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 only 65-99% specificity and produces false positives. 1

Initial Confirmation and Documentation

• Verify true hematuria by obtaining microscopic urinalysis demonstrating ≥3 RBCs/HPF on two of three specimens—dipstick positivity alone is insufficient to trigger full evaluation 1, 2
• Document whether hematuria is gross (visible) or microscopic (only detected under microscope), as gross hematuria carries a 30-40% malignancy risk versus 0.5-5% for microscopic hematuria 1, 3
• Exclude menstrual contamination in women and confirm proper specimen collection technique 1

Risk Stratification for Malignancy

Once confirmed, stratify patients using the AUA/SUFU 2025 risk classification system based on age, sex, smoking history, and degree of hematuria: 2

High-Risk Features (1.3-6.3% malignancy risk):

• Males ≥60 years or females ≥60 years 1, 4
• Smoking history >30 pack-years 1, 4
• Any history of gross hematuria 1, 4

• 25 RBCs/HPF 1

• Occupational exposure to benzenes or aromatic amines 1, 4
• Irritative voiding symptoms without infection 1, 4

Intermediate-Risk Features (0.2-3.1% malignancy risk):

• Males 40-59 years 1
• Females <60 years 1
• Smoking history 10-30 pack-years 1
• 11-25 RBCs/HPF 1

Low-Risk Features (0%-0.4% malignancy risk):

• Males <40 years 1
• Never smoker or <10 pack-years 1
• 3-10 RBCs/HPF 1

Distinguish Glomerular from Non-Glomerular Source

Before proceeding with urologic workup, determine if hematuria originates from glomerular disease, which requires nephrology referral instead: 1, 2

Features Suggesting Glomerular Source:

• >80% dysmorphic RBCs on phase-contrast microscopy 1, 4
• Red blood cell casts (pathognomonic for glomerular disease) 1, 4
• Tea-colored or cola-colored urine 1, 4
• Significant proteinuria (protein-to-creatinine ratio >0.2 g/g) 1, 4
• Elevated creatinine or declining renal function 1
• Hypertension accompanying hematuria 1

Features Suggesting Non-Glomerular (Urologic) Source:

• >80% normal (eumorphic) RBCs 1, 4
• Bright red blood in urine 1
• Flank pain, suprapubic pain, or dysuria 1
• Clots in urine 1

Complete Urologic Evaluation for Non-Glomerular Hematuria

For ALL Gross Hematuria (Regardless of Risk):

Gross hematuria mandates urgent and complete urologic evaluation with both upper and lower tract imaging, even if self-limited, due to 30-40% malignancy risk: 1, 3

1. Multiphasic CT urography (unenhanced, nephrographic, and excretory phases) to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1, 2
2. Cystoscopy (flexible preferred over rigid for less pain and equivalent accuracy) to visualize bladder mucosa, urethra, and ureteral orifices 1, 2
3. Voided urine cytology in high-risk patients to detect high-grade urothelial carcinomas 1
4. Serum creatinine to assess renal function 1, 2

For Microscopic Hematuria (Risk-Stratified):

High-Risk Patients:

• Complete urologic evaluation identical to gross hematuria protocol above 1, 2
• Cystoscopy and CT urography are both mandatory 1, 2

Intermediate-Risk Patients:

• Shared decision-making regarding cystoscopy and CT urography 1, 2
• Most should undergo complete evaluation given 0.2-3.1% malignancy risk 2

Low-Risk Patients:

• May defer cystoscopy and imaging if no other risk factors present 1, 2
• However, if any benign cause is not identified, proceed with complete evaluation 1

Laboratory Evaluation

Obtain the following labs for all patients with confirmed hematuria: 1, 2

• Complete urinalysis with microscopic sediment examination 1, 2
• Serum creatinine, BUN, and complete metabolic panel 1
• Urine culture if infection suspected (obtain BEFORE antibiotics) 1, 4
• Complete blood count with platelets to evaluate for coagulopathy 1

If glomerular source suspected, add: 1

• Spot urine protein-to-creatinine ratio 1
• Complement levels (C3, C4) 1
• ANA and ANCA if vasculitis suspected 1

Special Populations and Considerations

Pediatric Patients:

• Children with isolated microscopic hematuria without proteinuria or dysmorphic RBCs do NOT require imaging—only clinical follow-up 1, 5
• For gross hematuria in children, obtain urine culture, urine calcium-to-creatinine ratio, and renal ultrasound (NOT CT) 1, 5
• Glomerulonephritis and congenital anomalies are most common causes in children 1, 4

Patients on Anticoagulation:

• Never defer evaluation due to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria themselves 1, 4, 2
• Proceed with full evaluation regardless of medication use 1, 4

Patients with Suspected UTI:

• Obtain urine culture BEFORE starting antibiotics 1, 4
• If hematuria persists >2 months despite appropriate antibiotic therapy, this effectively rules out simple UTI and mandates complete urologic evaluation 1
• Never prescribe additional antibiotics for persistent hematuria without completing cancer workup 1

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
• After two consecutive negative annual urinalyses, no further testing needed 1

Immediate re-evaluation warranted if: 1, 2

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

Nephrology Referral Indications

Refer to nephrology if: 1, 2

• Persistent significant proteinuria (protein-to-creatinine ratio >0.2 g/g) 1
• Presence of red cell casts or >80% dysmorphic RBCs 1, 4
• Elevated creatinine or declining renal function 1
• Hypertension with hematuria and proteinuria 1
• Hematuria persists with development of any glomerular features 1, 2

Critical Pitfalls to Avoid

• Never ignore gross hematuria, even if self-limited—30-40% malignancy risk mandates urgent urologic referral 1, 3
• Never attribute hematuria to anticoagulation alone—complete evaluation required regardless 1, 4
• Never rely on dipstick alone—confirm with microscopic urinalysis showing ≥3 RBCs/HPF 1, 2
• Never treat asymptomatic bacteriuria with pyuria and hematuria—hematuria requires urologic evaluation, not antibiotics 1
• Never defer workup in elderly males with gross hematuria—this population has highest malignancy risk and requires immediate cystoscopy and CT urography 1