What are the guidelines for working up microhematuria (presence of microscopic blood in urine)?

Guidelines for Working Up Microhematuria

Patients with microhematuria should be classified based on their risk of genitourinary malignancy and evaluated with a risk-based diagnostic strategy that includes cystoscopy and upper tract imaging for those at intermediate or high risk. 1

Definition of Microhematuria

• Microhematuria is defined as ≥3 red blood cells per high-power field (RBC/HPF) on microscopic evaluation of a single properly collected urine specimen 1
• Previous guidelines recommended confirmation with 2 of 3 properly collected specimens 1, but the 2020 AUA guideline simplified this to a single specimen

Initial Evaluation

Step 1: Exclude Benign Causes

• Rule out benign causes including:
  • Menstruation
  • Vigorous exercise
  • Sexual activity
  • Viral illness
  • Trauma
  • Urinary tract infection 1
• If a benign cause is identified, repeat urinalysis 48 hours after resolution of the potential cause 1
• For patients with UTI, treat appropriately and repeat urinalysis 6 weeks after treatment 1

Step 2: Risk Stratification

Classify patients into risk categories for genitourinary malignancy:

High-Risk Factors:

• Age >40 years
• Smoking history
• Gross hematuria (even if resolved)
• Male sex
• Occupational exposure to chemicals or dyes (benzenes or aromatic amines)
• History of urologic disorder or disease
• History of irritative voiding symptoms
• History of recurrent UTI despite appropriate antibiotic use
• History of pelvic irradiation
• Analgesic abuse 1

Step 3: Evaluate for Renal Parenchymal Disease

If any of the following are present, evaluate for primary renal disease:

• Significant proteinuria (≥1+ on dipstick)
• Dysmorphic red blood cells or red cell casts
• Elevated serum creatinine level 1

Diagnostic Algorithm

For Suspected Renal Disease:

• Nephrology referral
• Consider renal biopsy if systemic causes are not identified 1
• 24-hour urine collection to quantitate proteinuria (if >1g/day, thorough evaluation or nephrology referral is recommended) 1

For Urologic Evaluation:

1. Laboratory Analysis:

   • Complete urinalysis with microscopic examination
   • Serum creatinine
   • Urine culture if infection suspected

2. Urinary Cytology:

   • Recommended for all patients with risk factors for transitional cell carcinoma 1
   • Limited utility in initial evaluation of microhematuria due to low sensitivity 2

3. Upper Tract Imaging:

   • CT Urography (CTU) is the preferred imaging modality for high-risk patients
     • Includes unenhanced images followed by nephrographic and excretory phases 1
   • Ultrasound may be appropriate for low-risk patients or those who cannot undergo CT 1
   • MR Urography can be considered in patients who cannot receive iodinated contrast 1

4. Cystoscopy:

   • Recommended for all patients at intermediate or high risk 1
   • Can be deferred in low-risk patients with a negative upper tract evaluation 1

Risk-Based Evaluation Strategy

Low-Risk Patients:

• Age <40 years
• No risk factors
• Minimal microhematuria (3-10 RBC/HPF)
• Consider renal ultrasound and urinalysis follow-up 1

Intermediate-Risk Patients:

• Age 40-60 years with low-grade microhematuria
• Limited risk factors
• Recommend cystoscopy and upper tract imaging (CTU or ultrasound) 1

High-Risk Patients:

• Age >60 years
• Multiple risk factors
• Gross hematuria (even if resolved)
• Persistent microhematuria
• Require complete evaluation with cystoscopy and CT urography 1

Follow-Up After Negative Evaluation

• For patients with a negative initial evaluation and persistent microhematuria:
  • Annual urinalysis for 2 years 1
  • If microhematuria persists after 2 years with negative evaluations, consider nephrology consultation 1
  • Patients with isolated hematuria should be monitored for development of hypertension, renal insufficiency, or proteinuria 1

Common Pitfalls to Avoid

1. Ignoring microhematuria in anticoagulated patients - anticoagulant therapy does not alter the need for urologic evaluation 1

2. Relying solely on dipstick testing - dipstick positivity should be confirmed with microscopic examination due to limited specificity (65-99%) 1

3. Missing glomerular causes - dysmorphic RBCs or RBC casts require nephrology evaluation even when urologic evaluation is planned 1

4. Inadequate follow-up - even after a negative evaluation, patients with persistent microhematuria require monitoring due to potential for delayed presentation of significant disease 1

5. Over-reliance on urinary cytology - has limited sensitivity in detecting bladder cancer in patients with microhematuria 2