What tests should be ordered for a patient with chronic hematuria (blood in urine)?

Diagnostic Workup for Chronic Hematuria

For chronic hematuria, order urinalysis with microscopy to confirm ≥3 RBCs/HPF, followed by urine culture, serum creatinine, and assessment for proteinuria and dysmorphic RBCs to distinguish glomerular from non-glomerular causes—then proceed with CT urography and cystoscopy for non-glomerular hematuria, or nephrology referral for glomerular disease. 1, 2

Initial Laboratory Confirmation

Confirm true hematuria first:

• Microscopic urinalysis showing ≥3 red blood cells per high-power field on at least two of three properly collected clean-catch midstream specimens 1, 2
• Dipstick alone has only 65-99% specificity and produces false positives—never proceed with extensive workup based on dipstick alone 1
• Exclude benign transient causes: menstruation, vigorous exercise, sexual activity, recent trauma, viral illness 2

Core Laboratory Tests

Order these tests for all confirmed chronic hematuria:

• Complete urinalysis with sediment examination to assess RBC morphology, presence of casts, white blood cells, bacteria, and degree of proteinuria 1, 2
• Serum creatinine, BUN, and complete metabolic panel to evaluate renal function 1, 3
• Urine culture to rule out infection 3, 2
• Spot urine protein-to-creatinine ratio (normal <0.2 g/g) to quantify proteinuria 1

Critical Decision Point: Glomerular vs Non-Glomerular Source

Examine urinary sediment carefully to determine the source:

Glomerular Source Indicators (Nephrology Referral):

• >80% dysmorphic red blood cells 1
• Red blood cell casts (pathognomonic for glomerular disease) 1, 3
• Significant proteinuria (protein-to-creatinine ratio >0.2) 1
• Elevated serum creatinine or declining renal function 1
• Tea-colored urine suggests glomerular bleeding 1

Non-Glomerular Source Indicators (Urologic Evaluation):

• >80% normal-shaped RBCs 1
• Minimal or no proteinuria 3
• Normal serum creatinine 3

Additional Tests for Glomerular Disease

If glomerular source suspected, add:

• Complement levels (C3, C4) to evaluate for post-infectious glomerulonephritis or lupus nephritis 1
• Antinuclear antibody (ANA) and ANCA testing if vasculitis suspected 1
• Renal ultrasound to evaluate kidney size and echogenicity (enlarged echogenic kidneys suggest acute glomerulonephritis; small atrophic kidneys suggest chronic disease) 4, 1

Complete Urologic Evaluation for Non-Glomerular Hematuria

For non-glomerular hematuria, order:

Upper Tract Imaging:

• CT urography (multiphasic CT with contrast) is the preferred imaging modality to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1, 3, 2
• MR urography as alternative if CT contraindicated 3
• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation 1

Lower Tract Evaluation:

• Cystoscopy is mandatory for all patients ≥40 years and those <40 with risk factors (smoking, occupational chemical/dye exposure, irritative voiding symptoms, history of gross hematuria) 1, 2
• Flexible cystoscopy causes less pain with equivalent diagnostic accuracy 1

Urine Cytology:

• Voided urine cytology for high-risk patients: age >40 years, smoking history >10 pack-years, occupational exposures, pelvic irradiation, irritative voiding symptoms, analgesic abuse 1, 2
• Particularly sensitive for high-grade tumors and carcinoma in situ 1

Risk Stratification for Malignancy

Assess these risk factors to determine urgency:

• Age: Women ≥60 years and men ≥40 years are higher risk 1
• Smoking history: >30 pack-years is high risk 1
• Occupational exposure to benzenes, aromatic amines, chemicals, or dyes 1, 3
• Gross hematuria carries 30-40% malignancy risk vs 2.6-4% for microscopic 1, 3

Metabolic Evaluation for Persistent Microscopic Hematuria

If initial workup negative, consider:

• Urine calcium-to-creatinine ratio to evaluate for hypercalciuria (associated with microscopic hematuria and nephrolithiasis) 4, 1
• Uric acid levels to assess for hyperuricosuria 4
• Renal ultrasound with Doppler if nutcracker syndrome (left renal vein compression) suspected 1

Follow-Up Protocol for Negative Initial Evaluation

If complete workup is negative but hematuria persists:

• Repeat urinalysis at 6,12,24, and 36 months 1, 2
• Monitor blood pressure at each visit 1, 2
• Immediate re-evaluation if gross hematuria develops, significant increase in microscopic hematuria, new urologic symptoms, or development of hypertension/proteinuria 1

Critical Pitfalls to Avoid

Do not make these common errors:

• Never attribute hematuria to anticoagulation or antiplatelet therapy alone—these medications may unmask underlying pathology but do not cause hematuria 1, 3
• Never defer evaluation in patients on warfarin, aspirin, or other blood thinners—full workup is still mandatory 1, 3
• Never ignore gross hematuria even if self-limited—it requires urgent urologic referral due to 30-40% malignancy risk 1, 3
• Never rely on dipstick alone—always confirm with microscopic examination 1, 2
• Never skip cystoscopy in patients ≥40 years with confirmed hematuria—bladder cancer can be missed without direct visualization 2

Specialist Referral Indications

Nephrology referral indicated for:

• Persistent significant proteinuria (protein-to-creatinine ratio >0.2 on three specimens) 1
• Red cell casts or >80% dysmorphic RBCs 1
• Elevated creatinine or declining renal function 1
• Hypertension with hematuria and proteinuria 1

Urologic referral indicated for:

• All gross hematuria cases 3, 2
• Microscopic hematuria in patients ≥40 years 2
• Any patient with risk factors for malignancy 3, 2
• Irritative voiding symptoms without infection 1