What is the management approach for hematuria with intact versus lysed red blood cells on urinalysis (UA)?

Management Approach for Hematuria with Intact vs Lysed Red Blood Cells on Urinalysis

The presence of dysmorphic (lysed) red blood cells on urinalysis strongly suggests a glomerular source of bleeding requiring nephrology evaluation, while intact (isomorphic) red blood cells typically indicate a non-glomerular urologic source requiring complete urologic evaluation. 1, 2

Determining the Source of Hematuria

Glomerular Source (Lysed/Dysmorphic RBCs)

• Characterized by dysmorphic (irregular, distorted) RBCs (>80% dysmorphic), red cell casts, and significant proteinuria (>500 mg/24 hours) 1
• Dysmorphic RBCs occur due to damage as they pass through inflamed glomeruli 2
• The presence of red cell casts is highly specific for glomerular disease 3
• Combination of proteinuria and hematuria significantly increases likelihood of primary renal disease 3

Non-Glomerular Source (Intact/Isomorphic RBCs)

• Characterized by normal-shaped (isomorphic) RBCs (>80% normal), minimal or no proteinuria (<500 mg/24 hours), and absence of red cell casts 1
• Usually indicates bleeding from the lower urinary tract (bladder, prostate, urethra) or upper collecting system 2
• May be associated with urinary tract infection, stones, tumors, or other urologic conditions 4

Diagnostic Algorithm

Step 1: Initial Assessment

• Exclude benign causes of hematuria (menstruation, vigorous exercise, sexual activity, viral illness, trauma, infection) 1
• Examine urinary sediment for dysmorphic RBCs and red cell casts 1
• Quantify proteinuria with 24-hour urine collection if dipstick shows ≥1+ protein 1
• Measure serum creatinine to assess renal function 1

Step 2: Management Based on RBC Morphology

For Dysmorphic/Lysed RBCs (Glomerular Source):

• Refer to nephrology if there is: 1, 3
  • Proteinuria >1,000 mg/24 hours
  • Proteinuria >500 mg/24 hours that is persistent or increasing
  • Red cell casts
  • Predominantly dysmorphic RBCs
• Nephrology evaluation may include: 1, 3
  • Evaluation for systemic diseases (lupus, vasculitis, infections)
  • Consideration of renal biopsy
  • Assessment of renal function

For Intact/Isomorphic RBCs (Non-Glomerular Source):

• Complete urologic evaluation including: 4, 1, 5
  • History and physical examination
  • Radiologic imaging of upper urinary tract (CT urography preferred)
  • Cystoscopic examination of urinary bladder
• Refer to urology if there is: 1, 5
  • Age >40 years
  • Smoking history
  • History of gross hematuria
  • Occupational exposure to chemicals or dyes
  • Previous urologic disorder
  • Irritative voiding symptoms
  • Recurrent urinary tract infections

Important Clinical Considerations

• Even with predominantly dysmorphic RBCs (≥40%), urologic evaluation should not be omitted as studies show 34% of such patients may have urologic disease, including malignancies requiring treatment 6
• The presence of proteinuria has higher diagnostic value for predicting glomerular disease than RBC morphology alone 6
• For patients with persistent hematuria after negative initial evaluation, repeat urinalysis at 6,12,24, and 36 months 1, 5
• Do not attribute hematuria solely to anticoagulation therapy, BPH, or other common conditions without proper evaluation 3, 5
• In women, obtain a catheterized specimen if clean-catch cannot be reliably obtained due to vaginal contamination 4, 1

Technical Considerations for RBC Morphology Assessment

• Scanning electron microscopy shows marked differences between dysmorphic and isomorphic RBCs, but standard light microscopy can be used in clinical practice 7
• Coulter counter analysis has shown 97% accuracy in differentiating glomerular versus non-glomerular hematuria 7
• The degree of hematuria is a significant risk factor, with >25 RBC/HPF indicating high risk for urologic pathology 5