What are the evaluation and treatment steps for hematuria (blood in urine)?

Evaluation and Management of Hematuria (Blood in Urine)

All patients with gross (visible) hematuria require urgent urologic referral for cystoscopy and imaging, even if the bleeding resolves spontaneously, due to malignancy risk exceeding 10%. 1, 2

Initial Confirmation and Classification

Confirm dipstick-positive results with microscopic urinalysis showing ≥3 red blood cells per high-power field before initiating any workup. 3, 1 Dipstick testing has limited specificity (65-99%) and can yield false positives from myoglobin, hemoglobin, or menstrual contamination. 3

Distinguish Between Gross and Microscopic Hematuria:

• Gross hematuria (visible blood): 30-40% malignancy risk—requires immediate urologic evaluation 3, 2
• Microscopic hematuria (≥3 RBCs/HPF): 2.6-4% malignancy risk—evaluation based on risk stratification 3

Critical pitfall: Painless gross hematuria has stronger cancer association than hematuria with flank pain, which may suggest stone disease. 2 However, never dismiss gross hematuria regardless of associated symptoms. 1

Risk Stratification for Microscopic Hematuria

High-Risk Features Requiring Full Urologic Evaluation:

• Age: Men ≥40 years, women ≥60 years 3
• Smoking history >10 pack-years 3
• Occupational exposure to chemicals/dyes (benzenes, aromatic amines) 3
• History of gross hematuria 3
• History of urologic disorders 3

Important caveat: Anticoagulation or antiplatelet therapy does NOT explain hematuria and should never defer evaluation—these medications may unmask underlying pathology. 3, 1, 2

Determine Source: Glomerular vs. Non-Glomerular

Glomerular Source Indicators:

• 80% dysmorphic red blood cells 3

• Red cell casts (pathognomonic for glomerular disease) 3
• Significant proteinuria (spot protein-to-creatinine ratio >0.2 g/g) 3
• Tea-colored urine 3
• Elevated serum creatinine 3

Non-Glomerular (Urologic) Source Indicators:

• 80% normal-shaped RBCs 3

• Minimal or no proteinuria 2
• Normal serum creatinine 2

Complete Urologic Evaluation (for Non-Glomerular Source)

Imaging:

CT urography (multiphasic) is the preferred imaging modality for comprehensive upper tract evaluation to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis. 3, 2 MR urography is an alternative if CT is contraindicated. 2

Cystoscopy:

Mandatory for all patients with gross hematuria and high-risk microscopic hematuria to evaluate for bladder transitional cell carcinoma, the most frequently diagnosed malignancy in hematuria cases. 3, 2

Laboratory Testing:

• Urine culture (preferably before antibiotics if infection suspected) 3
• Serum creatinine and complete metabolic panel 3
• Urine cytology for high-risk patients (age ≥80 years, heavy smoking history, occupational exposures) 3, 2

Important note: Do NOT obtain urinary cytology or urine-based molecular markers for initial bladder cancer screening in low-risk patients. 1

Nephrology Evaluation (for Glomerular Source)

Indications for Nephrology Referral:

• Persistent significant proteinuria (protein-to-creatinine ratio >0.2 on three specimens) 3
• Red cell casts or >80% dysmorphic RBCs 3
• Elevated creatinine or declining renal function 3
• Hypertension with hematuria and proteinuria 3

Additional Testing for Suspected Glomerular Disease:

• Complement levels (C3, C4) for post-infectious glomerulonephritis or lupus nephritis 3
• Antinuclear antibody (ANA) and ANCA if vasculitis suspected 3
• Renal ultrasound to assess kidney size and echogenicity 3
• Consider renal biopsy through nephrology 3

Management of Specific Scenarios

If Urinary Tract Infection Identified:

Treat infection and repeat urinalysis after treatment completion. 3 If hematuria persists after infection clearance, proceed with full evaluation. 3

If Initial Workup Negative:

Repeat urinalysis, voided urine cytology, and blood pressure measurement at 6,12,24, and 36 months. 3, 2 Consider nephrology referral if hematuria persists with development of hypertension, proteinuria, or evidence of glomerular bleeding. 3

Immediate Urologic Reevaluation Required If:

• Recurrent gross hematuria 2
• Abnormal urinary cytology 2
• Irritative voiding symptoms without infection 2

Common Pitfalls to Avoid

• Never ignore gross hematuria, even if self-limited—30-40% malignancy risk mandates evaluation. 3, 1
• Never attribute hematuria solely to anticoagulation—these medications unmask pathology rather than cause it. 3, 4
• Never delay urologic referral in elderly patients with gross hematuria while waiting for other test results. 2
• Never assume microscopic hematuria is benign without confirmation—requires two of three specimens showing ≥3 RBCs/HPF. 3
• Never use "benign familial hematuria" terminology—this prompts loss to follow-up when annual monitoring is needed. 5