What is the initial workup for a patient presenting with hematuria (blood in urine)?

Initial Workup for Hematuria

The initial workup for hematuria requires confirmation with microscopic urinalysis showing ≥3 RBCs per high-power field on at least two of three properly collected specimens, followed by urinalysis with microscopy, renal function testing, risk stratification, and appropriate imaging (CT urography for high-risk patients) plus cystoscopy based on risk factors. 1

Confirm True Hematuria First

• Never proceed with extensive workup based on dipstick alone—dipstick tests have only 65-99% specificity and produce false positives from myoglobin, hemoglobin, menstrual contamination, or vigorous exercise 1, 2
• Obtain microscopic urinalysis on at least two of three properly collected clean-catch midstream specimens to confirm ≥3 RBCs per high-power field 1
• If only 0-2 RBCs/HPF are found, this is within normal limits and does not warrant urologic workup 2

Rule Out Benign Transient Causes

Before proceeding with extensive evaluation, exclude:

• Urinary tract infection—obtain urine culture before antibiotics if infection suspected 1, 2
• Menstruation—repeat urinalysis when not menstruating 1, 2
• Vigorous exercise—repeat after 48-72 hours of rest 1, 2
• Recent sexual activity or trauma—repeat urinalysis after resolution 1

Critical pitfall: Even if benign causes are identified, patients with risk factors still require full evaluation, as these conditions may unmask underlying pathology 1, 2

Perform Initial Laboratory Assessment

• Complete urinalysis with microscopic examination assessing: 1
  • Number of RBCs per high-power field
  • RBC morphology (dysmorphic vs. normal-shaped)
  • Presence of red cell casts (pathognomonic for glomerular disease)
  • Degree of proteinuria
  • White blood cells and bacteria
• Serum creatinine to assess renal function 1
• Urine protein-to-creatinine ratio if proteinuria detected (normal <0.2 g/g) 2

Determine Source: Glomerular vs. Non-Glomerular

Glomerular source indicators (nephrology referral needed): 1, 2, 3

• 80% dysmorphic red blood cells on phase-contrast microscopy

• Red blood cell casts in urinary sediment
• Significant proteinuria (protein-to-creatinine ratio >0.3)
• Elevated serum creatinine
• Tea-colored urine

Non-glomerular (urologic) source indicators (urology referral needed): 1, 3

• 80% normal-shaped (isomorphic) RBCs

• Minimal or no proteinuria
• Normal serum creatinine
• Bright red blood or clots

Risk Stratification for Malignancy

High-risk patients (require urgent urologic referral): 1, 2, 3

• Any gross hematuria (30-40% malignancy risk, even if self-limited)
• Men ≥60 years
• Smoking history >30 pack-years

• 25 RBCs per high-power field

• Occupational exposure to chemicals/dyes (benzenes, aromatic amines)
• History of pelvic irradiation
• History of urologic disorders or chronic irritative voiding symptoms

Intermediate-risk patients: 2, 3

• Men 40-59 years or women ≥60 years
• 11-25 RBCs per high-power field
• Smoking history 10-30 pack-years

Low-risk patients: 2, 3

• Men <40 years and women <60 years
• 3-10 RBCs per high-power field
• Never smokers or <10 pack-years

Imaging Based on Risk Level

For high-risk or intermediate-risk patients with non-glomerular hematuria: 1, 2

• Multiphasic CT urography is the preferred imaging modality for comprehensive upper tract evaluation, detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis

For low-risk patients or children: 1, 3

• Renal and bladder ultrasound is appropriate first-line imaging
• Children with isolated microscopic hematuria without proteinuria, trauma, or concerning features rarely require imaging 3

For suspected glomerular disease: 2

• Renal ultrasound to evaluate kidney size, echogenicity, and structural abnormalities

Cystoscopy Indications

Mandatory cystoscopy for: 1, 2

• All patients with gross hematuria
• All patients ≥40 years with microscopic hematuria
• Patients <40 years with risk factors for bladder cancer (smoking, occupational exposures, irritative voiding symptoms)
• Intermediate- and high-risk patients by AUA/SUFU stratification

Flexible cystoscopy is preferred over rigid cystoscopy due to less pain, fewer post-procedure symptoms, and equivalent diagnostic accuracy 1, 2

Specialist Referral Pathways

Immediate urology referral for: 1, 2

• Any gross hematuria (do not delay while waiting for other test results)
• Microscopic hematuria with risk factors for malignancy
• Persistent unexplained microscopic hematuria after negative initial workup

Nephrology referral for: 1, 2

• Red blood cell casts or >80% dysmorphic RBCs
• Significant proteinuria (protein-to-creatinine ratio >0.2 on three specimens)
• Elevated creatinine or declining renal function
• Hypertension with hematuria and proteinuria

Follow-Up for Negative Initial Evaluation

If initial workup is negative but microscopic hematuria persists: 1, 2

• Repeat urinalysis, blood pressure, and consider urine cytology at 6,12,24, and 36 months
• Immediate re-evaluation if: gross hematuria develops, significant increase in degree of microscopic hematuria, new urologic symptoms, or development of hypertension/proteinuria/glomerular bleeding indicators

Critical Pitfalls to Avoid

• Never attribute hematuria solely to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology and do not justify deferring evaluation 1, 2, 3
• Never assume BPH or hypertension explains hematuria without proper evaluation—concurrent malignancy must be excluded 1, 2
• Never delay urologic referral for gross hematuria even if bleeding resolves spontaneously—30-40% malignancy risk persists 1, 2, 3
• Never rely solely on dipstick results without microscopic confirmation 1
• Never use urine cytology or molecular markers (NMP22, BTA stat) in initial evaluation of asymptomatic microscopic hematuria—these are not first-line tests 3