimize variability, collections should be at the same time of day, and the person should not have ingested food for at least 2 hours prior to collection 1
Reporting standards: ACR results are typically categorized as:
- Normal: <30 mg/g
- Moderately increased (formerly microalbuminuria): 30-299 mg/g
- Severely increased: >300 mg/g 5
Limitations and Considerations
Sex-specific differences: Some studies suggest sex-specific cutoff values for ACR (>17 mg/g in men or >25 mg/g in women) due to differences in creatinine excretion 1
Interindividual variation: Creatinine excretion can vary based on age, sex, ethnicity, and muscle mass, which may affect interpretation of ACR results 2
Analytical variability: Considerable intermethod differences have been reported for both albumin and creatinine measurement, highlighting the need for standardization 2
Clinical Decision Making with ACR
Confirmation of results: Elevated ACR should be confirmed with 2 additional tests during the subsequent 3-6 months due to high day-to-day variability 6
Monitoring frequency: For patients with moderately increased albuminuria (ACR 30-299 mg/g), monitor ACR and eGFR at least annually 6
Risk assessment: At any level of GFR, increased ACR is associated with higher risk for adverse outcomes, and the risk increases as ACR rises 5
By using creatinine to normalize albumin excretion, clinicians can more accurately assess kidney damage, predict disease progression, and monitor treatment response with a simple, convenient urine test that doesn't require timed collections.