What investigations should be performed for hematuria?

Hematuria Investigation Algorithm

All patients with hematuria require risk stratification using the 2025 AUA/SUFU system, followed by history/physical examination, urinalysis with microscopy, serum creatinine, and then risk-appropriate imaging (CT urography for high-risk, ultrasound kidneys for intermediate-risk) plus cystoscopy for intermediate and high-risk patients. 1

Initial Workup (All Patients)

Before any imaging, perform these baseline investigations:

• Urinalysis with microscopy - Confirm hematuria (≥3 RBCs/HPF on properly collected, non-contaminated specimen without infection) 2
• History and physical examination including:
  • Detailed smoking history (pack-years calculation)
  • Occupational/environmental chemical exposures
  • Family history of urologic malignancies
  • History of gross hematuria episodes
  • Irritative voiding symptoms
  • Prior pelvic irradiation or chemotherapy exposure
  • Blood pressure measurement 1
• Serum creatinine - Assess for renal parenchymal disease 1
• Urine culture if infection suspected (before antibiotics if possible) 2

Risk Stratification (2025 AUA/SUFU System)

Classify patients into risk categories based on all of the following criteria 1:

Low/Negligible Risk (0-0.4% malignancy risk)

Must meet ALL criteria:

• 3-10 RBC/HPF
• Women <60 years OR men <40 years
• Never smoker or <10 pack-years
• No additional urothelial cancer risk factors

Intermediate Risk (0.2-3.1% malignancy risk)

One or more of:

• 11-25 RBC/HPF
• Women ≥60 years OR men 40-59 years
• 10-30 pack-years smoking
• Any additional urothelial cancer risk factors

High Risk (1.3-6.3% malignancy risk)

One or more of:

• 25 RBC/HPF

• Men ≥60 years

• 30 pack-years smoking

• One or more risk factors PLUS any high-risk feature

Critical caveat: History of gross hematuria with no prior evaluation automatically upgrades a previously low-risk patient to intermediate/high-risk if repeat urinalysis shows 3-25 RBC/HPF 1.

Risk-Appropriate Imaging

Gross Hematuria (30-40% malignancy risk)

• CT urography (usually appropriate) - includes unenhanced phase, nephrographic phase, and excretory phase (≥5 minutes post-contrast) with thin-slice acquisition 2
• This is the single most comprehensive study for evaluating the entire urinary tract 2

High-Risk Microhematuria

• CT urography (preferred) 1, 2
• MR urography may be considered as alternative if CT contraindicated 2

Intermediate-Risk Microhematuria

• Ultrasound kidneys (first-line) 1
• Consider CT urography if ultrasound inadequate or abnormal

Low-Risk Microhematuria

• No routine imaging recommended 2
• Shared decision-making regarding repeat urinalysis versus proceeding to evaluation 1

Important distinction: The 2025 AUA guidelines effectively stratify for urothelial cancer risk but do NOT predict renal cortical neoplasms, which occur at similar rates across all risk groups 3. This suggests imaging goals should focus primarily on urothelial cancer detection.

Cystoscopy Indications

• Mandatory for gross hematuria - all patients 2
• Recommended for intermediate and high-risk microhematuria 1
• Not routinely needed for low-risk microhematuria 1

Critical point: Most cancers in hematuria patients are bladder cancers, optimally detected by cystoscopy, not imaging alone. Underuse of cystoscopy contributes to diagnostic delays associated with 34% increased cancer-specific mortality 1.

Special Populations

Pregnancy

• Ultrasound kidneys (first-line) 2
• Consider CT or MR urography after delivery if indicated 2

Anticoagulation

• Proceed with full evaluation - anticoagulation does NOT alter the workup 2

Suspected Renal Parenchymal Disease

• Concurrent nephrology evaluation indicated
• Does NOT preclude urologic evaluation for malignancy 2

When to Defer Complete Workup

Patients with identified benign causes and no risk factors may defer imaging 2:

• Vigorous exercise
• Confirmed urinary tract infection (recheck urinalysis after treatment)
• Menstruation
• Recent urologic procedure
• Trauma

However, if hematuria persists after treating the presumed benign cause, proceed with full risk-appropriate evaluation 2.

Evidence Strength Considerations

The 2025 AUA/SUFU guideline 1 represents the most current evidence-based approach and supersedes the 2020 ACR recommendations 2. Recent validation studies confirm this risk stratification effectively predicts urothelial malignancy 3, 4, with high-risk patients having 6.3% bladder cancer incidence versus 0.4% in low-risk patients 4.

Key pitfall: Women over 70 years have 2.2% bladder cancer incidence 3, suggesting the current guideline may underestimate risk in older women by not classifying them as high-risk based on age alone (unlike men ≥60 years).