Blood in Urine Without Infection: Diagnostic and Management Approach
All patients with confirmed hematuria (≥3 RBCs per high-power field) without infection require risk stratification followed by appropriate urologic evaluation, with high-risk patients needing both cystoscopy and upper tract imaging to exclude malignancy. 1, 2
Initial Confirmation and Exclusion of Benign Causes
Confirm true hematuria with microscopic urinalysis showing ≥3 red blood cells per high-power field on at least two of three properly collected clean-catch midstream specimens—dipstick positivity alone is insufficient 1, 2
Exclude transient benign causes by repeating urinalysis 48 hours after cessation of: vigorous exercise, menstruation, sexual activity, recent trauma, or viral illness 1, 3
Rule out urinary tract infection with urine culture; if positive, treat appropriately and repeat urinalysis 6 weeks after completing antibiotics to confirm resolution of hematuria 1
Never attribute hematuria solely to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria, and evaluation should proceed identically 1, 3
Determine Source: Glomerular vs Non-Glomerular
Examine urinary sediment for dysmorphic red blood cells (>80% suggests glomerular source), red cell casts (pathognomonic for glomerular disease), and degree of proteinuria 1, 2
Glomerular indicators include: tea-colored urine, significant proteinuria (>500 mg/24 hours), red cell casts, dysmorphic RBCs >80%, and elevated serum creatinine 1, 3
Measure serum creatinine to assess renal function in all patients 1, 2
Refer to nephrology if glomerular source is suspected (red cell casts, >80% dysmorphic RBCs, proteinuria >500 mg/24 hours, elevated creatinine, or associated hypertension) 1, 2
Risk Stratification for Urologic Evaluation
The American Urological Association provides clear risk categories that determine the intensity of evaluation 1:
High-Risk Features (Require Full Urologic Workup)
- Age ≥60 years 1
- Smoking history >30 pack-years 1
25 RBCs per high-power field 1
- History of gross hematuria 1
- Occupational exposure to chemicals/dyes (benzenes, aromatic amines) 1
- History of pelvic irradiation 1
- Irritative voiding symptoms 1
Intermediate-Risk Features
- Women age 50-59 years or men age 40-59 years 1
- Smoking history 10-30 pack-years 1
- 11-25 RBCs per high-power field 1
Low-Risk Features
- Women age <50 years or men age <40 years 1
- Never smoker or <10 pack-years 1
- 3-10 RBCs per high-power field on single urinalysis 1
Complete Urologic Evaluation for Non-Glomerular Hematuria
High-Risk Patients
Multiphasic CT urography is the preferred imaging modality for comprehensive upper tract evaluation to detect urothelial carcinomas, renal cell carcinomas, and stones 1, 2
Cystoscopy is mandatory for all patients ≥40 years old and younger patients with risk factors to detect bladder tumors and carcinoma in situ 1, 2
Urine cytology should be performed in high-risk patients to detect urothelial cancers 2
Intermediate-Risk Patients
- Shared decision-making regarding cystoscopy with urinary tract imaging is appropriate 1
Low-Risk Patients
- May undergo repeat urinalysis in 6 months or proceed with evaluation based on patient preference 1
Gross (Visible) Hematuria
Gross hematuria requires immediate urologic referral regardless of other factors, as malignancy risk is 30-40%. 3, 2
Never delay evaluation even if gross hematuria is self-limited or occurs in the setting of anticoagulation 1, 3
Gross hematuria significantly increases cancer risk (odds ratio 7.2) and should not be attributed to benign causes without complete evaluation 1
Follow-Up Protocol After Negative Initial Evaluation
Repeat urinalysis at 6,12,24, and 36 months for patients with persistent hematuria after negative workup 1, 2
Consider repeat cystoscopy and imaging within 3-5 years for persistent or recurrent hematuria, particularly in high-risk populations 1
Immediate re-evaluation is warranted if gross hematuria develops, significant increase in degree of microscopic hematuria occurs, or new urologic symptoms appear 1
Nephrology referral if hematuria persists with development of hypertension, proteinuria, or evidence of glomerular bleeding 1, 2
Critical Pitfalls to Avoid
Do not stop at symptom resolution alone—documented microscopic confirmation of resolution of hematuria is required 1
Approximately 3% of patients with microscopic hematuria harbor genitourinary malignancy, and this risk increases substantially with specific risk factors 1
Patients on anticoagulation should be evaluated identically to non-anticoagulated patients, as malignancy risk is similar regardless of anticoagulation status 1
Do not delay evaluation in patients with rapid recurrence of UTI with the same organism, as this may warrant imaging to rule out calculus, particularly with struvite stone-forming bacteria like P. mirabilis 1