What is the recommended evaluation and management for hematuria (blood in urine) without a urinary tract infection (UTI)?

Hematuria Without UTI: Evaluation and Management

Confirm True Hematuria First

Before initiating any workup, confirm microscopic hematuria with ≥3 red blood cells per high-power field on at least two of three properly collected clean-catch midstream urine specimens, as dipstick alone has limited specificity (65-99%) and can yield false positives from myoglobinuria, hemoglobinuria, or menstrual contamination. 1, 2

• Dipstick positivity alone should never trigger imaging or extensive investigation without microscopic confirmation 1
• Exclude transient benign causes before proceeding: menstruation, vigorous exercise (within 48 hours), sexual activity, recent viral illness, or trauma 2, 3

Distinguish Glomerular from Non-Glomerular Sources

Examine urinary sediment for dysmorphic RBCs and red cell casts to determine if nephrology or urology should lead the evaluation. 1, 2

Indicators of Glomerular Disease (Nephrology Referral):

• Dysmorphic RBCs >80% on urinary sediment 1, 2
• Red blood cell casts (pathognomonic for glomerular disease) 1, 3
• Significant proteinuria >500 mg/24 hours (or protein-to-creatinine ratio >0.5) 1, 2
• Elevated serum creatinine or declining renal function 1, 3
• Tea-colored urine appearance 1

Non-Glomerular Hematuria (Urologic Evaluation):

• Normal RBCs >80% on urinary sediment 1
• Minimal or no proteinuria 2
• Normal renal function 3

Risk Stratification for Urologic Malignancy

All patients with confirmed non-glomerular hematuria require risk stratification to determine evaluation intensity, with high-risk patients requiring full urologic evaluation including cystoscopy and imaging. 1, 2

High-Risk Features (Mandatory Full Evaluation):

• Age ≥60 years 1, 2, 3
• Smoking history >30 pack-years 1, 2

• 25 RBCs/HPF on single urinalysis 1, 2

• Any history of gross hematuria (even if self-limited) 1, 2
• Occupational exposure to chemicals/dyes (benzenes, aromatic amines) 1, 2, 3
• History of urologic disorders or pelvic irradiation 2, 3
• Irritative voiding symptoms 1, 2
• Recurrent UTIs despite appropriate antibiotics 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/HPF on single urinalysis 1

Low-Risk Features:

• Women age <50 years or men age <40 years 1, 3
• Never smoker or <10 pack-years 1, 2
• 3-10 RBCs/HPF on single urinalysis 1, 2

Complete Urologic Evaluation for High-Risk Patients

High-risk patients require both upper tract imaging and lower tract evaluation to detect malignancy, which accounts for 30-40% of gross hematuria cases and 2.6-4% of microscopic hematuria cases. 1

Upper Tract Imaging:

• Multiphasic CT urography is the preferred imaging modality for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis 4, 1, 2, 3
• Traditional intravenous urography (IVU) remains acceptable but has limited sensitivity for small renal masses 4
• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation 4

Lower Tract Evaluation:

• Cystoscopy is mandatory for all patients ≥40 years with microscopic hematuria to detect bladder tumors and carcinoma in situ 1, 2, 3
• Voided urine cytology is recommended for all high-risk patients, as urothelial cancers are the most commonly detected malignancies in hematuria 4, 1

Laboratory Testing:

• Serum creatinine to assess renal function 4, 3
• Complete urinalysis with microscopy 4, 1
• Urine culture if infection suspected 4, 3

Management of Low and Intermediate-Risk Patients

Intermediate-risk patients should undergo cystoscopy with urinary tract imaging through shared decision-making, while low-risk patients may undergo repeat urinalysis in 6 months or proceed with evaluation based on patient preference and clinical judgment. 2, 3

• Even low-risk patients warrant close monitoring, as approximately 3% of patients with microscopic hematuria harbor genitourinary malignancy 3
• Consider full evaluation in low-risk patients with patient anxiety or strong family history of urologic malignancy 2

Follow-Up Protocol After Negative Initial Evaluation

If the initial workup is negative but hematuria persists, repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit. 4, 2, 3

• Consider comprehensive re-evaluation in 3-5 years if hematuria persists or recurs, particularly in high-risk populations 2, 3
• Immediate re-evaluation is warranted if: gross hematuria develops, significant increase in degree of microscopic hematuria occurs, new urologic symptoms appear, or development of hypertension, proteinuria, or evidence of glomerular bleeding 4, 3
• Consider nephrology referral if hematuria persists with development of hypertension, proteinuria, or evidence of glomerular bleeding 4, 2

Critical Pitfalls to Avoid

Never attribute hematuria solely to anticoagulation or antiplatelet therapy without full evaluation, as these medications may unmask underlying pathology but do not cause hematuria themselves. 1, 2, 3

• Gross hematuria should never be ignored and requires urologic referral, even if self-limited 1
• Women are significantly underreferred for hematuria evaluation despite similar cancer risk as men 2
• Rapid recurrence of UTI with the same organism may indicate calculus disease and warrants imaging 2, 3
• Do not stop at symptom resolution alone; documented microscopic confirmation of resolution of hematuria is required 3