How Dipstick Works

Reagent Pads on Standard Dipstick:

Timing and Storage

• Read at correct time: Usually 60 seconds (varies by manufacturer)
• Exposure to light: Degrades reagents
• Temperature: Cold urine may give false negatives
• Air exposure: Nitrites and leukocyte esterase degrade
• Refrigeration: Prolongs accuracy; room temperature deteriorates within 2 hours

Dipstick Proteinuria Interpretation

Dipstick Grading: - Negative: <10 mg/dL - Trace: 10-15 mg/dL - 1+: 30 mg/dL - 2+: 100 mg/dL - 3+: 300 mg/dL - 4+: ≥1000 mg/dL (nephrotic-range)

Critical Limitations of Dipstick

False Positives (positive dipstick with low actual protein): 1. Concentrated urine (high specific gravity, dehydration) 2. Alkaline urine (pH >7; dipstick more sensitive in alkaline conditions) 3. Gross hematuria (hemoglobin itself positive with dipstick) 4. Contaminating blood (even from traumatic catheterization) 5. Quaternary ammonium compounds (residual antiseptic on collection containers) 6. Contrast agents (from recent imaging)

False Negatives (negative dipstick with actual proteinuria): 1. Bence Jones proteins (immunoglobulin light chains; multiple myeloma) - Dipstick primarily detects albumin - Light chain proteins may not react - Require specialized tests (serum/urine protein electrophoresis, free light chains)

2. Myoglobin (rhabdomyolysis)
   • Small molecular weight
   • May be missed or underestimated by dipstick
3. Dilute urine (excessive hydration)
   • Protein concentration too low to trigger dipstick

Quantifying Proteinuria

When to use QUANTITATIVE measures: - Dipstick ≥1+ (significant) - Ongoing monitoring needed - Nephrotic syndrome workup - CKD monitoring

Available Tests:

Interpreting Spot ACR/PCR:

Dipstick Blood/RBC Interpretation

Dipstick Blood Positive Indicates: - RBCs - Hemoglobin (from lysed RBCs) - Myoglobin (muscle breakdown) - ⚠️ Cannot distinguish between them

Microscopy Differentiation

With RBCs on microscopy (dysmorphic): - True hematuria (from kidney or urinary tract) - If RBC casts present → glomerulonephritis (RPGN, IgAN, etc.)

Without RBCs on microscopy (dipstick positive): - Hemoglobinuria (intravascular hemolysis) - Myoglobinuria (rhabdomyolysis) - False positive (from other causes below)

False Positives for Hematuria

Cause 1: Contaminating Blood - Traumatic catheterization - Menses in women - Hematospermia in men - Management: Repeat clean-catch specimen; wait 48 hours if traumatic catheterization

Cause 2: Pigmenturia (Hemoglobin-Like) - Hemoglobinuria (intravascular hemolysis) - Severe hemolysis → hemoglobin exceeds renal reabsorption capacity - Dipstick positive; no RBCs on microscopy - Management: Check free plasma hemoglobin, LDH, bilirubin, reticulocyte count

• Myoglobinuria (rhabdomyolysis)
  • Muscle breakdown releases myoglobin
  • Dipstick positive; no RBCs on microscopy
  • Associated with CK elevation, brown urine color
  • Management: Check CK, urine myoglobin, creatinine (AKI risk)

Cause 3: Oxidizing Agents - Hydrogen peroxide contamination - Bleach exposure - Rare but documented

Clinical Approach to Hematuria

Step 1: Microscopy - RBCs present? (True hematuria) - RBC casts? (Glomerulonephritis) - No RBCs? (Hemoglobinuria or myoglobinuria)

Step 2: Additional Tests if Needed - Free plasma hemoglobin (hemolysis) - Creatine kinase (rhabdomyolysis) - LDH, bilirubin, reticulocyte count (hemolysis workup) - Urine myoglobin (rhabdomyolysis)

Step 3: Clinical Context - Dysmorphic RBCs + RBC casts = Glomerulonephritis (biopsy candidate) - Isomorphic RBCs without casts = Lower urinary tract source (cystitis, stone, malignancy) - No RBCs + positive dipstick = Hemoglobinuria or myoglobinuria (investigate cause)

Cells in Urine

Casts

What are Casts? - Cylindrical protein precipitates formed in collecting duct - Composed of Tamm-Horsfall protein (uromodulin) + cellular inclusions - Always abnormal (except rare hyaline in concentrated urine)

Crystals

Microorganisms

Bacteria: - None: Normal - Few: Likely contamination - Numerous (>5/lpf): Suggests UTI; quantify with culture

Yeast (Candida): - Vaginal contamination (women) - True candiduria (catheters, immunocompromised) - Usually not clinically significant unless symptoms present

Orthostatic Proteinuria

Definition: Protein present in daytime urine but absent in overnight urine

Characteristics: - More common in young, tall, thin males (5-15%) - Completely benign; excellent long-term prognosis - Due to postural changes and increased capillary pressure upright

Diagnosis: - Split collection: daytime vs. overnight urine - Daytime shows protein; overnight shows none - Can follow up with repeat spot urine in morning

Clinical Pearl: If orthostatic proteinuria diagnosed, reassure patient and no further workup needed

Transient Proteinuria

Causes: - Fever - Stress - Seizures - Extreme exercise (marathon running → can reach nephrotic levels) - Vigorous physical activity

Management: - Repeat testing when patient returns to baseline - Usually resolves within 24-48 hours

Contamination Issues

Signs of Contamination: - Numerous squamous epithelial cells (>5/lpf) = improperly collected specimen - Numerous bacteria without pyuria = likely contamination - RBCs + bacteria in female = consider menses as source

Proper Collection: - Women: Cleanse urethral meatus; midstream catch - Men: Retract foreskin; midstream catch - Avoid external contamination

When to Culture

Send Culture When: - Pyuria (WBC >5/lpf) + symptoms of UTI - Hematuria + pyuria (rule out infection) - Fever + lower abdominal pain - Pyelonephritis symptoms (fever, flank pain, CVA tenderness) - Catheterized patients with symptoms - Asymptomatic bacteriuria (only in pregnancy, pre-urologic procedures)

Do NOT Culture: - Asymptomatic bacteriuria (except pregnancy) - Pyuria without symptoms (low positive predictive value) - Prophylactic culture in non-pregnant, non-procedure patients

Interpreting Culture Results