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

Evaluation and Management of Hematuria

Initial Confirmation and Assessment

All patients with dipstick-positive hematuria must have microscopic confirmation showing ≥3 red blood cells per high-power field before initiating any further workup. 1, 2

• Dipstick testing alone has limited specificity (65-99%) and should never be relied upon without microscopic examination 3, 4
• For high-risk patients, a single urinalysis with ≥3 RBC/HPF may warrant full evaluation, while lower-risk patients should have 2 of 3 properly collected specimens showing hematuria 3, 4
• Exclude benign causes first: urinary tract infection (obtain urine culture before antibiotics), menstruation, vigorous exercise, sexual activity, viral illness, and trauma 2, 4
• If UTI is confirmed, treat appropriately and repeat urinalysis 6 weeks after treatment to confirm resolution 2
• For suspected benign causes, repeat urinalysis 48 hours after cessation of the potential cause 2

Distinguish Glomerular vs. Non-Glomerular Source

Examine urinary sediment and assess for markers of glomerular disease:

• Glomerular indicators: Dysmorphic RBCs (>80%), red cell casts, significant proteinuria (>500 mg/24 hours), elevated serum creatinine 2, 3
• Non-glomerular indicators: Normal-appearing RBCs without casts, absence of significant proteinuria 3
• If glomerular source is suspected, refer to nephrology for evaluation of renal parenchymal disease 2, 4

Risk Stratification for Urologic Malignancy

All patients with gross hematuria require immediate urologic referral regardless of other factors, as the risk of underlying malignancy exceeds 10%. 1, 2, 5

High-risk factors for urologic malignancy in microscopic hematuria include:

• Age ≥60 years (or >40 years in some guidelines) 1, 3
• Male sex 3
• Smoking history (severity depends on pack-years) 2, 3
• Occupational exposure to chemicals or dyes (benzenes, aromatic amines) 2, 4
• History of gross hematuria 4
• Irritative voiding symptoms 2
• History of pelvic irradiation 2, 4
• Analgesic abuse 2, 4
• Chronic indwelling foreign body 4

Urologic Evaluation for Non-Glomerular Hematuria

For patients with confirmed non-glomerular microscopic hematuria without a benign cause, refer to urology for cystoscopy and upper tract imaging. 1, 2

High-Risk Patients (Age ≥60 years, smoking history, male sex, or other risk factors):

• CT urography is the preferred imaging modality to identify hydronephrosis, urinary calculi, and renal/ureteral lesions 1, 3
• Cystoscopy (flexible preferred over rigid for patient comfort and equivalent diagnostic accuracy) to evaluate for bladder masses, urethral stricture disease, and benign prostatic hyperplasia 1, 3
• Urine cytology may be considered if risk factors for carcinoma in situ or irritative voiding symptoms are present 3

Lower-Risk Patients (Age <40 years without risk factors):

• Initial cystoscopy may be deferred, but urinary cytology should be performed 1
• However, the American College of Physicians recommends considering urology referral for cystoscopy and imaging even in lower-risk patients with confirmed microscopic hematuria 1, 2

Critical caveat: Antiplatelet or anticoagulant therapy does not alter the need for urologic evaluation—pursue full workup regardless 1, 2, 4

Follow-Up for Negative Initial Evaluation

If initial urologic evaluation is negative but hematuria persists:

• Repeat urinalysis, voided urine cytology, and blood pressure determination at 6,12,24, and 36 months 1, 2, 4
• Cytology detects most high-grade tumors and carcinomas in situ, particularly with repeated testing 1
• Immediate urologic re-evaluation is required if: (1) gross hematuria develops, (2) abnormal urinary cytology, (3) irritative voiding symptoms without infection, or (4) significant increase in degree of microscopic hematuria 1, 3
• If none of these occur within 3 years, further urologic monitoring is not required 1
• Consider nephrology referral if hematuria persists with development of hypertension, proteinuria, or evidence of glomerular bleeding 1, 2

Key Pitfalls to Avoid

• Never screen asymptomatic adults with urinalysis for cancer detection 1
• Never obtain urinary cytology or urine-based molecular markers in the initial evaluation of hematuria (except in specific high-risk scenarios noted above) 1
• Do not attribute hematuria solely to anticoagulation without complete evaluation 1, 2
• Do not delay evaluation in high-risk patients, as early detection of urologic malignancy significantly impacts mortality and morbidity 3
• Always include questions about gross hematuria in routine review of systems, as it is often underreported but significantly increases cancer risk (odds ratio 7.2) 2