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

Hematuria Workup

Initial Confirmation and Classification

All patients with suspected hematuria require microscopic urinalysis confirmation showing ≥3 red blood cells per high-power field before initiating any workup, as dipstick testing alone has limited specificity (65-99%). 1, 2

• Gross (macroscopic) hematuria carries a 30-40% malignancy risk and demands urgent urologic evaluation regardless of other factors 2, 3, 4
• Microscopic hematuria has a 2.6-4% malignancy risk and requires risk stratification before determining evaluation intensity 2, 4
• Confirm microscopic hematuria on at least two of three properly collected clean-catch midstream specimens before proceeding 1, 2

Exclude Benign Transient Causes

Before extensive workup, rule out temporary causes that resolve within 48 hours of cessation: 1

• Vigorous exercise 1, 2
• Menstruation (obtain catheterized specimen if contamination suspected) 1, 2
• Recent sexual activity 1
• Urinary tract infection (treat and repeat urinalysis 6 weeks post-treatment; if hematuria resolves, no further evaluation needed) 1

Critical pitfall: Never attribute hematuria to anticoagulation or antiplatelet therapy alone—these medications unmask underlying pathology but do not cause hematuria and should never defer evaluation. 1, 2, 3

Determine Glomerular vs. Non-Glomerular Source

This distinction fundamentally changes the workup pathway: 1, 2

Glomerular Origin (Nephrology Referral)

• >80% dysmorphic RBCs on phase-contrast microscopy 1, 2
• Red blood cell casts (pathognomonic for glomerular disease) 1, 2
• Significant proteinuria (protein-to-creatinine ratio >0.2-0.3 g/g) 1, 2
• Elevated serum creatinine or declining renal function 2
• Tea-colored urine 2, 4

Non-Glomerular Origin (Urologic Evaluation)

• >80% normal (isomorphic) RBCs 2, 4
• Minimal or no proteinuria 4
• Normal serum creatinine 4

Risk Stratification for Malignancy (Non-Glomerular Hematuria)

The American Urological Association stratifies patients into risk categories that determine evaluation intensity: 2, 4

High Risk (Requires Full Urologic Evaluation)

• Men ≥60 years OR women ≥60 years 2, 4
• Smoking history >30 pack-years 2, 4
• ≥25 RBCs per high-power field 2, 4
• History of gross hematuria 2
• Occupational exposure to benzenes, aromatic amines, or other bladder carcinogens 1, 2, 3
• History of pelvic irradiation 3
• Chronic indwelling catheter use 3

Intermediate Risk

• Men 40-59 years OR women ≥60 years 2, 4
• Smoking history 10-30 pack-years 2, 4
• 11-25 RBCs per high-power field 2, 4

Low Risk

• Men <40 years AND women <60 years 2, 4
• Never smoker or <10 pack-years 2, 4
• 3-10 RBCs per high-power field 2, 4

Complete Laboratory Evaluation

All Patients with Confirmed Hematuria

• Comprehensive urinalysis with microscopic examination (quantify RBCs, assess for dysmorphic RBCs, casts, proteinuria) 1, 2
• Serum creatinine and BUN 1, 2
• Urine culture if infection suspected (obtain before antibiotics) 1, 3

If Glomerular Source Suspected

• Complete metabolic panel including albumin and total protein 2
• Spot urine protein-to-creatinine ratio 2
• Complement levels (C3, C4) for post-infectious glomerulonephritis or lupus nephritis 2
• Antinuclear antibody (ANA) and ANCA if vasculitis suspected 2
• Complete blood count with platelets 1, 2
• Consider audiogram and slit lamp examination if Alport syndrome suspected 1

High-Risk Patients (Non-Glomerular)

• Voided urine cytology (particularly useful for detecting carcinoma in situ, though not recommended for routine low-risk microscopic hematuria) 1, 3

Important caveat: Urine cytology should not be used as a screening tool in low-risk asymptomatic microscopic hematuria, but is valuable in high-risk patients and as an adjunct to cystoscopy. 1, 4

Imaging Strategy

Gross Hematuria (All Patients)

Multiphasic CT urography is the preferred imaging modality and should be performed urgently, even if bleeding is self-limited. 1, 3, 5

• CT urography detects renal cell carcinoma, transitional cell carcinoma, and urolithiasis with superior sensitivity compared to other modalities 1, 5
• Do not delay imaging for self-limited episodes—30-40% harbor malignancy 3, 4

Microscopic Hematuria (Risk-Stratified Approach)

High-risk patients: CT urography 1, 2

Intermediate-risk patients: CT urography or renal ultrasound with bladder imaging 1, 2

Low-risk patients without proteinuria or dysmorphic RBCs: No imaging initially indicated 1, 2

Pregnant patients: Ultrasound is first-line; defer full workup until after delivery unless gross hematuria or concerning features present (malignancy rate is very low in pregnancy) 1

Glomerular Hematuria

• Renal ultrasound to assess kidney size, echogenicity, and structural abnormalities 2
• Enlarged echogenic kidneys suggest acute glomerulonephritis 2
• Small kidneys indicate chronic kidney disease 1

Common pitfall: CT is not appropriate for isolated microscopic hematuria in children without proteinuria or concerning features. 1, 4

Cystoscopic Evaluation

Cystoscopy is mandatory for all patients with gross hematuria and high-risk microscopic hematuria to exclude bladder malignancy (the most commonly detected malignancy in hematuria cases). 1, 3

• Perform urgently in gross hematuria, even if bleeding resolves 3
• Required if urine cytology shows malignant or atypical cells 1
• May be deferred in low-risk microscopic hematuria patients 2

Nephrology Referral Indications

Refer to nephrology when glomerular disease is suspected or confirmed: 1, 2

• Persistent significant proteinuria (protein-to-creatinine ratio >0.2 on three specimens) 2
• Red cell casts or >80% dysmorphic RBCs 2
• Elevated creatinine or declining renal function 2
• Hypertension with hematuria and proteinuria 2
• Persistent microscopic hematuria with development of proteinuria or hypertension during follow-up 1, 2

Renal biopsy is usually recommended if systemic causes are not identified and glomerular disease is suspected. 1

Follow-Up Protocol for Negative Initial Evaluation

If complete urologic evaluation is negative in non-glomerular microscopic hematuria: 1, 2

• Repeat urinalysis at 6,12,24, and 36 months 1, 2
• Monitor blood pressure at each visit 1, 2
• Voided urine cytology at follow-up visits (optional) 1
• Consider nephrology referral if hematuria persists with development of hypertension, proteinuria, or evidence of glomerular bleeding 1, 2

Patients with isolated hematuria and negative workup have low risk for progressive renal disease but require surveillance due to limited long-term follow-up data. 1

Special Population Considerations

Pediatric Patients

• Isolated microscopic hematuria without proteinuria rarely requires imaging 1, 4
• Ultrasound is first-line for macroscopic hematuria to exclude tumors, stones, and anatomic abnormalities 4
• CT with IV contrast indicated for traumatic hematuria with concerning mechanism, even if only microscopic 4
• Screen family members for benign familial hematuria and thin basement membrane nephropathy 1

Elderly Males with Gross Hematuria

• Highest malignancy risk group requiring urgent complete evaluation 2, 3
• Do not attribute to benign prostatic hyperplasia without full workup—malignancy can coexist 3
• Smoking cessation counseling should be provided at initial visit 3