What is the evaluation and management approach for an adult patient with asymptomatic hematuria (blood in the urine)?

Evaluation and Management of Asymptomatic Hematuria

Adults with asymptomatic hematuria require risk-stratified evaluation to exclude urologic malignancy and renal parenchymal disease, with the evaluation pathway determined by patient age, smoking history, degree of hematuria, and presence of glomerular disease indicators.

Initial Confirmation and Exclusion of Benign Causes

• Confirm true microscopic hematuria with microscopic urinalysis showing ≥3 red blood cells per high-power field on at least two of three properly collected clean-catch midstream specimens before initiating any workup 1, 2.
• Dipstick testing alone is insufficient due to limited specificity (65-99%) and can produce false positives from myoglobinuria, hemoglobinuria, or menstrual contamination 3, 2.
• Exclude transient benign causes including menstruation, vigorous exercise within 48 hours, recent sexual activity, viral illness, trauma, and urinary tract infection before proceeding 3, 1, 2.
• If urinary tract infection is suspected, obtain urine culture before starting antibiotics, treat appropriately, then repeat urinalysis 6 weeks after treatment completion to confirm resolution 4, 2.
• Repeat urinalysis 48 hours after cessation of the suspected benign cause (such as exercise or menstruation) to confirm resolution 4.

Risk Stratification for Urologic Malignancy

High-risk patients (requiring full urologic evaluation with cystoscopy and upper tract imaging) include 3, 1, 2:

• Age ≥60 years (men) or ≥60 years (women)
• Smoking history >30 pack-years

• 25 RBCs per high-power field on single urinalysis

• History of gross hematuria (even if currently microscopic)
• Occupational exposure to chemicals or dyes (benzenes, aromatic amines)
• History of urologic disorders or pelvic irradiation
• Irritative voiding symptoms without infection
• Analgesic abuse
• Recurrent urinary tract infections despite appropriate treatment

Intermediate-risk patients (shared decision-making regarding cystoscopy and imaging) include 1, 2:

• Women age 50-59 years or men age 40-59 years
• Smoking history 10-30 pack-years
• 11-25 RBCs per high-power field on single urinalysis

Low-risk patients (may defer some components of evaluation) include 1, 2:

• Women age <50 years or men age <40 years
• Never smoker or <10 pack-years smoking history
• 3-10 RBCs per high-power field on single urinalysis
• No additional risk factors

Distinguishing Glomerular from Non-Glomerular Sources

Before proceeding with urologic evaluation, assess for indicators of primary renal/glomerular disease 3, 2:

Glomerular indicators requiring nephrology referral:

• Dysmorphic red blood cells >80% on urinary sediment examination with phase contrast microscopy 3, 2
• Red blood cell casts (virtually pathognomonic for glomerular bleeding) 3
• Significant proteinuria >500 mg per 24 hours (persistent or increasing) or >1,000 mg per 24 hours 3, 2
• Elevated serum creatinine based on age and sex-specific normal ranges 3
• Tea-colored or cola-colored urine (suggests glomerular source) 1

If any glomerular indicators are present, refer to nephrology for evaluation of renal parenchymal disease while also completing urologic evaluation if hematuria persists 3, 4, 2.

Complete Urologic Evaluation for Non-Glomerular Hematuria

For high-risk patients and those with gross hematuria, perform the following mandatory evaluations 1, 2:

Upper Tract Imaging

• Multiphasic CT urography is the preferred imaging modality for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis, including unenhanced, nephrographic phase, and excretory phase images 1, 2.
• If CT is contraindicated (renal insufficiency, contrast allergy), use MR urography or renal ultrasound with retrograde pyelography as alternatives, though less optimal 1.
• Traditional intravenous urography remains acceptable but has limited sensitivity for small renal masses 1.

Lower Tract Evaluation

• Cystoscopy is mandatory for all patients age ≥40 years with microscopic hematuria and all patients with gross hematuria to detect bladder tumors and carcinoma in situ 1, 2.
• Flexible cystoscopy is preferred over rigid cystoscopy as it causes less pain, has fewer post-procedure symptoms, and demonstrates equivalent or superior diagnostic accuracy 1.

Laboratory Testing

• Serum creatinine to assess renal function 3, 1
• Complete urinalysis with microscopy 1
• Urine culture if infection suspected 1
• Voided urine cytology in high-risk patients only (age >60 years, smoking history, occupational exposure) to detect high-grade urothelial cancers 1

Follow-Up After Negative Initial Evaluation

If initial workup is negative but hematuria persists 1, 4, 2:

• Repeat urinalysis at 6,12,24, and 36 months
• Monitor blood pressure at each visit
• Consider comprehensive re-evaluation with repeat cystoscopy and imaging in 3-5 years if hematuria persists or recurs, particularly in high-risk populations

Immediate re-evaluation is warranted if 1, 2:

• Gross hematuria develops (30-40% malignancy risk)
• Significant increase in degree of microscopic hematuria occurs
• New urologic symptoms appear (flank pain, dysuria, irritative voiding symptoms)
• Development of hypertension, proteinuria, or evidence of glomerular bleeding

Critical Pitfalls to Avoid

• Never attribute hematuria solely to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria themselves, and evaluation should proceed regardless 1, 2.
• Gross hematuria requires urgent urologic referral even if self-limited, as it carries a 30-40% risk of malignancy 1, 4.
• Do not delay evaluation in patients with rapid recurrence of urinary tract infection with the same organism, as this may indicate calculus disease 4.
• Do not stop at symptom resolution alone—documented microscopic confirmation of resolution of hematuria is required after treating presumed benign causes 4.
• Maintain equal vigilance across sexes, as women are significantly underreferred for hematuria evaluation despite similar cancer risk 2.
• Patients with isolated glomerular hematuria (dysmorphic RBCs, red cell casts) require nephrology follow-up at six-month intervals even if initial evaluation is negative 5.