Recommended Urine Collection Method for ACR Testing
For ACR testing in patients with diabetes, hypertension, or kidney disease, collect a first morning void spot urine sample and measure the albumin-to-creatinine ratio—this is the preferred method that has replaced 24-hour urine collections in routine clinical practice. 1, 2
Optimal Collection Timing and Technique
- First morning void is the gold standard because it minimizes biological variability from hydration status, exercise, and dietary factors, providing the most accurate and reproducible results 1, 2
- Collect a midstream sample (discard the initial stream) to reduce contamination 2
- If first morning void is difficult to obtain, collect all samples at the same time of day to minimize variability 2
- In children and adolescents, first morning void is particularly important to avoid confounding from orthostatic proteinuria 1
The 2024 KDIGO guidelines and 2003 National Kidney Foundation position statement both explicitly state that timed urine collections should not be used for routine ACR testing 1. The spot urine ACR has replaced 24-hour collections because it eliminates collection errors and speeds clinical decision-making 1.
Critical Pre-Collection Patient Instructions
- Avoid vigorous exercise for 24 hours before collection, as physical activity increases urinary albumin excretion and can cause false elevations 1, 2
- Ensure adequate hydration but no food intake within 2 hours prior to collection 2
- Do not collect during menstruation, as this falsely elevates ACR 2
- Defer testing if the patient has symptomatic urinary tract infection, hematuria, or acute illness—these conditions artificially increase albumin excretion 2
Confirmation Protocol for Abnormal Results
A single elevated ACR is not sufficient for diagnosis. The biological variability of urinary albumin excretion is substantial, with day-to-day changes exceeding 40-50% even in stable patients 2, 3. Therefore:
- Confirm any elevated ACR (≥30 mg/g or ≥3 mg/mmol) with two additional first morning void samples collected over 3-6 months 1, 2
- At least 2 of 3 samples must be abnormal to establish persistent albuminuria and confirm the diagnosis 1, 2
- This confirmation requirement is particularly important because research shows that for patients with microalbuminuria (ACR 30-300 mg/g), a change of ±170% is required to indicate a true change in albuminuria status with 95% certainty 3
Laboratory Handling Standards
The 2024 KDIGO guidelines specify exact handling requirements 1:
- Samples should be analyzed fresh or stored at 4°C for up to 7 days maximum 1, 2
- Do not freeze samples at -20°C, as this compromises albumin measurement accuracy 1, 2
- Laboratories must report ACR (not just albumin concentration alone) to one decimal place, whether in mg/mmol or mg/g 1, 2
- The analytical coefficient of variation for urine albumin methods should be <15% 1
Interpretation Thresholds
The National Kidney Foundation and KDIGO define albuminuria categories as 1:
- Normal: ≤30 mg albumin/g creatinine
- Microalbuminuria (moderately increased): >30 to 300 mg albumin/g creatinine
- Macroalbuminuria (severely increased): >300 mg albumin/g creatinine
Common Pitfalls to Avoid
- Do not use random untimed samples for initial testing unless first morning void is truly unavailable, as these have greater variability 2
- Do not use 24-hour timed urine collections in routine clinical practice—these should be reserved only for special circumstances such as cachexia, muscle atrophy, progressive weight loss, or extreme obesity where creatinine excretion is abnormal 1
- Be aware that biological sex affects interpretation: females have lower urinary creatinine excretion and therefore higher ACR values for the same degree of albuminuria 1, 2
- Recognize that extremes of body weight affect urinary creatinine excretion and can cause falsely low or high ACR relative to actual albumin excretion 1, 2
- Do not rely on dipstick testing alone—immunoassays for albumin with quantitative ACR reporting are required for accurate diagnosis 1
Point-of-Care Testing Considerations
When laboratory access is limited, point-of-care ACR devices may be used, but they must meet strict quality standards 1:
- POCT devices should detect at least 85% of patients with significant albuminuria (ACR ≥30 mg/g or ≥3 mg/mmol) to be considered acceptable 1, 2
- The same pre-analytical, analytical, and post-analytical quality criteria must be applied as with laboratory testing 1
- Recent research demonstrates that ACR strip tests show high sensitivity (80-92%) and specificity (91-94%) in diabetic populations, making them acceptable for screening when quantitative laboratory testing is unavailable 4
Monitoring Frequency
- Test ACR annually in adults with diabetes or hypertension as standard screening 1, 2
- For type 1 diabetes, begin screening 5 years after diagnosis; for type 2 diabetes, begin at diagnosis 2
- Increase monitoring frequency to every 6 months if eGFR is <60 mL/min/1.73 m² or if ACR is ≥30 mg/g 2
- For patients at higher risk of CKD progression, assess more frequently when measurement will impact therapeutic decisions 1