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

Evaluation and Management of Hematuria

Initial Confirmation and Classification

All patients with hematuria require microscopic confirmation showing ≥3 red blood cells per high-power field before initiating any workup—dipstick results alone are insufficient and should never trigger extensive evaluation. 1, 2

• Dipstick testing has limited specificity (65-99%) and produces false positives from myoglobin, hemoglobin, concentrated urine, or menstrual contamination 2, 3
• Confirm with microscopic urinalysis on a properly collected clean-catch midstream specimen 1, 2
• Distinguish between gross hematuria (visible blood) and microscopic hematuria (≥3 RBCs/HPF on microscopy) as this determines urgency of evaluation 4

Immediate Urologic Referral: Gross Hematuria

All patients with gross hematuria require immediate urologic referral for cystoscopy and upper tract imaging, even if the bleeding is self-limited or the patient is anticoagulated. 1, 2

• Gross hematuria carries 30-40% risk of malignancy, representing an odds ratio of 7.2 for urinary tract cancer 2, 4
• Never attribute gross hematuria to anticoagulation or antiplatelet therapy alone—these medications may unmask underlying pathology but do not cause hematuria 1, 2
• Anticoagulation status should not delay or prevent complete evaluation 1, 2

Exclude Benign Transient Causes

Before proceeding with extensive workup for microscopic hematuria, systematically exclude these reversible causes 2, 3:

• Urinary tract infection: Obtain urine culture; if positive, treat and repeat urinalysis 6 weeks after completing antibiotics to confirm resolution 2
• Menstruation: Repeat urinalysis 48 hours after cessation 2
• Vigorous exercise: Repeat urinalysis 48 hours after cessation 2, 4
• Recent sexual activity or trauma: Repeat urinalysis after 48 hours 2
• Viral illness: Consider deferring evaluation until resolution 1

Risk Stratification for Microscopic Hematuria

After confirming persistent microscopic hematuria (≥3 RBCs/HPF) and excluding benign causes, stratify patients by malignancy risk 2, 3:

High-Risk Features (Require Full Urologic Evaluation)

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

• 25 RBCs per high-power field 2

• History of gross hematuria 2, 3
• Occupational exposure to benzenes or aromatic amines (dyes, rubber, leather, paint industries) 1, 2
• History of pelvic irradiation 2
• Irritative voiding symptoms without infection 2, 4
• Analgesic abuse 2

Intermediate-Risk Features

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

Low-Risk Features

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

Determine Glomerular vs. Non-Glomerular Source

Examine urinary sediment for dysmorphic RBCs, red cell casts, and proteinuria to distinguish glomerular from urologic causes—this determines whether nephrology or urology referral is appropriate. 2, 3

Indicators of Glomerular Source (Nephrology Referral)

• >80% dysmorphic red blood cells 2, 3
• Red blood cell casts (pathognomonic for glomerular disease) 2, 3
• Significant proteinuria >500 mg/24 hours 2, 3
• Elevated serum creatinine or declining renal function 2, 3
• Tea-colored urine 4
• Associated hypertension 2, 3

Indicators of Non-Glomerular Source (Urology Referral)

• 80% normal (eumorphic) red blood cells 2

• Absence of proteinuria or minimal proteinuria 2
• Normal renal function 2
• Bright red blood or clots 4

Complete Urologic Evaluation for Non-Glomerular Hematuria

High-risk and intermediate-risk patients with non-glomerular microscopic hematuria require both cystoscopy and upper tract imaging to detect bladder cancer, renal cell carcinoma, and transitional cell carcinoma. 2, 3

Upper Tract Imaging

• Multiphasic CT urography is the preferred imaging modality for comprehensive evaluation of kidneys, ureters, and collecting system 2, 3
• CT urography detects renal cell carcinoma, transitional cell carcinoma, and urolithiasis with superior sensitivity 2, 4
• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation 4
• Consider radiation exposure risks in younger patients when weighing benefits of CT imaging 1

Lower Tract Evaluation

• Cystoscopy is mandatory for all patients ≥40 years with microscopic hematuria and all patients with gross hematuria regardless of age 2, 3
• Flexible cystoscopy causes less pain with equivalent or superior diagnostic accuracy compared to rigid cystoscopy 4
• Cystoscopy detects bladder tumors and carcinoma in situ that may be missed by imaging 2

Laboratory Testing

• Serum creatinine to assess renal function 2, 3
• Complete urinalysis with microscopic examination 2, 4
• Urine culture if infection suspected 2, 4
• Do NOT obtain urinary cytology or urine-based molecular markers in the initial evaluation—these add no value to the initial workup 1

Nephrology Referral Criteria

Refer to nephrology when glomerular disease is suspected 2, 3:

• Proteinuria >500 mg/24 hours (or protein-to-creatinine ratio >0.5) 2, 3

• 80% dysmorphic RBCs or red cell casts 2, 3

• Elevated serum creatinine or declining renal function 2, 3
• Persistent hematuria with development of hypertension 2, 3
• Family history of hereditary nephritis (Alport syndrome, thin basement membrane disease) 4

Follow-Up Protocol for Negative Initial Evaluation

If the complete urologic evaluation is negative but microscopic hematuria persists, repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit. 2, 3

• Monitor for development of hypertension, proteinuria, or evidence of glomerular bleeding 2, 3
• 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, 4
  • Gross hematuria develops
  • Significant increase in degree of microscopic hematuria occurs
  • New urologic symptoms appear (flank pain, irritative voiding symptoms, dysuria)
  • Development of hypertension, proteinuria, or declining renal function

Critical Pitfalls to Avoid

• Never screen asymptomatic adults with urinalysis for cancer detection—this leads to low-yield testing and unnecessary radiation exposure 1
• Never defer evaluation because the patient is anticoagulated—malignancy risk is identical regardless of anticoagulation status 1, 2
• Never attribute hematuria to benign prostatic hyperplasia without proving prostatic origin through appropriate evaluation—concurrent malignancy must be excluded 4
• Never rely on dipstick alone—confirm with microscopic examination showing ≥3 RBCs/HPF before initiating workup 1, 2
• Never obtain urinary cytology in the initial evaluation—it adds no value and increases costs without improving outcomes 1
• Never ignore gross hematuria even if self-limited—30-40% harbor malignancy and require urgent urologic referral 2, 4