What the Albumin-to-Creatinine Ratio Indicates
An elevated urine albumin-to-creatinine ratio (UACR) indicates kidney damage, specifically increased permeability of the glomerular filtration barrier allowing albumin to leak into urine, and serves as both a diagnostic marker for chronic kidney disease and a powerful predictor of cardiovascular events and mortality. 1
Why Creatinine is Used in the Ratio
The albumin-to-creatinine ratio normalizes albumin excretion for variations in urine concentration, eliminating the need for inconvenient 24-hour urine collections. 2 Measuring albumin alone without simultaneously measuring creatinine is susceptible to false-negative and false-positive results due to hydration-related changes in urine concentration. 1, 2
Using creatinine as the denominator provides a convenient and accurate way to estimate albumin excretion rate from a single spot urine sample. 2 The ratio correlates well with timed excretion measurements and demonstrates the lowest coefficient of variation (31%) when obtained from first morning void samples. 2
Clinical Significance of Elevated UACR
Classification Categories
- Normal: UACR <30 mg/g creatinine 1, 3
- Moderately increased albuminuria (A2): UACR 30-299 mg/g creatinine 1, 3
- Severely increased albuminuria (A3): UACR ≥300 mg/g creatinine 1, 3
What Elevation Indicates
UACR is a continuous measurement where even differences within the normal and abnormal ranges are associated with renal and cardiovascular outcomes. 1, 2 Higher UACR within the normal range (<30 mg/g) is associated with increased all-cause and cardiovascular mortality risk. 4 Research demonstrates that UACR >10 mg/g in diabetic patients significantly predicts cumulative incidence and progression of CKD. 5
In diabetic kidney disease, elevated UACR typically develops after 10+ years duration in type 1 diabetes but may be present at diagnosis in type 2 diabetes. 1, 2 The presence of CKD (indicated by elevated UACR and/or reduced eGFR) markedly increases cardiovascular risk and healthcare costs. 1
Diagnostic Approach
Confirmation Requirements
Due to high biological variability exceeding 20% between measurements, two of three specimens collected within a 3-6 month period should be abnormal before confirming persistent albuminuria. 1, 2 A recent study quantified within-individual variability at 48.8%, showing a repeated UACR could be as high as 3.78 times or as low as 0.26 times the first measurement. 6
Factors Causing False Elevation
Exclude these transient conditions before confirming chronic elevation: 2, 3
- Exercise within 24 hours
- Active urinary tract infection or fever
- Congestive heart failure exacerbation
- Marked hyperglycemia
- Menstruation
- Marked uncontrolled hypertension
Optimal Collection Method
First morning void urine samples are preferred to minimize variability. 2, 3 Spot urine samples for UACR are superior to timed or 24-hour collections, which are more burdensome and add little to prediction or accuracy. 1, 2
Risk Stratification and Prognosis
At any level of GFR, increased UACR is associated with higher risk for adverse outcomes, and the risk increases continuously as UACR rises. 2 A 2025 meta-analysis of 148,994 participants demonstrated that UACR exhibits stronger associations with kidney failure (adjusted HR per SD increment: 2.55) compared to total protein-to-creatinine ratio (HR: 2.40). 7
UACR is the best method to predict renal events in people with type 2 diabetes. 2 The association between UACR and kidney failure is particularly strong in subgroups with UACR >30 mg/g, eGFR <60 mL/min/1.73 m², diabetes, and glomerular disease. 7
Management Implications
When UACR is 30-299 mg/g (Moderately Increased)
Initiate ACE inhibitor or ARB therapy immediately, regardless of baseline blood pressure, for specific antiproteinuric effects beyond blood pressure lowering. 1, 2 Target blood pressure <130/80 mmHg. 1, 2
Monitoring frequency based on eGFR: 2
- eGFR ≥60: Monitor ACR and eGFR annually
- eGFR 45-59: Monitor every 6 months
- eGFR 30-44: Monitor every 3-4 months
- eGFR <30: Immediate nephrology referral
When UACR is ≥300 mg/g (Severely Increased)
This indicates advanced kidney damage with very high cardiovascular and progression risk. 2 Monitor ACR and eGFR every 6 months if eGFR >60, and every 3 months if eGFR 30-60. 2 Consider immediate nephrology referral for persistent elevation. 2
Treatment Goals
Aim for at least 30-50% sustained reduction in albuminuria, ideally achieving UACR <30 mg/g. 2, 3 Sustained reduction in albuminuria is a validated surrogate for slowed CKD progression. 2
Common Pitfalls
Do not rely on a single UACR measurement for clinical decision-making due to high day-to-day variability. 6 Single measurements can have up to 40-50% variability. 3 If a single-collection UACR increased from 2 to 5 mg/mmol, the probability that UACR actually increased by at least 30% is only 50%, rising to 97% when 2 collections are obtained at each time point. 6
Do not measure albumin alone without creatinine, as this is susceptible to false results from hydration changes. 1, 3 Avoid 24-hour timed collections for routine screening; spot UACR provides equivalent clinical information with better patient compliance. 3