Range of Proteinuria
Normal urinary protein excretion is less than 150 mg per 24 hours (or a spot protein-to-creatinine ratio <200 mg/g), microalbuminuria ranges from 30–299 mg per 24 hours (30–299 mg/g on spot collection), overt proteinuria begins at 300 mg per 24 hours (≥300 mg/g), and nephrotic-range proteinuria is defined as ≥3.5 g per 24 hours (≥3,500 mg/g). 1, 2, 3, 4
Normal Range
- Urinary protein excretion below 150 mg per 24 hours is considered normal, with many laboratories using an even stricter cutoff of 40–100 mg per day for completely normal values. 5
- When expressed as a spot urine protein-to-creatinine ratio (UPCR), normal is defined as <200 mg/g (0.2 mg/mg). 2, 3, 6
- For albumin-specific measurements (albumin-to-creatinine ratio, ACR), normal is <30 mg/g. 1, 2
Microalbuminuria (Moderately Increased Albuminuria)
- Microalbuminuria is defined as urinary albumin excretion of 30–299 mg per 24 hours, which corresponds to an ACR of 30–299 mg/g on a spot collection or 20–199 µg/min on a timed specimen. 1
- This range represents early glomerular injury, particularly important in diabetic patients where it signals the onset of diabetic nephropathy. 1
- Two of three specimens collected within a 3- to 6-month period should be abnormal before confirming that a patient has crossed into the microalbuminuria range, because day-to-day variability in albumin excretion is substantial. 1, 2
Overt Proteinuria (Clinical Albuminuria / Macroalbuminuria)
- Overt proteinuria begins at 300 mg per 24 hours (≥300 mg/g on spot UPCR or ≥200 µg/min on timed collection). 1, 2
- In diabetic patients, this threshold marks the transition from microalbuminuria to clinical albuminuria (macroalbuminuria), indicating established diabetic nephropathy. 1, 2
- Moderate proteinuria is typically defined as 1–3 g per day (UPCR 1,000–3,000 mg/g), which warrants nephrology evaluation because it likely reflects glomerular disease. 2
Nephrotic-Range Proteinuria
- Nephrotic-range proteinuria is classically defined as ≥3.5 g per 24 hours (UPCR ≥3,500 mg/g or ≥3.5 mg/mg). 2, 3, 4
- When expressed as a spot ratio, a UPCR >3.5 mg/mg (or >3,500 mg/g) represents nephrotic-range proteinuria. 3
- This level of proteinuria is associated with nephrotic syndrome, which includes hypoalbuminemia (<30 g/L), edema, hyperlipidemia, and increased risk of thromboembolism and infection. 4
- Immediate nephrology referral is mandatory for nephrotic-range proteinuria because it carries high risk for progressive kidney disease, cardiovascular events, and typically requires kidney biopsy to determine the underlying cause and guide immunosuppressive therapy. 2
Practical Measurement Considerations
- Spot urine protein-to-creatinine ratio (UPCR) has replaced 24-hour collections for routine screening and monitoring because it eliminates collection difficulties, provides rapid results, and correlates excellently (r=0.96–0.97) with 24-hour protein excretion. 2, 3, 6, 7
- First-morning void specimens are preferred to minimize variability and exclude orthostatic proteinuria, though random daytime specimens are acceptable for adults. 2
- Transient elevations occur with exercise within 24 hours, infection, fever, congestive heart failure, marked hyperglycemia, marked hypertension, pyuria, and hematuria, so these conditions should be excluded before confirming persistent proteinuria. 1, 2
Common Pitfalls
- Do not diagnose chronic kidney disease based on a single elevated result; persistence must be confirmed with repeat testing over 3 months. 1, 2
- Dipstick testing measures protein concentration (mg/dL), not total excretion, making results highly dependent on urine concentration and unsuitable for accurate quantification—always confirm with quantitative UPCR or ACR. 2, 5
- In patients with concurrent liver disease or reduced albumin synthesis, nephrotic syndrome may occur with proteinuria below the 3.5 g/day threshold because the steady state is reached at lower protein excretion despite severe glomerular permeability defects. 8
- Reserve 24-hour urine collections for specific indications only: confirming nephrotic-range proteinuria for thromboprophylaxis decisions, establishing baseline before immunosuppression in glomerular disease, or evaluating patients with extreme body habitus where creatinine excretion is abnormal. 2