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Quick Reference
  • Normal Range (Dipstick): Negative (<10 mg/dL)
  • Normal Range (24-hour): <150 mg/day
  • Microalbuminuria: 30-300 mg/day
  • Nephrotic Range: >3.5 g/day
  • Protein-to-Creatinine Ratio: <0.2 mg/mg (normal)
  • Primary Use: Screening for kidney disease, glomerular disorders, and systemic conditions affecting the kidney
  • Sample Type: Random urine (dipstick), spot urine (protein-to-creatinine ratio), or 24-hour urine collection
  • Key Point: Dipstick primarily detects albumin and may miss non-albumin proteins like Bence Jones protein

Test Description

Urine protein testing measures the amount of protein excreted in the urine, which is normally minimal. The glomerular filtration barrier prevents most proteins from entering the urine, and small amounts that do pass through are typically reabsorbed by the renal tubules. Proteinuria indicates either increased glomerular permeability, decreased tubular reabsorption, or overflow of abnormal proteins.

Proteinuria is a key marker of kidney disease and is associated with cardiovascular risk and progression to end-stage renal disease. Persistent proteinuria warrants further investigation to identify the underlying cause and guide treatment decisions.

Methods of Protein Detection

  • Urine Dipstick: Semi-quantitative screening test that detects primarily albumin (not sensitive to light chains or other non-albumin proteins)
  • Protein-to-Creatinine Ratio (UPCR): Spot urine test that estimates 24-hour protein excretion; more convenient and correlates well with 24-hour collection
  • 24-Hour Urine Collection: Gold standard for quantifying total protein excretion, though less convenient and prone to collection errors
  • Albumin-to-Creatinine Ratio (ACR): Preferred for detecting microalbuminuria in diabetic nephropathy screening
Normal Ranges

Protein excretion varies by method of collection and can be classified into different categories based on the amount and clinical significance.

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Test Method Normal Range Clinical Significance
Dipstick (Random Urine) Negative (<10 mg/dL) Screening test
24-Hour Urine Protein <150 mg/day Quantitative measurement
Protein-to-Creatinine Ratio <0.2 mg/mg (or <200 mg/g) Spot urine estimation
Albumin-to-Creatinine Ratio <30 mg/g Microalbuminuria screening

Classification of Proteinuria

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Category 24-Hour Protein UPCR (mg/mg) Clinical Context
Normal <150 mg/day <0.2 No significant proteinuria
Microalbuminuria 30-300 mg/day 0.03-0.3 Early diabetic nephropathy
Clinical Proteinuria 150-3,500 mg/day 0.2-3.5 Glomerular disease, tubulointerstitial disease
Nephrotic Range >3,500 mg/day >3.5 Nephrotic syndrome
Important Considerations:
  • Dipstick results can be affected by urine concentration (specific gravity)
  • Dipstick primarily detects albumin; may miss Bence Jones protein (light chains) seen in multiple myeloma
  • Protein-to-creatinine ratio approximates 24-hour protein (ratio of 1.0 ≈ 1 g/day)
  • Transient proteinuria can occur with fever, exercise, dehydration, or stress
Clinical Significance

Causes of Proteinuria

Glomerular Proteinuria (Most Common)

  • Diabetic Nephropathy: Leading cause of nephrotic syndrome; begins with microalbuminuria progressing to overt proteinuria
  • Glomerulonephritis: IgA nephropathy, membranous nephropathy, focal segmental glomerulosclerosis (FSGS), minimal change disease
  • Hypertensive Nephrosclerosis: Chronic hypertension leading to glomerular damage
  • Preeclampsia: New-onset proteinuria after 20 weeks gestation (protein-to-creatinine ratio >0.3 mg/mg)
  • Lupus Nephritis: Systemic lupus erythematosus with renal involvement
  • Amyloidosis: Deposition of abnormal proteins in glomeruli

