How do you evaluate a patient with microscopic hematuria (4 RBC/hpf) on urinalysis?

Evaluation of Microscopic Hematuria (4 RBC/hpf)

Patients with microscopic hematuria (≥3 RBC/HPF) should undergo a complete evaluation including history, physical examination, and appropriate diagnostic testing to rule out urologic malignancy and other significant conditions, regardless of anticoagulant use. 1

Definition and Confirmation

• Microscopic hematuria is defined as >3 red blood cells per high-power field (RBC/HPF) on microscopic evaluation of a single, properly collected urine specimen 1
• A positive urine dipstick test should always be confirmed with microscopic examination due to limited specificity (65-99%) 1
• Dipstick testing alone is insufficient as it measures peroxidase activity, which can be confounded by factors including povidone iodine use, myoglobinuria, and dehydration 1

Initial Evaluation

• Perform a comprehensive history and physical examination to assess risk factors for genitourinary malignancy, medical renal disease, and gynecologic/non-malignant genitourinary causes 1
• Risk factors for significant urologic disease include:
  • Age >40 years 1, 2
  • Smoking history 1, 2
  • Occupational exposure to chemicals or dyes (benzenes or aromatic amines) 1, 3
  • History of gross hematuria 1, 2
  • Irritative voiding symptoms 3
  • History of urinary tract infection 3
  • Analgesic abuse 3
  • History of pelvic irradiation 3
• Physical examination should include blood pressure measurement and genitourinary examination as clinically indicated 1
• Patients on anticoagulants should receive the same evaluation as those not on anticoagulants, as they have similar malignancy risk 1, 4

Diagnostic Approach

For all patients:

• Examine urinary sediment for dysmorphic red blood cells and red cell casts (suggesting glomerular origin) 3, 2
• Assess for proteinuria and measure serum creatinine 3, 2
• Glomerular source indicators include significant proteinuria (>500 mg/24 hours), dysmorphic RBCs (>80%), red cell casts, and elevated serum creatinine 3

For patients with non-glomerular hematuria:

• Rule out benign causes including exercise, viral illness, and urinary tract infection 3
• If urinary tract infection is suspected, obtain urine culture; if positive, treat appropriately and repeat urinalysis 6 weeks after treatment 3
• For suspected benign causes, repeat urinalysis 48 hours after cessation of the potential cause 3

Risk-stratified approach:

• High-risk patients (age ≥60 years, smoking history, >25 RBC/HPF, history of gross hematuria):
  • Complete urologic evaluation including cystoscopy and upper tract imaging (CT urography preferred) 2, 4
  • Consider urine cytology if there are risk factors for carcinoma in situ or irritative voiding symptoms 2
• Intermediate-risk patients:
  • Cystoscopy and urinary tract ultrasound 5
• Low-risk patients:
  • Consider repeat urinalysis in 6 months or cystoscopy with urinary tract ultrasound through shared decision-making 5

Follow-up Recommendations

• For patients with gynecologic or non-malignant genitourinary sources of microscopic hematuria, repeat urinalysis following resolution of the condition 1
• For patients with persistent hematuria after negative initial evaluation, repeat urinalysis at 6,12,24, and 36 months 3, 4
• Consider nephrology referral if hematuria persists with development of hypertension, proteinuria, or evidence of glomerular bleeding 3, 2
• Further workup is warranted if the patient develops gross hematuria, significant increase in degree of microscopic hematuria, or new urologic symptoms after a negative evaluation 2

Important Caveats

• The prevalence of asymptomatic microscopic hematuria varies from 0.19% to as high as 21%, with higher rates in older men 1
• In approximately 3% of patients evaluated for microscopic hematuria, an underlying cancer may be detected 1
• The risk of malignancy increases with the degree of hematuria (number of RBCs per HPF) 2, 6
• Early detection of urologic malignancy significantly impacts mortality and morbidity 2
• The high-power field method for detecting RBCs has limitations in sensitivity compared to direct counting methods 7