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

Evaluation and Management of Hematuria

Immediate Action Based on Presentation

All patients with gross hematuria require immediate urologic referral for cystoscopy and imaging, regardless of whether the bleeding is self-limited or the patient is on anticoagulation. 1, 2

For microscopic hematuria, confirm true hematuria with microscopic examination showing ≥3 red blood cells per high-power field before initiating any evaluation—dipstick results alone are insufficient due to limited specificity (65-99%). 1, 2, 3

Initial Evaluation Algorithm

Step 1: Confirm and Exclude Benign Causes

• Repeat urinalysis 48 hours after cessation of potential transient causes: menstruation, vigorous exercise, sexual activity, trauma, viral illness, or recent urinary tract infection 2, 4
• If UTI is suspected, obtain urine culture; if positive, treat and repeat urinalysis 6 weeks post-treatment to confirm resolution 4
• Do not attribute hematuria solely to antiplatelet or anticoagulant therapy—pursue full evaluation regardless 1, 4

Step 2: Determine Source (Glomerular vs. Non-Glomerular)

Examine urinary sediment for:

• Dysmorphic RBCs >80% = glomerular source 2, 4
• Red cell casts = glomerular source 2, 4
• Normal-appearing RBCs without casts = urologic (non-glomerular) source 3

Measure:

• Serum creatinine to assess renal function 2, 4
• 24-hour urine protein if dipstick shows proteinuria 4

Risk Stratification for Urologic Malignancy

High-Risk Criteria (Require Complete Urologic Evaluation)

• Age ≥40 years (some guidelines use ≥60 years for highest risk) 2, 4, 3
• Smoking history (risk increases with pack-years) 2, 4, 3
• Male sex 3
• Occupational exposure to chemicals/dyes (benzenes, aromatic amines) 2, 4
• History of gross hematuria 2, 4
• Irritative voiding symptoms 2, 4
• History of pelvic irradiation 2, 4
• Analgesic abuse 2, 4

Complete Urologic Evaluation (For High-Risk or Non-Glomerular Hematuria)

Imaging

CT urography (multiphasic) is the preferred imaging modality for comprehensive upper urinary tract evaluation—it identifies hydronephrosis, urinary calculi, and renal/ureteral lesions. 2, 3 The 2016 American College of Physicians guideline notes important concerns about radiation exposure in younger, lower-risk patients, where CT may carry greater carcinogenesis risk than cancer detection benefit. 1

Cystoscopy

Mandatory for all patients ≥40 years of age and those <40 years with risk factors (smoking, occupational exposures, irritative voiding symptoms, history of gross hematuria). 2, 3 Cystoscopy evaluates for bladder masses, urethral stricture disease, and benign prostatic hyperplasia. 3

Urine Cytology

• Do not obtain urinary cytology or urine-based molecular markers in the initial evaluation of hematuria 1
• Consider urine cytology only in patients with risk factors for transitional cell carcinoma or carcinoma in situ, particularly with irritative voiding symptoms 2, 3

Nephrology Referral Criteria (For Glomerular Source)

Refer to nephrology if any of the following are present:

• Proteinuria >500 mg/24 hours 2, 4
• Red cell casts or dysmorphic RBCs >80% 2, 4
• Elevated serum creatinine 2, 4
• Development of hypertension with persistent hematuria 2, 4

Follow-Up for Negative Initial Evaluation

If urologic evaluation is negative but microscopic hematuria persists:

• Repeat urinalysis at 6,12,24, and 36 months 2, 4
• Monitor blood pressure at each visit 2, 4
• Persistent isolated microscopic hematuria carries long-term risk for chronic kidney disease (particularly IgA nephropathy, Alport syndrome, thin basement membrane disease)—the term "benign hematuria" is a misnomer that should be abandoned 5
• Repeat urologic evaluation if patient develops gross hematuria, significant increase in degree of microscopic hematuria, or new urologic symptoms 3

Critical Pitfalls to Avoid

• Never screen asymptomatic adults with urinalysis for cancer detection—this is low-value care 1
• Never delay evaluation in high-risk patients—early detection of urologic malignancy significantly impacts mortality and morbidity 3
• Never rely on dipstick alone—always confirm with microscopic examination 1, 2, 3
• Research shows that 64-77% of primary care physicians underutilize urologic referral for microscopic hematuria, and even gross hematuria referral rates are only 69-77%, leading to delayed cancer diagnosis 6, 7
• Always ask about history of gross hematuria in routine review of systems—visible blood in urine increases cancer risk (odds ratio 7.2) but is often underreported 4