What is the recommended diagnostic workup and management for an adult patient presenting with hematuria?

Evaluation and Management of Hematuria in Adults

Initial Confirmation and Definition

Confirm true hematuria with microscopic urinalysis showing ≥3 red blood cells per high-power field (RBC/HPF) on at least two of three properly collected clean-catch midstream urine specimens before initiating any workup. 1, 2

• Dipstick testing alone has limited specificity (65-99%) and produces false positives from myoglobin, hemoglobin, menstruation, or contaminants 1, 2
• For high-risk patients (age ≥60 years, smoking history, occupational exposures), a single urinalysis with ≥3 RBC/HPF may warrant full evaluation 1
• Microscopic hematuria is defined as ≥3 RBC/HPF; 0-2 RBC/HPF falls within normal range and does not require urologic workup 3

Exclude Benign Transient Causes

Before proceeding with extensive evaluation, rule out:

• Urinary tract infection: Obtain urine culture before antibiotics; if positive, treat appropriately and repeat urinalysis 6 weeks after treatment completion 1, 2
• Recent vigorous exercise, sexual activity, viral illness, trauma, or menstruation: Repeat urinalysis 48 hours after cessation 1, 2
• If hematuria resolves after treating infection or eliminating transient causes, no further evaluation is needed in low-risk patients 2

Distinguish Glomerular from Urologic Sources

Examine urinary sediment for dysmorphic RBCs and red cell casts to differentiate glomerular from non-glomerular bleeding:

Glomerular Indicators (Nephrology Referral)

• >80% dysmorphic red blood cells on phase-contrast microscopy 1, 3
• Red cell casts (pathognomonic for glomerular disease) 1, 2
• Significant proteinuria: spot urine protein-to-creatinine ratio >0.5 g/g (or >500 mg/24 hours) 1, 2
• Elevated serum creatinine or declining renal function 1, 2
• Tea-colored or cola-colored urine suggests glomerular source 3

Non-Glomerular Indicators (Urologic Evaluation)

• Normal-appearing RBCs (>80%) without casts 1
• Minimal or no proteinuria 3
• Normal renal function 1

Important caveat: The presence of glomerular features does NOT eliminate the need for urologic evaluation—malignancy can coexist with medical renal disease, so complete both evaluations 3 1

Risk Stratification for Urologic Malignancy

High-Risk Features (Require Cystoscopy + CT Urography)

• Age ≥60 years (both men and women) 1
• Smoking history >30 pack-years 1, 2
• Any history of gross hematuria 1, 2
• Occupational exposure to chemicals/dyes (benzenes, aromatic amines) 1, 2
• >25 RBC/HPF on single urinalysis 2
• Irritative voiding symptoms (urgency, frequency, nocturia) without documented infection 1, 2

Intermediate-Risk Features (Shared Decision-Making)

• Men age 40-59 years or women age 50-59 years 2
• Smoking history 10-30 pack-years 2
• 11-25 RBC/HPF on single urinalysis 2

Low-Risk Features (May Defer Extensive Imaging)

• Women <50 years or men <40 years 2
• Never smoker or <10 pack-years 2
• 3-10 RBC/HPF 2

Complete Urologic Evaluation for High-Risk Patients

Upper Tract Imaging

Multiphasic CT urography is the preferred imaging modality for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1, 2, 4

• Includes unenhanced, nephrographic, and excretory phases to comprehensively evaluate kidneys, collecting systems, ureters, and bladder 1
• If CT is contraindicated (renal insufficiency, contrast allergy), use MR urography or renal ultrasound with retrograde pyelography 1
• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation 1

Lower Tract Evaluation

Cystoscopy is mandatory for:

• All patients with gross hematuria 1, 2
• All patients ≥40 years with microscopic hematuria 1, 2
• Microscopic hematuria patients with any high-risk features 1, 2

Flexible cystoscopy is preferred over rigid cystoscopy because it causes less pain, has fewer post-procedure symptoms, and demonstrates equivalent or superior diagnostic accuracy 1, 3

Adjunctive Testing

• Voided urine cytology may be considered in high-risk patients (age >60, smoking >30 pack-years, occupational exposures, irritative voiding symptoms) to detect high-grade urothelial carcinomas and carcinoma in situ 1, 2
• Do NOT use urine cytology or molecular markers as the initial evaluation tool 3

Laboratory Testing

• Serum creatinine to assess renal function 1, 2
• Complete urinalysis with microscopy 1, 2
• Urine culture if infection suspected 1, 2

Gross (Visible) Hematuria

All adults with gross hematuria require urgent urologic referral with cystoscopy and upper tract imaging, even if bleeding is self-limited. 1, 2, 3

• Gross hematuria carries a 30-40% risk of malignancy 1, 2, 3
• Patients reporting prior gross hematuria have significantly increased cancer risk even if currently only microscopic 3
• Never ignore gross hematuria—delays in diagnosis beyond 9 months are associated with worse cancer-specific survival 3

Critical Pitfalls to Avoid

• Do NOT attribute hematuria to anticoagulation or antiplatelet therapy as the sole explanation—these medications may unmask underlying pathology but do not cause hematuria; evaluation must proceed regardless 1, 2, 3
• Do NOT defer evaluation in patients taking anticoagulants or antiplatelet agents 1, 2, 3
• Do NOT rely solely on dipstick testing without microscopic confirmation 1, 2
• Do NOT delay evaluation while awaiting "contrast washout" after recent CT—contrast does not cause hematuria 3
• Do NOT assume hematuria is benign based on age alone if significant hematuria (>30 RBC/HPF) is present 3

Follow-Up Protocol for Negative Initial Evaluation

If the complete workup is negative but hematuria persists:

• Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit 1, 2
• After two consecutive negative annual urinalyses, no further testing is necessary 3
• Consider repeat complete evaluation within 3-5 years for persistent hematuria in high-risk patients 1, 2

Immediate re-evaluation is warranted if:

• Gross hematuria develops 1, 2
• Significant increase in degree of microscopic hematuria occurs 1, 2
• New urologic symptoms appear 1, 2
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 1, 2

Nephrology Referral Indications

Refer to nephrology when any of the following are present:

• Dysmorphic RBCs >80% or red cell casts 1, 2
• Significant proteinuria: protein-to-creatinine ratio >0.5 g/g (or >500-1000 mg/24 hours) 1, 2
• Elevated serum creatinine or declining renal function 1, 2
• Hypertension accompanying hematuria and proteinuria 1, 2
• Persistent hematuria that develops any of the above features during follow-up 1, 2

Complete both nephrologic AND urologic evaluations when glomerular features are present—do not assume one excludes the other 1, 3

Special Populations

Pediatric Considerations

• Children with isolated microscopic hematuria without proteinuria or dysmorphic RBCs do not require imaging—clinical follow-up is appropriate 3
• Renal ultrasound is the preferred modality in children to assess anatomy before potential renal biopsy 3
• Gross hematuria in children requires renal and bladder ultrasound to exclude nephrolithiasis, anatomic abnormalities, and rarely tumors 3

Patients with UTI and Persistent Hematuria

• If microscopic hematuria persists 6 weeks after completing antibiotics, proceed with full urologic evaluation regardless of infection treatment 1, 2
• Do NOT prescribe additional courses of antibiotics—this delays cancer diagnosis and provides false reassurance 3