What is the appropriate evaluation and treatment for hematuria (blood in the urine)?

Evaluation and Management of Hematuria

Initial Confirmation and Classification

All hematuria requires microscopic confirmation with ≥3 red blood cells per high-power field before initiating any workup, as dipstick testing alone has limited specificity (65-99%) and produces false positives from myoglobinuria, hemoglobinuria, or menstrual contamination. 1

Distinguish Gross from Microscopic Hematuria

• Gross hematuria (visible blood) mandates immediate urologic referral regardless of whether it is self-limited or persistent, as it carries a 30-40% risk of malignancy. 2, 3
• Microscopic hematuria (≥3 RBCs/HPF on microscopy) requires risk stratification before determining the evaluation pathway 1
• Never attribute hematuria solely to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria themselves 1, 4

Exclude Transient Benign Causes First

Before proceeding with extensive evaluation, systematically exclude:

• Menstruation, vigorous exercise, sexual activity, viral illness, or recent trauma 1
• Urinary tract infection: obtain urine culture before starting antibiotics, treat appropriately, then repeat urinalysis 6 weeks after treatment completion to confirm resolution 1, 4
• If a benign cause is suspected, repeat urinalysis 48 hours after cessation of the potential cause 4

Risk Stratification for Urologic Malignancy

The American Urological Association provides a three-tier risk stratification system that determines evaluation intensity:

Low-Risk Patients

• Women age <60 years OR men age <40 years
• Never smokers or <10 pack-years smoking history
• 3-10 RBCs/HPF on single urinalysis
• No additional risk factors 1

High-Risk Patients (Require Full Evaluation)

• Age ≥60 years

• 30 pack-years smoking history

• 25 RBCs/HPF on single urinalysis

• History of gross hematuria
• Occupational exposure to chemicals/dyes (benzenes, aromatic amines)
• History of urologic disorders
• Irritative voiding symptoms
• Recurrent UTIs despite appropriate antibiotics 1, 4

Intermediate-Risk Patients

• Women age 50-59 years OR men age 40-59 years
• 10-30 pack-years smoking history
• 11-25 RBCs/HPF 4

Determine Glomerular vs. Non-Glomerular Source

Before pursuing urologic evaluation, assess for indicators of glomerular disease to avoid unnecessary invasive testing:

Glomerular Source Indicators

• Dysmorphic RBCs >80% on urinary sediment examination
• Red blood cell casts (pathognomonic for glomerular disease)
• Significant proteinuria >500 mg/24 hours
• Elevated serum creatinine
• Tea-colored urine 1, 3, 4

Nephrology Referral Criteria

• Refer to nephrology if proteinuria >1,000 mg/24 hours, dysmorphic RBCs >80% with red cell casts, elevated creatinine, or associated hypertension 1, 4
• Proteinuria >500 mg/24 hours, particularly if increasing or persistent 4

Urologic Evaluation for Non-Glomerular Hematuria

High-Risk Patients (Mandatory Full Evaluation)

• Multiphasic CT urography is the preferred imaging modality for upper tract evaluation to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1, 3
• Cystoscopy is mandatory for all patients ≥40 years with microscopic hematuria to detect bladder tumors and carcinoma in situ 1, 4
• Urine cytology in high-risk patients to detect urothelial cancers 1
• Serum creatinine to assess renal function 3

Intermediate-Risk Patients

• Cystoscopy with urinary tract imaging through shared decision-making 4

Low-Risk Patients

• May undergo repeat urinalysis in 6 months or proceed with evaluation based on patient preference and shared decision-making 4

Critical Imaging Considerations

• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation 3
• CT urography provides superior detection of small renal masses compared to traditional intravenous urography 3
• Consider radiation exposure risks in younger patients when selecting imaging modality, as CT carries potential carcinogenesis risk 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 1, 3
• Consider comprehensive re-evaluation in 3-5 years if hematuria persists or recurs, particularly in high-risk populations 1, 4

Triggers for Immediate Re-Evaluation

• Development of gross hematuria
• Significant increase in degree of microscopic hematuria
• New urologic symptoms (irritative voiding, flank pain, dysuria)
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 3, 4

Critical Pitfalls to Avoid

• Never defer evaluation in patients on anticoagulation or antiplatelet therapy—malignancy risk is similar regardless of anticoagulation status 1, 4
• Do not delay evaluation in patients with rapid recurrence of UTI with the same organism, as this may indicate calculus disease 1
• Do not obtain urinary cytology or other urine-based molecular markers for bladder cancer detection in the initial evaluation of hematuria 2
• Do not use screening urinalysis for cancer detection in asymptomatic adults 2
• Maintain equal vigilance across sexes—women are significantly underreferred for hematuria evaluation despite similar cancer risk 1
• Do not stop at symptom resolution alone; documented microscopic confirmation of resolution of hematuria is required 4