What is the next step in evaluating a patient with microscopic hematuria?

Microscopic Hematuria: Next Steps in Evaluation

Confirm True Microscopic Hematuria First

The first step is to confirm true microscopic hematuria by obtaining microscopic urinalysis showing ≥3 red blood cells per high-power field on at least two of three properly collected clean-catch midstream urine specimens. 1, 2 Dipstick testing alone has limited specificity (65-99%) and should never trigger extensive workup without microscopic confirmation. 2

• Do not proceed with imaging or invasive testing based solely on dipstick results. 3
• If a benign transient cause is suspected (menstruation, vigorous exercise, recent UTI), repeat urinalysis 48 hours after cessation of the cause or 6 weeks after completing UTI treatment. 2

Initial Evaluation Components

Once confirmed, perform these essential baseline assessments:

• Detailed history focusing on malignancy risk factors: age, sex, smoking history (quantify pack-years), occupational exposure to benzenes or aromatic amines, history of gross hematuria, irritative voiding symptoms, and history of pelvic irradiation. 1, 2
• Physical examination including blood pressure measurement to screen for hypertension suggesting glomerular disease. 1
• Serum creatinine to assess renal function and determine if nephrologic evaluation is needed. 1, 2
• Comprehensive urinalysis with sediment examination to assess RBC morphology (dysmorphic vs. normal), look for red cell casts (pathognomonic for glomerular disease), and evaluate for proteinuria. 1, 2

Determine Glomerular vs. Non-Glomerular Source

This distinction determines the entire subsequent pathway:

Glomerular indicators (refer to nephrology):

• Dysmorphic RBCs >80% 2, 3
• Red cell casts 1, 2
• Significant proteinuria (>500 mg/24 hours or protein-to-creatinine ratio >0.5) 1, 2
• Elevated serum creatinine 1
• Tea-colored or cola-colored urine 3

Non-glomerular source (proceed with urologic evaluation):

• Normal RBCs >80% 3
• Bright red blood 3
• Absence of proteinuria, casts, or dysmorphic RBCs 1

Risk Stratification for Non-Glomerular Hematuria

Use the 2025 AUA/SUFU risk stratification system to determine the intensity of urologic workup: 1

High-risk patients (malignancy risk 1.3%-6.3%): 1

• Age ≥60 years (men or women) 1, 2
• Smoking history >30 pack-years 1, 2

• 25 RBC/HPF on single urinalysis 2

• History of gross hematuria 1, 2
• Occupational exposure to chemicals/dyes 2

Intermediate-risk patients (malignancy risk 0.2%-3.1%): 1

• Women age 50-59 years or men age 40-59 years 2
• Smoking history 10-30 pack-years 2
• 11-25 RBC/HPF on single urinalysis 2

Low-risk patients (malignancy risk 0%-0.4%): 1

• Women age <50 years or men age <40 years 2
• Never smoker or <10 pack-years 2
• 3-10 RBC/HPF on single urinalysis 2
• No additional risk factors 2

Urologic Evaluation Based on Risk

For intermediate- and high-risk patients, perform both: 1

• Cystoscopy (flexible preferred) to visualize bladder mucosa, urethra, and ureteral orifices for transitional cell carcinoma. 1, 2, 3 Flexible cystoscopy causes less pain with equivalent or superior diagnostic accuracy compared to rigid cystoscopy. 3
• CT urography (multiphasic with unenhanced, nephrographic, and excretory phases) as the preferred imaging modality to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis. 1, 2, 3 This is superior to ultrasound or intravenous pyelography for comprehensive upper tract evaluation. 3

For low-risk patients: 2

• Shared decision-making regarding proceeding with full evaluation versus repeat urinalysis in 6 months. 2
• Many guidelines still recommend cystoscopy and imaging even for low-risk patients given the potential for missed malignancy. 1

Additional testing for high-risk patients:

• Voided urine cytology to detect high-grade urothelial carcinomas and carcinoma in situ. 2, 3

Critical Pitfalls to Avoid

• Never attribute hematuria to anticoagulation or antiplatelet therapy alone without completing full evaluation—these medications may unmask underlying pathology but do not cause hematuria themselves. 2, 3 Malignancy risk is similar regardless of anticoagulation status. 2
• Gross hematuria always requires urgent urologic referral with cystoscopy and imaging, even if self-limited, due to 30-40% malignancy risk. 2, 3
• Do not delay evaluation for recurrent UTIs—obtain urine culture, treat appropriately, then repeat urinalysis 6 weeks after treatment to confirm resolution. 2 Persistent hematuria after appropriate antibiotic therapy strongly suggests non-infectious etiology. 3
• Benign prostatic hyperplasia does not exclude concurrent malignancy—complete evaluation is still required. 3

Follow-Up for Negative Initial Evaluation

If all investigations are negative but hematuria persists:

• Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit. 1, 2
• 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: 2, 3
  • Gross hematuria develops
  • Significant increase in degree of microscopic hematuria
  • New urologic symptoms appear
  • Development of hypertension, proteinuria, or evidence of glomerular bleeding

When to Refer to Nephrology

Nephrology referral is indicated for: 1, 2

• Dysmorphic RBCs >80% with or without red cell casts
• Proteinuria >500 mg/24 hours (or protein-to-creatinine ratio >0.5)
• Elevated serum creatinine or declining renal function
• Hypertension accompanying hematuria and proteinuria
• Persistent hematuria with development of any glomerular features during follow-up