What is the protein‑creatinine ratio?

What is the Protein-Creatinine Ratio?

The protein-creatinine ratio (PCR) is a laboratory test that measures the concentration of protein relative to creatinine in a spot (random or first-morning) urine sample, correcting for variations in urinary concentration due to hydration status, and serves as the preferred method for detecting and monitoring proteinuria as a marker of kidney damage. 1, 2

How the Test Works

• PCR measures total urinary protein (including albumin, tubular proteins, immunoglobulins, and other plasma proteins) indexed to urine creatinine concentration to account for urinary dilution or concentration 2
• The ratio is calculated by dividing urine protein concentration (mg/L) by urine creatinine concentration (mg/L or mmol/L), typically reported as mg protein per gram creatinine (mg/g) 1, 3
• This spot urine measurement eliminates the need for cumbersome 24-hour urine collections while providing comparable accuracy 1, 4

Normal and Abnormal Values

• Normal PCR is <200 mg/g (<0.2 mg/mg or <20 mg/mmol) in the general adult population 1, 3
• In pregnancy, the threshold is higher: <300 mg/g (<0.3 mg/mg or <30 mg/mmol) is considered normal 1, 3
• Moderate proteinuria is defined as PCR 1,000-3,000 mg/g (1-3 g/g), warranting nephrology evaluation 1
• Nephrotic-range proteinuria is PCR >3,500 mg/g (>3.5 g/g), requiring immediate nephrology referral 1, 3

Clinical Interpretation Categories

The KDIGO guidelines stratify PCR into three risk categories 2:

• Normal: <150 mg/g
• Moderately Increased: 150-499 mg/g
• Severely Increased: ≥500 mg/g

PCR vs Albumin-Creatinine Ratio (ACR)

• ACR is preferred over PCR for most clinical situations because it can be standardized using immunochemical techniques, is more accurate in the lower range of protein excretion, and is more sensitive for detecting early kidney damage 2
• ACR measures only albumin (the predominant filtered protein), while PCR measures total protein 2
• PCR may be useful when non-albumin proteinuria is suspected, such as in tubular disorders, tubulointerstitial disease, or paraprotein disorders (e.g., multiple myeloma) 2
• For diabetic kidney disease screening and early CKD detection, ACR is the recommended test 2

Sample Collection Best Practices

• First morning void is preferred because it correlates best with 24-hour protein excretion, has low intra-individual variability, and avoids orthostatic proteinuria 1, 2, 5
• Random daytime specimens are acceptable for adults in most clinical scenarios, though they show more variability 1
• Avoid vigorous exercise for 24 hours before collection, as physical activity causes transient proteinuria elevation 1, 6
• Avoid collection during menses due to contamination risk 1
• Samples should be refrigerated and analyzed within 24 hours 2

Correlation with 24-Hour Urine Collection

• Multiple studies demonstrate excellent correlation (r=0.83-0.96) between spot urine PCR and 24-hour urine protein excretion 5, 7, 4, 8
• PCR values essentially equal 24-hour protein excretion in grams per day (e.g., PCR of 1.2 mg/mg approximates 1.2 g/24h) 7, 4
• The correlation is strongest when proteinuria is at reasonably low levels (<2 g/day); limits of agreement widen as protein excretion increases 7
• For patients with creatinine clearance ≤10 mL/min, correlation may not be significant 5

When to Confirm with Repeat Testing

• Always confirm an elevated PCR with repeat testing within 3 months before making definitive diagnosis or treatment decisions, as transient proteinuria is common 1, 2, 6
• Persistent proteinuria is defined as 2 of 3 positive samples over 3 months 1
• Transient causes of false elevation include urinary tract infection, fever, acute illness, vigorous exercise, orthostatic proteinuria, marked hyperglycemia, marked hypertension, and congestive heart failure 1, 2, 6

When 24-Hour Collection is Still Needed

Despite PCR's convenience, 24-hour urine collection remains necessary in specific situations 1:

• Confirming nephrotic syndrome (>3.5 g/day) for thromboprophylaxis decisions
• Patients with glomerular disease requiring initiation or intensification of immunosuppression, where precise baseline measurement guides treatment
• Patients with extremes of body habitus (cachexia, muscle atrophy, extreme obesity) where creatinine excretion is abnormal
• Simultaneous measurement of creatinine clearance when GFR estimation equations are unreliable

Common Pitfalls to Avoid

• Do not rely on a single dipstick or PCR reading without quantitative confirmation and repeat testing 1
• Do not ignore the clinical context: muscle mass, age, sex, and race affect creatinine excretion and thus the denominator of the ratio 2
• When monitoring individual patients over time, collect samples at the same time of day with similar activity levels to ensure accurate trend assessment 1, 6
• Absolute creatinine level on random urine is meaningless without context; only the protein-to-creatinine ratio matters 1
• Starting collection with the first morning void instead of discarding it, or failing to include the final void in 24-hour collections, leads to inaccurate results 1