What tests should be ordered for a patient presenting with repeated hematuria (blood in urine)?

Evaluation of Repeated Blood in Urine

For patients with repeated microscopic hematuria, you must first confirm true hematuria with microscopic urinalysis (≥3 RBCs/HPF), exclude benign causes, then perform risk-stratified evaluation that includes cystoscopy and upper tract imaging based on the 2025 AUA/SUFU guidelines. 1

Initial Confirmation and Exclusion of Benign Causes

• Confirm microscopic hematuria with direct microscopic examination showing ≥3 red blood cells per high-power field on at least two of three properly collected urine specimens—never rely on dipstick alone 1, 2
• Exclude transient benign causes including menstruation, vigorous exercise within 48 hours, sexual activity, recent viral illness, trauma, and urinary tract infection 1, 2
• If UTI is suspected, obtain urine culture and treat appropriately, then repeat urinalysis 6 weeks after completing antibiotics to confirm resolution 2, 3
• Measure blood pressure and serum creatinine at initial evaluation to assess for renal parenchymal disease 1

Assessment for Glomerular Disease

Before proceeding with urologic evaluation, determine if the hematuria has a glomerular origin:

• Examine urinary sediment for dysmorphic red blood cells (>80% suggests glomerular source) and red cell casts (virtually pathognomonic for glomerular bleeding) 1, 2
• Quantify proteinuria with 24-hour urine collection if dipstick shows ≥1+ protein; >1,000 mg/24 hours strongly suggests renal parenchymal disease and warrants nephrology referral 1, 2
• Refer to nephrology if any of the following are present: red cell casts, >80% dysmorphic RBCs, proteinuria >500 mg/24 hours (especially if increasing), or elevated serum creatinine 1, 3

Risk Stratification for Urologic Evaluation

If glomerular disease is excluded, stratify patients using the 2025 AUA/SUFU system based on three key factors: age, smoking history, and degree of hematuria 1:

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

• All criteria must be met: Women <60 years OR men <40 years, never smoker or <10 pack-years, and 3-10 RBCs/HPF 1, 4
• Management: Repeat urinalysis in 6 months; if persistent, engage in shared decision-making about proceeding with cystoscopy and imaging 4

Intermediate Risk (0.2%-3.1% malignancy risk)

• One or more criteria: Women ≥60 years OR men 40-59 years, 10-30 pack-years smoking, or 11-25 RBCs/HPF 1, 4
• Management: Cystoscopy with urinary tract imaging recommended through shared decision-making 1, 4

High Risk (1.3%-6.3% malignancy risk)

• One or more criteria: Men ≥60 years, >30 pack-years smoking, >25 RBCs/HPF, or history of gross hematuria with no prior evaluation 1, 4
• Additional high-risk features: Occupational exposure to benzenes or aromatic amines, history of pelvic irradiation, analgesic abuse, irritative voiding symptoms, recurrent UTIs despite appropriate antibiotics, or family history of Lynch syndrome 1, 2
• Management: Mandatory cystoscopy and upper tract imaging 1, 4

Specific Diagnostic Tests Required

For All Patients Undergoing Urologic Evaluation:

• Cystoscopy is mandatory for detecting bladder cancer and carcinoma in situ—most cancers in hematuria patients are bladder cancers best detected by cystoscopy 1, 3
• Upper tract imaging with CT urography (preferred) or MR urography to detect upper tract urothelial carcinoma and renal cell carcinoma 1, 3
• Serum creatinine to assess renal function 1

Tests NOT Recommended:

• Do not routinely use urine cytology or urine-based tumor markers to decide whether to perform cystoscopy in initial evaluation—these have poor sensitivity (57.7%) and do not change management 1
• Do not use cytology as an adjunctive test after normal cystoscopy 1

Critical Pitfalls to Avoid

• Never attribute hematuria solely to anticoagulation or antiplatelet therapy—these patients require identical evaluation as non-anticoagulated patients 2, 4
• Do not skip upper tract imaging if urologic evaluation is indicated—cystoscopy alone misses upper tract malignancies 4
• History of gross hematuria elevates risk significantly (odds ratio 7.2) even if current presentation is microscopic hematuria 2
• Delays in bladder cancer diagnosis contribute to 34% increased cancer-specific mortality 1

Follow-Up After Negative Initial Evaluation

• If evaluation is completely negative but hematuria persists: Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit 2, 3
• Consider repeat cystoscopy and imaging within 3-5 years for persistent or recurrent hematuria, particularly in high-risk populations 2
• Immediate re-evaluation is warranted if gross hematuria develops, significant increase in degree of microscopic hematuria occurs, or new urologic symptoms appear 2, 4
• Most patients with negative risk-stratified evaluation can be safely discharged after shared decision-making, as repeat evaluation yields low malignancy detection (1.2% bladder cancer, 1.3% renal mass) 1, 5

Special Considerations

• Patients with family history of Lynch syndrome warrant upper tract imaging regardless of risk classification, preferably with CT or MR urography 1
• If benign etiology is found (enlarged prostate, non-obstructing stones, pelvic organ prolapse) and hematuria remains stable, engage in shared decision-making about further evaluation based on time since initial evaluation and overall risk factors 1