What is the appropriate evaluation and treatment for hematuria (blood in urine)?

Evaluation and Management of Hematuria

Immediate Confirmation and Classification

All hematuria requires microscopic confirmation showing ≥3 red blood cells per high-power field before initiating any workup—dipstick positivity alone is insufficient due to only 65-99% specificity. 1, 2

• Obtain microscopic urinalysis on at least two of three properly collected clean-catch midstream specimens to confirm true hematuria 1, 3
• Gross (visible) hematuria mandates immediate urologic referral regardless of whether it resolves spontaneously, as it carries a 30-40% malignancy risk 1, 2
• Microscopic hematuria (≥3 RBC/HPF) requires risk stratification before determining evaluation intensity 2, 4

Exclude Benign Transient Causes First

Before proceeding with extensive evaluation, systematically exclude:

• Menstruation in women—repeat urinalysis 48 hours after menses ends 2, 4
• Vigorous exercise—repeat urinalysis 48 hours after cessation 2, 4
• Sexual activity and minor trauma 4
• Urinary tract infection—obtain urine culture, treat if positive, and repeat urinalysis 6 weeks after completing antibiotics to confirm resolution 4, 2
• Recent viral illness 4

Critical pitfall: Never attribute hematuria solely to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria themselves. 1, 2

Risk Stratification for Malignancy

Use the following algorithm to determine evaluation intensity:

High-Risk Features (Require Full Urologic Evaluation)

• Age ≥60 years in either sex 2, 4
• Smoking history >30 pack-years 2, 4

• 25 RBC/HPF on microscopic examination 4

• Any history of gross hematuria 2, 4
• Occupational exposure to chemicals/dyes (benzenes, aromatic amines) 1, 4
• Irritative voiding symptoms without infection 2, 4
• History of pelvic irradiation 4

Intermediate-Risk Features

• Women age 50-59 years or men age 40-59 years 4
• Smoking history 10-30 pack-years 4
• 11-25 RBC/HPF on microscopic examination 4

Low-Risk Features

• Women age <50 years or men age <40 years 4
• Never smoker or <10 pack-years 4
• 3-10 RBC/HPF on single urinalysis 4
• No additional risk factors 4

Distinguish Glomerular from Non-Glomerular Sources

Examine urinary sediment for dysmorphic RBCs and red cell casts—this determines whether nephrology or urology leads the evaluation. 2, 3

Glomerular Source Indicators (Nephrology Referral)

• 80% dysmorphic red blood cells on microscopy 2, 3

• Red cell casts (pathognomonic for glomerular disease) 2, 3
• Tea-colored urine 2
• Significant proteinuria (protein-to-creatinine ratio >0.2 g/g or >500 mg/24 hours) 2, 3
• Elevated serum creatinine or declining renal function 2, 3
• Associated hypertension 2, 3

Non-Glomerular Source Indicators (Urologic Evaluation)

• 80% normal-appearing red blood cells 2

• Absence of proteinuria or minimal proteinuria 2
• Normal renal function 2

Complete Urologic Evaluation for Non-Glomerular Hematuria

For High-Risk and Intermediate-Risk Patients

Mandatory components include both upper tract imaging and cystoscopy—neither alone is sufficient. 2, 3

Upper Tract Imaging

• Multiphasic CT urography is the preferred modality for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis 2, 3
• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation 2
• Consider radiation exposure risks in younger patients when weighing CT benefits 1

Lower Tract Evaluation

• Cystoscopy is mandatory for all patients ≥40 years old and younger patients with risk factors 2, 3
• Flexible cystoscopy causes less pain with equivalent or superior diagnostic accuracy compared to rigid cystoscopy 2
• Bladder transitional cell carcinoma is the most frequently diagnosed malignancy in hematuria cases 2

Laboratory Testing

• Serum creatinine to assess renal function 2, 3
• Complete urinalysis with microscopy 2
• Voided urine cytology for high-risk patients (age >40, smoking history, occupational exposures, irritative symptoms, history of gross hematuria) 3, 4
• Do NOT obtain urinary cytology or urine-based molecular markers in the initial evaluation of low-risk microscopic hematuria 1

For Low-Risk Patients

Low-risk patients may undergo repeat urinalysis in 6 months or proceed with evaluation based on shared decision-making. 4

Follow-Up Protocol After Negative Initial Evaluation

If comprehensive evaluation reveals no abnormality but hematuria persists:

• Repeat urinalysis at 6,12,24, and 36 months 2, 3, 4
• Monitor blood pressure at each visit 2, 3, 4
• Consider repeat cystoscopy and imaging within 3-5 years for persistent or recurrent hematuria, particularly in high-risk populations 4

Triggers for Immediate Re-Evaluation

• Development of gross hematuria 2, 4
• Significant increase in degree of microscopic hematuria 2, 4
• New urologic symptoms (flank pain, dysuria, irritative voiding) 2, 4
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 2, 3, 4

Nephrology Referral Criteria

Refer to nephrology when glomerular disease is suspected or confirmed: 2, 3

• Proteinuria >500 mg/24 hours or protein-to-creatinine ratio >0.2 g/g 2, 3

• 80% dysmorphic RBCs or presence of red cell casts 2, 3

• Elevated serum creatinine or declining renal function 2, 3
• Hematuria with hypertension 2, 3
• Persistent hematuria with development of any glomerular indicators 2, 3

Special Populations and Considerations

Elderly Males with Benign Prostatic Hyperplasia

BPH can cause hematuria but does not exclude concurrent malignancy—gross hematuria from BPH must be proven through appropriate evaluation, not assumed. 2

Patients on Anticoagulation

Evaluate identically to non-anticoagulated patients, as malignancy risk is similar regardless of anticoagulation status. 1, 2, 4

Children

• Isolated microscopic hematuria without proteinuria or dysmorphic RBCs does not require imaging 2
• Ultrasound is the preferred modality for children to assess kidney anatomy before potential renal biopsy 2
• Glomerulonephritis and congenital anomalies are common causes in pediatric populations 2

Post-Traumatic Hematuria

• Gross hematuria after trauma requires contrast-enhanced CT 2
• Blood at urethral meatus with pelvic fractures requires retrograde urethrography before catheter placement 2
• Isolated microscopic hematuria without clinical findings of visceral trauma does not need emergency investigation 2

Common Pitfalls to Avoid

• Never screen asymptomatic adults with urinalysis for cancer detection 1
• Never defer evaluation because patient is on anticoagulation or antiplatelet therapy 1, 2
• Never ignore gross hematuria even if self-limited—30-40% harbor malignancy 1, 2
• Never rely on dipstick alone—always confirm with microscopic examination 1, 2
• Never assume medications like tadalafil (Cialis) cause hematuria—they do not 2
• Never obtain urinary cytology or molecular markers in initial low-risk microscopic hematuria evaluation 1