What is the appropriate evaluation and treatment for a patient presenting with hematuria (presence of blood in the urine)?

Evaluation and Management of Red Urine (Hematuria)

Confirm true hematuria with microscopic urinalysis showing ≥3 red blood cells per high-power field before initiating any workup, as dipstick tests alone have only 65-99% specificity and can produce false positives. 1

Initial Confirmation and Benign Cause Exclusion

• Verify microscopic hematuria on at least two of three properly collected clean-catch midstream urine specimens before proceeding with extensive evaluation 1, 2
• Exclude benign causes first: menstruation, vigorous exercise, sexual activity, viral illness, trauma, and urinary tract infection 1, 3
• If UTI is suspected, obtain urine culture before antibiotics, treat appropriately, and repeat urinalysis 6 weeks after treatment completion to confirm resolution 3
• For suspected benign causes (exercise, menstruation), repeat urinalysis 48 hours after cessation of the trigger 3

Critical pitfall: Never attribute hematuria to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria themselves, and evaluation must proceed regardless 2, 3

Risk Stratification for Malignancy

Once true hematuria is confirmed, stratify patients by risk factors:

High-Risk Features (Require Full Urologic Evaluation):

• Age ≥60 years (males) or ≥60 years (females) 2
• Smoking history >30 pack-years 2
• History of gross hematuria (30-40% malignancy risk) 2, 3
• Occupational exposure to chemicals/dyes (benzenes, aromatic amines) 1, 2
• Irritative voiding symptoms without infection 1, 2

• 25 RBCs per high-power field 3

Intermediate-Risk Features:

• Males age 40-59 years or females age 50-59 years 3
• Smoking history 10-30 pack-years 3
• 11-25 RBCs per high-power field 3

Low-Risk Features:

• Males <40 years or females <50 years 3
• Never smoker or <10 pack-years 3
• 3-10 RBCs per high-power field 3

Determine Glomerular vs. Non-Glomerular Source

Examine urinary sediment for dysmorphic RBCs and red cell casts to distinguish the source:

Glomerular Source Indicators:

• 80% dysmorphic red blood cells 1

• Red cell casts (pathognomonic for glomerular disease) 1
• Significant proteinuria (>500 mg/24 hours) 1
• Elevated serum creatinine 1
• Tea-colored or cola-colored urine 2

Non-Glomerular (Urologic) Source Indicators:

• 80% normal-shaped RBCs 1

• Minimal proteinuria (<500 mg/24 hours) 1
• Normal serum creatinine 1
• Bright red blood 2

Complete Urologic Evaluation (Non-Glomerular Source)

For high-risk patients or any gross hematuria, proceed with complete urologic evaluation:

Upper Tract Imaging:

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

Lower Tract Evaluation:

• Cystoscopy is mandatory for all patients with gross hematuria and high-risk microscopic hematuria to evaluate for bladder transitional cell carcinoma 1, 2
• Flexible cystoscopy is preferred over rigid cystoscopy (less pain, equivalent diagnostic accuracy) 2

Laboratory Testing:

• Serum creatinine to assess renal function 1, 2
• Complete urinalysis with microscopy 2
• Urine culture if infection suspected 2, 3
• Voided urine cytology in high-risk patients (age >60, smoking history) 2

Nephrology Referral (Glomerular Source)

Refer to nephrology if:

• Proteinuria >1,000 mg/24 hours 1
• Proteinuria >500 mg/24 hours that is persistent or increasing 1
• Red cell casts present 1
• Predominantly dysmorphic RBCs (>80%) 1
• Elevated creatinine or declining renal function 3
• Hypertension with hematuria and proteinuria 3

Nephrology evaluation may include assessment for systemic diseases, consideration of renal biopsy, and comprehensive renal function assessment 1

Follow-Up Protocol for Negative Initial Evaluation

If initial workup is negative but hematuria persists:

• Repeat urinalysis at 6,12,24, and 36 months 1, 2
• Monitor blood pressure at each visit 1, 2
• Consider repeat cystoscopy and imaging within 3-5 years for persistent hematuria, particularly in high-risk populations 3

Immediate re-evaluation is warranted if:

• Gross hematuria develops 2, 3
• Significant increase in degree of microscopic hematuria 2, 3
• New urologic symptoms appear 2, 3
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 1, 2

Special Considerations

Gross hematuria requires urgent urologic referral even if self-limited due to 30-40% malignancy risk 2, 3

For intermediate-risk patients, shared decision-making regarding cystoscopy and imaging is appropriate 3

Low-risk patients may undergo repeat urinalysis in 6 months or proceed with evaluation based on patient preference and clinical judgment 3

Common pitfall: Hematuria can precede bladder cancer diagnosis by many years, making long-term surveillance essential in high-risk elderly patients 2