What is the appropriate workup for a patient presenting with hematuria (blood in urine)?

Hematuria Workup

All patients with hematuria require confirmation with microscopic urinalysis showing ≥3 RBCs per high-power field on at least two of three properly collected clean-catch midstream specimens before initiating any workup, as dipstick testing alone has limited specificity (65-99%). 1, 2

Initial Confirmation and Documentation

• Verify true hematuria by obtaining microscopic urinalysis on 2-3 separate specimens to confirm ≥3 RBCs/HPF, as dipstick positivity alone is insufficient 1, 2
• Exclude pseudohematuria from menstruation, vigorous exercise within 48 hours, recent sexual activity, or medications/foods that discolor urine 1, 3
• Document whether hematuria is gross (visible) or microscopic (only detected under microscope) 1

Critical Pearl: Gross hematuria carries a 30-40% malignancy risk and requires urgent urologic referral even if self-limited—never ignore it 1, 3, 2

Risk Stratification for Malignancy

Once true hematuria is confirmed, stratify patients using the following high-risk features 1, 2:

High-Risk Features (Require Full Urologic Evaluation)

• Age: Males ≥60 years, females ≥60 years 1, 2
• Smoking: >30 pack-years 1, 2
• Any history of gross hematuria (even if currently microscopic) 1, 2
• Degree of hematuria: >25 RBCs/HPF 3
• Occupational exposure to benzenes, aromatic amines, or other chemicals/dyes 1, 3
• Irritative voiding symptoms (urgency, frequency, nocturia) without documented infection 1, 3

Intermediate-Risk Features

• Males 40-59 years 1
• Smoking 10-30 pack-years 1
• 10-25 RBCs/HPF 3

Low-Risk Features

• Women <60 years, men <40 years 1
• Never smoker or <10 pack-years 1
• 3-10 RBCs/HPF 1

Malignancy rates: High-risk 1.3-6.3%, intermediate-risk 0.2-3.1%, low-risk 0-0.4% 2

Distinguish Glomerular vs. Non-Glomerular Source

This distinction determines whether nephrology, urology, or both specialties should evaluate the patient 1, 2:

Glomerular Indicators (Nephrology Referral)

• Tea-colored or cola-colored urine 1, 3
• >80% dysmorphic RBCs on phase-contrast microscopy 1, 3
• Red blood cell casts (pathognomonic for glomerular disease) 1, 3
• Significant proteinuria: spot protein-to-creatinine ratio >0.5 g/g or >1.0 g/day on 24-hour collection 1, 2
• Elevated serum creatinine or declining renal function 1, 2
• Hypertension accompanying hematuria 1, 2

Non-Glomerular Indicators (Urologic Evaluation)

• Bright red blood suggesting lower urinary tract source 3
• >80% normal (eumorphic) RBCs 1, 3
• Absence of proteinuria or only trace amounts 3
• Normal serum creatinine 2

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 when glomerular features are present 1

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

Upper Tract Imaging

• Multiphasic CT urography is the preferred modality, including unenhanced, nephrographic, and excretory phases to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1, 3, 2
• Alternative imaging if CT contraindicated: MR urography or renal ultrasound with retrograde pyelography (though less optimal) 3
• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation 1

Lower Tract Evaluation

• Flexible cystoscopy is mandatory for all patients with gross hematuria and intermediate-to-high-risk microscopic hematuria to visualize bladder mucosa, urethra, and ureteral orifices 1, 3, 2
• Flexible cystoscopy is preferred over rigid cystoscopy (less pain, fewer post-procedure symptoms, equivalent diagnostic accuracy) 1, 2

Laboratory Testing

• Serum creatinine, BUN, complete metabolic panel to assess renal function 1, 3
• Complete urinalysis with microscopy examining for dysmorphic RBCs, casts, crystals, WBCs 1, 2
• Urine culture if infection suspected (preferably before antibiotics) 1, 3
• Voided urine cytology for high-risk patients to detect high-grade urothelial carcinomas 1, 2

Nephrology Evaluation (For Glomerular Source)

When glomerular indicators are present 1, 2:

• Quantify proteinuria using spot urine protein-to-creatinine ratio 1
• Complement levels (C3, C4) to evaluate for post-infectious glomerulonephritis or lupus nephritis 1
• Serologic testing: ANA, ANCA if vasculitis suspected 1
• Renal ultrasound to evaluate kidney size, echogenicity, and structural abnormalities 1
• Consider renal biopsy for definitive diagnosis of IgA nephropathy, Alport syndrome, or other glomerular diseases 3

Nephrology referral is indicated for: persistent significant proteinuria (protein-to-creatinine ratio >0.2 for three specimens), red cell casts or >80% dysmorphic RBCs, elevated/declining renal function, or hypertension with hematuria and proteinuria 1, 2

Follow-Up Protocol for Negative Initial Evaluation

If complete workup is negative but hematuria persists 1, 2:

• Repeat urinalysis at 6,12,24, and 36 months 1, 2
• Monitor blood pressure at each visit 1, 2
• Voided urine cytology at each visit for high-risk patients 1
• After two consecutive negative annual urinalyses, no further testing for asymptomatic microhematuria is necessary 1

Immediate Re-Evaluation Required If:

• Gross hematuria develops 1, 2
• Significant increase in degree of microscopic hematuria 1, 2
• New urologic symptoms appear (flank pain, dysuria, irritative voiding) 1, 2
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 1, 2

Pediatric Considerations

Children require a different approach 1, 3:

• Isolated microscopic hematuria without proteinuria or dysmorphic RBCs does NOT require imaging—clinical follow-up is sufficient 1, 3
• Gross hematuria in children requires renal and bladder ultrasound to exclude nephrolithiasis, anatomic abnormalities, and rarely tumors 1, 3
• CT is NOT appropriate for initial evaluation of isolated nonpainful, nontraumatic hematuria in children 1, 3
• Renal ultrasound is the preferred modality to assess kidney anatomy before potential renal biopsy 1, 3
• Common pediatric causes: glomerulonephritis, congenital anomalies, hypercalciuria 1, 3

Critical Pitfalls to Avoid

• Never defer evaluation due to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria themselves 1, 3, 2
• Never ignore gross hematuria even if self-limited—30-40% malignancy risk mandates urgent urologic referral 1, 3, 2
• Never rely solely on dipstick testing—confirm with microscopic urinalysis showing ≥3 RBCs/HPF 1, 2
• Never prescribe empiric antibiotics for hematuria without documented infection—this delays cancer diagnosis and provides false reassurance 1
• Never assume BPH explains hematuria—gross hematuria from BPH must be proven through appropriate evaluation and does not exclude concurrent malignancy 1
• Delays beyond 9 months from first hematuria presentation are associated with worse cancer-specific survival in bladder cancer patients 1