Diagnostic Testing for Hematuria
Confirm True Hematuria First
Before ordering any imaging or invasive tests, confirm microscopic hematuria with ≥3 red blood cells per high-power field on at least two of three properly collected clean-catch midstream urine specimens 1, 2. Dipstick tests alone have only 65-99% specificity and produce false positives from myoglobinuria, hemoglobinuria, or menstrual contamination 1, 3.
Exclude Benign Transient Causes
After confirmation, rule out these reversible causes before proceeding with extensive workup 2:
- Urinary tract infection: Obtain urine culture before antibiotics, treat if positive, then repeat urinalysis 6 weeks post-treatment 3
- Recent vigorous exercise 1
- Menstruation 1
- Recent sexual activity or trauma 2
- Viral illness 2
Critical caveat: Anticoagulation or antiplatelet therapy does NOT explain hematuria and should never defer evaluation—these medications may unmask underlying pathology but do not cause hematuria themselves 1, 3.
Essential Laboratory Tests for All Patients
Core Laboratory Panel
Complete urinalysis with microscopic sediment examination to assess 2:
Serum creatinine, BUN, and complete metabolic panel to evaluate renal function 1, 2
Urine protein-to-creatinine ratio if proteinuria detected (normal <0.2 g/g) 1
Risk-Stratified Additional Testing
Urine cytology is indicated for high-risk patients 2:
- Age >40 years
- Smoking history (especially >30 pack-years)
- Occupational chemical/dye exposure
- History of pelvic irradiation
- Irritative voiding symptoms
- History of gross hematuria
- Analgesic abuse
Imaging Studies: Risk-Based Approach
For Gross (Visible) Hematuria
All patients with gross hematuria require urgent complete urologic evaluation regardless of age 3:
- Multiphasic CT urography (with and without contrast) is the preferred imaging modality with 92% sensitivity and 93% specificity for detecting urologic pathology 3, 4
- This single test evaluates for renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1
Rationale: Gross hematuria carries a 30-40% risk of underlying malignancy, dramatically higher than microscopic hematuria's 2.6-4% risk 3.
For Microscopic Hematuria
Imaging depends on risk stratification 1:
High-risk patients (men ≥60 years, women ≥60 years, >30 pack-year smoking history, occupational exposures, history of gross hematuria):
Intermediate-risk patients (men 40-59 years, women with 10-30 pack-year smoking history):
- Multiphasic CT urography 1
Low-risk patients (age <40 years, never smoker or <10 pack-years, 3-10 RBC/HPF):
- May not require extensive imaging if benign cause identified 1
- Consider renal ultrasound if imaging deemed necessary 1
Important exception: Renal ultrasound alone is insufficient for comprehensive upper tract evaluation in adults 1.
Cystoscopy Requirements
Mandatory cystoscopy for 2, 3:
- All patients with gross hematuria regardless of age
- All patients ≥40 years with microscopic hematuria
- Patients <40 years with risk factors: smoking, occupational exposures, irritative voiding symptoms, or history of gross hematuria
Use flexible cystoscopy as it causes less pain with equivalent or superior diagnostic accuracy compared to rigid cystoscopy 1.
When to Add Nephrology Evaluation
Obtain additional glomerular workup and nephrology referral if 1, 2, 3:
- Proteinuria >500 mg/24 hours (or protein-to-creatinine ratio >0.2)
- Dysmorphic RBCs >80% in urinary sediment
- Red blood cell casts present
- Elevated or rising serum creatinine
- Hypertension developing with persistent hematuria
Additional Nephrology-Directed Tests
When glomerular disease suspected 1:
- Complement levels (C3, C4) for post-infectious glomerulonephritis or lupus nephritis
- Antinuclear antibody (ANA) if lupus suspected
- ANCA testing if vasculitis suspected
- Urine calcium-to-creatinine ratio for hypercalciuria
Critical point: Glomerular disease does not exclude concurrent urologic malignancy—both evaluations must proceed simultaneously 3.
Follow-Up Protocol for Negative Initial Workup
If complete urologic evaluation is negative but hematuria persists 1, 2:
- Repeat urinalysis at 6,12,24, and 36 months
- Monitor blood pressure at each visit
- Repeat voided urine cytology in high-risk patients
- Immediate re-evaluation if:
- Gross hematuria develops
- Significant increase in degree of microscopic hematuria
- New urologic symptoms appear
- Development of hypertension, proteinuria, or glomerular bleeding signs
Special Population Considerations
Pediatric Patients
- Children with isolated microscopic hematuria without proteinuria or dysmorphic RBCs do not require imaging 1
- Renal ultrasound is the preferred modality if imaging needed to assess kidney anatomy before potential biopsy 1
- For gross hematuria in children: urine culture, urine calcium-to-creatinine ratio, and renal/bladder sonography 5
Elderly Males
Even if benign prostatic hyperplasia is present, gross hematuria must be proven to be of prostatic etiology through complete evaluation—BPH does not exclude concurrent malignancy 1.
Women
Women are significantly underreferred for hematuria evaluation (8-28% referral rate vs. 36-47% in men) despite similar cancer risk 3. Apply the same evaluation standards regardless of gender.
Trauma Patients
- Gross hematuria after trauma requires contrast-enhanced CT 1
- Blood at urethral meatus with pelvic fractures requires retrograde urethrography before catheter placement 1
- Isolated microscopic hematuria without clinical findings of visceral trauma does not need emergency investigation 1
Common Pitfalls to Avoid
- Never attribute hematuria solely to anticoagulation without complete workup 1, 3
- Never defer evaluation because bleeding is self-limited 3
- Never rely on dipstick alone—always confirm with microscopy 1, 3
- Never assume BPH explains gross hematuria without proving prostatic source 1
- Never use renal ultrasound alone for comprehensive upper tract evaluation in adults 1
- Never skip cystoscopy in patients ≥40 years or high-risk younger patients 2