Tubular Proteinuria

  • Acute Tubular Necrosis (ATN): Impaired tubular reabsorption of filtered proteins
  • Tubulointerstitial Nephritis: Drug-induced or autoimmune tubular damage
  • Fanconi Syndrome: Generalized proximal tubule dysfunction

Overflow Proteinuria

  • Multiple Myeloma: Bence Jones protein (immunoglobulin light chains) not detected by standard dipstick
  • Myoglobinuria: Rhabdomyolysis with muscle breakdown
  • Hemoglobinuria: Intravascular hemolysis

Functional/Transient Proteinuria

  • Orthostatic Proteinuria: Benign condition in adolescents/young adults; protein only present when upright
  • Exercise-Induced: Resolves with rest
  • Fever/Acute Illness: Temporary increase during acute stress

Nephrotic vs Nephritic Syndrome

Nephrotic Syndrome (Heavy Proteinuria)
- Proteinuria >3.5 g/day (nephrotic range)
- Hypoalbuminemia (<3 g/dL)
- Edema (peripheral, periorbital)
- Hyperlipidemia
- Causes: Minimal change disease, FSGS, membranous nephropathy, diabetic nephropathy
Nephritic Syndrome (Glomerular Inflammation)
- Hematuria with RBC casts
- Hypertension
- Proteinuria (sub-nephrotic to nephrotic range)
- Edema and oliguria
- Causes: Post-streptococcal GN, IgA nephropathy, lupus nephritis, rapidly progressive GN
Interpretation Guidelines

Dipstick Protein Grading

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Dipstick Result Approximate Protein (mg/dL) Interpretation
Negative <10 Normal
Trace 10-20 Borderline; repeat if persistent
1+ 30 Mild proteinuria
2+ 100 Moderate proteinuria
3+ 300 Heavy proteinuria
4+ >2,000 Severe proteinuria (likely nephrotic)

Workup of Persistent Proteinuria

  1. Confirm Persistence: Repeat urinalysis on first morning void (eliminates orthostatic proteinuria)
  2. Quantify Proteinuria: Obtain spot urine protein-to-creatinine ratio or 24-hour urine collection
  3. Assess for Albuminuria: Albumin-to-creatinine ratio if concerned for diabetic nephropathy
  4. Evaluate for Systemic Disease: Serum creatinine, eGFR, urinalysis with microscopy, blood glucose, lipid panel
  5. Consider Renal Biopsy: For unexplained proteinuria >1 g/day or nephrotic-range proteinuria
Protein-to-Creatinine Ratio Interpretation
UPCR (mg/mg) approximates 24-hour protein excretion in grams
- UPCR 0.5 ≈ 0.5 g/day protein
- UPCR 3.5 ≈ 3.5 g/day protein (nephrotic range)
- UPCR >3.5 indicates nephrotic-range proteinuria
Interfering Factors

False Positive Results (Dipstick)

  • Concentrated Urine: Low specific gravity can cause false trace results; high specific gravity can intensify results
  • Alkaline Urine: pH >8 (contamination with quaternary ammonium compounds, old urine)
  • Gross Hematuria: Red blood cells can cause false positive protein
  • Pyuria (WBCs): Heavy leukocyturia may cause trace positive
  • Antiseptics: Chlorhexidine, benzalkonium chloride contamination
  • Contrast Dye: Recent radiologic contrast administration

False Negative Results (Dipstick)

  • Dilute Urine: Specific gravity <1.010 may dilute protein below detection threshold
  • Non-Albumin Proteins: Bence Jones protein (immunoglobulin light chains) not detected by standard dipstick
  • Acidic Urine: Very acidic urine may reduce dipstick sensitivity
  • Microalbuminuria: Standard dipstick not sensitive enough; requires albumin-specific testing

