What is the recommended workup for asymptomatic hematuria (blood in urine)?

Workup for Asymptomatic Hematuria

All patients with asymptomatic hematuria require confirmation with microscopic examination (≥3 RBCs/high-power field), followed by exclusion of benign causes, and then a complete urologic evaluation including upper tract imaging and cystoscopy to detect potentially life-threatening malignancies. 1

Initial Confirmation and Benign Cause Exclusion

• Confirm true hematuria with microscopic urinalysis showing ≥3 red blood cells per high-power field, rather than relying solely on dipstick results 2
• Exclude benign transient causes including menstruation, vigorous exercise, sexual activity, trauma, viral illness, and medications 1, 2
• Repeat urinalysis 48 hours after cessation of the suspected benign cause; if hematuria resolves, no further evaluation is needed 1, 2
• Obtain clean-catch urine specimen; use catheterization in women if vaginal contamination is suspected or in obese patients where clean-catch is unreliable 1
• Rule out urinary tract infection with urine culture; if positive, treat appropriately and repeat urinalysis 6 weeks after treatment—if hematuria resolves, no additional workup is necessary 1, 2

Laboratory Evaluation

• Comprehensive urinalysis with sediment examination to determine the number of RBCs/HPF, presence of dysmorphic RBCs (>80% suggests glomerular source), red cell casts, white blood cells, bacteria, and degree of proteinuria 1, 3, 4
• Measure serum creatinine to assess renal function 1, 3
• Urine cytology is recommended in all patients with risk factors for transitional cell carcinoma (age >40 years, smoking history, occupational chemical/dye exposure, history of pelvic irradiation, irritative voiding symptoms, history of gross hematuria, analgesic abuse) 1, 2
• In patients age ≥80 years, urine cytology should be performed due to high risk for transitional cell carcinoma 3

Determine Source: Glomerular vs. Non-Glomerular

Glomerular source indicators (prompt nephrology evaluation):

• Significant proteinuria (>500 mg/24 hours) 1, 3, 4
• Red cell casts 1, 3, 4
• Dysmorphic RBCs (>80%) 3, 2, 4
• Elevated serum creatinine or renal insufficiency 1, 3
• Development of hypertension with persistent hematuria 1

Non-glomerular (urologic) source indicators (proceed with complete urologic evaluation):

• Normal-shaped RBCs 3, 2
• Minimal or no proteinuria 3, 2
• Normal serum creatinine 3

Complete Urologic Evaluation (for Non-Glomerular Source)

Upper tract imaging:

• CT urography is the preferred imaging modality for comprehensive evaluation of the upper urinary tract in adults with hematuria 3, 4
• MR urography is an alternative if CT is contraindicated 3
• Renal ultrasound with retrograde pyelography can be considered if CT and MR are not feasible 3

Cystoscopy:

• Cystoscopy is mandatory in all patients ≥40 years of age and in patients <40 years with risk factors for bladder cancer (smoking, occupational exposures, irritative voiding symptoms, history of gross hematuria) 1, 3
• Cystoscopy may be deferred initially in patients <40 years without risk factors, but urine cytology should be performed; if cytology shows malignant or atypical cells, cystoscopy is required 1
• Flexible cystoscopy is preferred as it causes less pain, has fewer post-procedure symptoms, and is at least equivalent in diagnostic accuracy to rigid cystoscopy 1

Follow-Up for Negative Initial Evaluation

For patients with persistent hematuria after negative urologic workup:

• Repeat urinalysis yearly at 6,12,24, and 36 months 1, 3
• Monitor blood pressure at each follow-up visit 1, 3
• Consider repeat urine cytology at follow-up intervals 1, 4
• Repeat complete evaluation (imaging and cystoscopy) within 3-5 years should be considered for persistent or recurrent hematuria, particularly in high-risk patients 1

Immediate urologic re-evaluation is required if:

• Gross hematuria develops 1, 3
• Abnormal urinary cytology is detected 1, 3
• Irritative voiding symptoms develop in the absence of infection 1, 3

Nephrology referral is indicated if:

• Hematuria persists with development of hypertension, proteinuria (>500 mg/24 hours), or evidence of glomerular bleeding (red cell casts, dysmorphic RBCs) 1, 3, 2

Critical Pitfalls to Avoid

• Never attribute hematuria solely to antiplatelet or anticoagulant therapy without completing full evaluation 3, 2
• Do not delay urologic referral while waiting for other test results, especially in patients with gross hematuria or high-risk features 3
• Do not assume resolution of hematuria means no further workup is needed in high-risk patients, as hematuria can precede bladder cancer diagnosis by many years 1
• Patients with enlarged prostate or non-obstructing stones still require full evaluation as malignant causes may be masked by these benign findings 1