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

Workup for Hematuria

Initial Confirmation and Classification

Confirm true hematuria with microscopic urinalysis showing ≥3 red blood cells per high-power field (RBC/HPF) on at least two of three properly collected clean-catch midstream urine specimens before initiating any workup. 1 Dipstick tests have only 65-99% specificity and can produce false positives from myoglobin, hemoglobin, or menstrual contamination. 1

Distinguish Gross vs. Microscopic Hematuria

• Gross (macroscopic) hematuria is visible blood in urine and carries a 30-40% risk of malignancy, requiring urgent urologic evaluation regardless of whether it is self-limited. 1, 2
• Microscopic hematuria is defined as ≥3 RBC/HPF on microscopic examination and has a 2.6-4% malignancy risk. 3, 1

Critical History and Physical Examination

Risk Stratification for Malignancy

Assess the following high-risk features that mandate complete urologic evaluation: 1

• Age: Males ≥60 years (high risk), 40-59 years (intermediate risk); Females ≥60 years (intermediate risk) 3
• Smoking history: >30 pack-years (high risk), 10-30 pack-years (intermediate risk) 3, 1
• Occupational exposure to benzenes, aromatic amines, or other chemicals/dyes 1, 4
• History of gross hematuria (even if currently microscopic) 1
• Irritative voiding symptoms (urgency, frequency, dysuria) without infection 1

Key Clinical Features

• Urine color: Tea-colored or cola-colored suggests glomerular disease; bright red suggests lower urinary tract bleeding 1
• Associated symptoms: Flank pain (nephrolithiasis, renal mass), dysuria (infection, malignancy), suprapubic pain 1
• Family history of kidney disease, hearing loss (Alport syndrome), or polycystic kidney disease 5
• Medication review: Anticoagulants/antiplatelets do NOT cause hematuria but may unmask underlying pathology—never defer evaluation based on these medications 1

Laboratory Evaluation

Urinalysis with Microscopy

Examine urinary sediment to distinguish glomerular from non-glomerular causes: 3, 1

• >80% dysmorphic RBCs or red blood cell casts indicate glomerular disease and require nephrology referral 3, 1
• >80% normal (eumorphic) RBCs suggest lower urinary tract bleeding 1
• Proteinuria: Spot urine protein-to-creatinine ratio >0.2 g/g suggests renal parenchymal disease 1

Additional Laboratory Tests

• Urine culture if infection suspected (obtain BEFORE antibiotics) 6, 1
• Serum creatinine, BUN, complete metabolic panel to assess renal function 6, 1
• Complete blood count with platelets to evaluate for coagulopathy 6
• Spot urine calcium-to-creatinine ratio to evaluate for hypercalciuria (associated with microscopic hematuria and nephrolithiasis) 3, 7

Imaging Strategy

For Non-Glomerular Hematuria

Multiphasic CT urography is the preferred imaging modality for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis in intermediate- and high-risk patients. 1 This includes unenhanced, nephrographic phase, and excretory phase images. 1

Alternative imaging if CT contraindicated: 1

• MR urography for patients with contrast allergy
• Renal ultrasound with retrograde pyelography for renal insufficiency

For Glomerular Hematuria

• Renal ultrasound to evaluate kidney size, echogenicity, and structural abnormalities (enlarged echogenic kidneys suggest acute glomerulonephritis; small kidneys suggest chronic kidney disease) 6, 1

Pediatric Considerations

• No imaging indicated for children with isolated microscopic hematuria without proteinuria or dysmorphic RBCs 6
• Renal ultrasound is the preferred modality in children to assess anatomy before potential renal biopsy 6

Cystoscopy

Cystoscopy is mandatory for: 1

• All patients with gross hematuria
• Microscopic hematuria patients with high-risk features (age >40 years, smoking history, occupational exposure, history of gross hematuria, irritative voiding symptoms)

Flexible cystoscopy is preferred over rigid cystoscopy as it causes less pain with equivalent or superior diagnostic accuracy. 1

Urine Cytology

Voided urine cytology should be obtained in high-risk patients (elderly, smoking history, occupational exposure) to detect high-grade urothelial carcinomas and carcinoma in situ. 1 However, do NOT obtain cytology in the initial evaluation of low-risk microscopic hematuria, as it is not recommended by current guidelines. 1

Nephrology Referral Indications

Immediate nephrology referral is indicated for: 1

• >80% dysmorphic RBCs or red blood cell casts (pathognomonic for glomerular disease) 3, 1
• Significant proteinuria (protein-to-creatinine ratio >0.2 g/g on three specimens) 1
• Elevated creatinine or declining renal function 1
• Hypertension with hematuria and proteinuria 1

Additional Glomerular Workup (if indicated)

• Complement levels (C3, C4) for post-infectious glomerulonephritis or lupus nephritis 1
• Antinuclear antibody (ANA) and ANCA if vasculitis suspected 1
• Audiogram and slit lamp examination if Alport syndrome suspected 6, 3
• Renal biopsy may be necessary for definitive diagnosis of IgA nephropathy, Alport syndrome, or other glomerular diseases 6

Follow-Up Protocol

For Negative Initial Evaluation with Persistent Hematuria

Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit. 3, 1

Immediate Re-evaluation Required If:

• Gross hematuria develops 1
• Significant increase in degree of microscopic hematuria 1
• New urologic symptoms (irritative voiding, flank pain) 1
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 1

Common Pitfalls to Avoid

• Never attribute hematuria to anticoagulation or antiplatelet therapy alone—these medications may unmask underlying pathology requiring investigation. 1
• Never ignore gross hematuria, even if self-limited—30-40% malignancy risk mandates urgent urologic referral. 1, 2
• Do not treat asymptomatic bacteriuria or pyuria with antibiotics—hematuria requires evaluation for urologic causes including malignancy, not antibiotic treatment. 1
• Do not delay cancer diagnosis by prescribing multiple courses of antibiotics for persistent hematuria—2 months of symptoms despite appropriate antibiotic therapy effectively rules out simple UTI. 1
• Do not perform extensive urologic workup for 0-2 RBCs/HPF—this falls within normal range and does not constitute true microscopic hematuria. 1

Age-Specific Algorithms

Adults (>40 years) with Microscopic Hematuria

1. Confirm ≥3 RBC/HPF on two of three specimens 1
2. Urinalysis with microscopy to assess for dysmorphic RBCs, casts, proteinuria 1
3. If glomerular features present → nephrology referral 1
4. If non-glomerular → CT urography + cystoscopy 1

Children with Isolated Microscopic Hematuria

1. Assess for proteinuria and dysmorphic RBCs 6
2. If absent → no imaging indicated, clinical follow-up 6
3. If present → renal ultrasound, consider nephrology referral 6
4. Screen family members for benign familial hematuria 6

Gross Hematuria (Any Age)

1. Urgent urologic referral 1, 2
2. CT urography (multiphasic) 1
3. Cystoscopy (mandatory) 1
4. Urine cytology 1