Medications Affecting Protein Levels

Increase Proteinuria

  • NSAIDs: Can cause membranous nephropathy or interstitial nephritis
  • ACE Inhibitors/ARBs: May initially increase proteinuria before reduction (monitor closely)
  • Lithium: Chronic use can cause tubulointerstitial disease
  • Gold, Penicillamine: Membranous nephropathy

Decrease Proteinuria

  • ACE Inhibitors/ARBs: Reduce proteinuria in chronic kidney disease (therapeutic effect)
  • SGLT2 Inhibitors: Reduce albuminuria in diabetic nephropathy

Collection Issues

  • 24-Hour Collection Errors: Incomplete collection, missed voids, improper timing
  • Contamination: Vaginal secretions, semen, menstrual blood
  • Prolonged Standing: Urine specimens left at room temperature may degrade
Clinical Pearls
Clinical Pearl
"Dipstick doesn't detect Bence Jones protein": In suspected multiple myeloma, a negative dipstick does NOT rule out proteinuria. Must perform urine protein electrophoresis (UPEP) or immunofixation to detect monoclonal light chains.
Clinical Pearl
Orthostatic Proteinuria: Common benign finding in adolescents and young adults. Test first morning void (supine) - if negative, confirms orthostatic proteinuria and no further workup needed. Protein only appears when upright.
Clinical Pearl
Spot UPCR vs 24-Hour Collection: Spot urine protein-to-creatinine ratio is much more convenient and correlates well with 24-hour urine protein. UPCR value approximates grams of protein per day (e.g., UPCR 2.0 ≈ 2 g/day).
Clinical Pearl
Microalbuminuria Screening: Annual screening recommended for diabetic patients (Type 1 after 5 years; Type 2 at diagnosis). Early detection allows for ACE inhibitor/ARB therapy to slow progression to overt nephropathy.
Nephrotic vs Nephritic Differentiation:
Nephrotic: Massive proteinuria (>3.5 g/day), edema, hypoalbuminemia, hyperlipidemia
Nephritic: Hematuria with RBC casts, hypertension, mild-moderate proteinuria, acute kidney injury
Preeclampsia Diagnosis: Protein-to-creatinine ratio >0.3 mg/mg (or >300 mg/24 hours) after 20 weeks gestation with new-onset hypertension. Dipstick alone not reliable for preeclampsia diagnosis.
Clinical Pearl
Transient Proteinuria: Can occur with fever, intense exercise, dehydration, heart failure, or emotional stress. Always repeat urinalysis when patient is well-hydrated and afebrile before pursuing extensive workup.
Clinical Pearl
ACE Inhibitor Effect: May see initial slight increase in proteinuria when starting ACE inhibitor or ARB, but long-term effect is reduction in proteinuria and renoprotection. Don't stop medication based on early increase alone.
Red Flag for Immediate Evaluation: Nephrotic-range proteinuria (>3.5 g/day) with edema, hypertension, or acute kidney injury requires urgent nephrology referral. May need immunosuppression or specific therapy.
Complement Urinalysis with Microscopy: Always examine urine sediment when proteinuria is detected. RBC casts suggest glomerulonephritis; WBC casts suggest pyelonephritis or interstitial nephritis; fatty casts/oval fat bodies suggest nephrotic syndrome.
References
  1. Kratz, A., Ferraro, M., Sluss, P. M., & Lewandrowski, K. B. (2004). Laboratory reference values. New England Journal of Medicine, 351, 1548-1564.
  2. Lee, M. (Ed.). (2009). Basic skills in interpreting laboratory data. Ashp.
  3. Farinde, A. (2021). Lab values, normal adult: Laboratory reference ranges in healthy adults. Medscape. https://emedicine.medscape.com/article/2172316-overview?form=fpf
  4. Nickson, C. (n.d.). Critical Care Compendium. Life in the Fast Lane • LITFL. https://litfl.com/ccc-critical-care-compendium/
  5. Farkas, Josh MD. (2015). Table of Contents - EMCrit Project. EMCrit Project. https://emcrit.org/ibcc/toc/
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