What is the appropriate workup for a patient presenting with hematuria, considering age, medical history, and potential risk factors for malignancy?

Workup of 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 positivity alone has limited specificity (65-99%) and produces false positives from myoglobin, hemoglobin, menstrual contamination, or vigorous exercise 2, 1
• For high-risk patients (age >40 years, smoking history, occupational chemical exposure, history of gross hematuria), a single specimen with ≥3 RBC/HPF may warrant immediate full evaluation 1, 3
• In women, obtain catheterized specimen if vaginal contamination suspected; in uncircumcised men, retract foreskin or catheterize if phimosis present 2

Exclude Transient Benign Causes

If history suggests potential benign causes (menstruation, vigorous exercise, sexual activity, recent trauma), repeat urinalysis 48 hours after cessation of the activity—no further evaluation needed if hematuria resolves. 2

• Urinary tract infection requires treatment with urine culture obtained before antibiotics, then repeat urinalysis six weeks post-treatment 2, 1
• Critical pitfall: Anticoagulation or antiplatelet therapy does NOT cause hematuria—these medications may unmask underlying pathology and evaluation must proceed regardless 1, 3

Distinguish Glomerular from Non-Glomerular Sources

Examine urinary sediment for dysmorphic RBCs (>80% indicates glomerular disease), red cell casts (pathognomonic for glomerular disease), and significant proteinuria (protein-to-creatinine ratio >0.2 g/g). 2, 1

Features Suggesting Glomerular Disease (Nephrology Referral):

• Dysmorphic RBCs >80% or red cell casts present 1
• Significant proteinuria (>500-1000 mg/24h or spot protein-to-creatinine ratio >0.2) 1
• Elevated serum creatinine or declining renal function 1
• Tea-colored or cola-colored urine 1
• Hypertension accompanying hematuria 1

Glomerular Workup (if features present):

• Complete metabolic panel including serum creatinine, BUN, albumin 1
• Complement levels (C3, C4) for post-infectious glomerulonephritis or lupus nephritis 1
• ANA and ANCA testing if vasculitis suspected 1
• Renal ultrasound to assess kidney size and echogenicity 1
• Immediate nephrology referral indicated 1

Risk Stratification for Urologic Malignancy

Gross hematuria carries 30-40% malignancy risk and requires urgent urologic referral with complete evaluation regardless of whether self-limited or if benign cause suspected. 1, 4

High-Risk Features (Require Full Urologic Evaluation):

• Age: Males ≥60 years, females ≥60 years 1, 3
• Smoking: >30 pack-years 1, 3
• History of gross hematuria (even if currently microscopic) 1, 3
• Occupational exposure to chemicals/dyes (benzenes, aromatic amines) 1, 3
• Irritative voiding symptoms without infection (urgency, frequency, dysuria) 1, 3
• History of urologic disorders or pelvic irradiation 1

Intermediate-Risk Features:

• Males 40-59 years 1
• Females <60 years with other risk factors 1
• Smoking 10-30 pack-years 1

Low-Risk Features:

• Males <40 years without other risk factors 1
• Never smoker or <10 pack-years 1
• 3-10 RBC/HPF without other risk factors 1

Complete Urologic Evaluation (for Non-Glomerular Hematuria)

Laboratory Testing:

• Serum creatinine to assess renal function 2, 1
• Complete urinalysis with microscopy 1
• Urine culture if infection suspected (before antibiotics) 1
• Voided urine cytology for high-risk patients (age >60, smoking history, irritative symptoms, occupational exposure) 2, 1

Upper Tract Imaging:

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, 3

• CT urography includes unenhanced, nephrographic, and excretory phases for comprehensive evaluation 1
• If CT contraindicated (renal insufficiency, contrast allergy): MR urography or renal ultrasound with retrograde pyelography 1
• Traditional intravenous urography (IVU) remains acceptable but has limited sensitivity for small renal masses 2, 1
• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation in adults 1

Lower Tract Evaluation:

Cystoscopy is mandatory for all patients with gross hematuria and for microscopic hematuria patients with intermediate or high-risk features. 1, 3

• Flexible cystoscopy preferred over rigid (less pain, equivalent or superior diagnostic accuracy) 1, 4
• Evaluates bladder mucosa, urethra, ureteral orifices for transitional cell carcinoma 1
• Urothelial cancers are the most commonly detected malignancies in patients with hematuria 2

Age-Specific Modifications

Young Males (<40 years) with Gross Hematuria:

• Start with renal and bladder ultrasound (low radiation, high yield for stones, congenital anomalies) 4
• Cystoscopy not routinely indicated unless ultrasound abnormal, persistent hematuria, or risk factors present 4
• Obtain family history of kidney disease, hearing loss, polycystic kidney disease 4

Children:

• Ultrasound preferred imaging modality 1
• No imaging indicated for isolated microscopic hematuria without proteinuria or dysmorphic RBCs 1
• Consider glomerulonephritis and congenital anomalies as common causes 1

Elderly (≥60 years):

• Automatically high-risk—require full evaluation with CT urography and cystoscopy 1, 3
• Urine cytology strongly recommended due to high transitional cell carcinoma risk 1

Follow-Up Protocol for Negative Initial Evaluation

If complete workup negative but hematuria persists, repeat urinalysis, voided urine cytology, and blood pressure measurement at 6,12,24, and 36 months. 1, 4

Immediate Re-Evaluation Warranted If:

• Gross hematuria develops 1, 4
• Significant increase in degree of microscopic hematuria 1
• New urologic symptoms appear (irritative voiding, flank pain) 1, 4
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 1

Critical pitfall: Hematuria can precede bladder cancer diagnosis by many years—long-term surveillance essential in high-risk patients. 1

Common Pitfalls to Avoid

• Never ignore gross hematuria even if self-limited—30-40% malignancy risk mandates urgent evaluation 1
• Never attribute hematuria to anticoagulation/antiplatelet therapy alone—these unmask underlying pathology requiring investigation 1
• Never rely on dipstick alone—always confirm with microscopic examination showing ≥3 RBC/HPF 1
• Never treat asymptomatic bacteriuria with pyuria and hematuria—hematuria requires urologic evaluation, not antibiotics 1
• Never defer evaluation in patients on anticoagulation—proceed with full workup 1
• Benign prostatic hyperplasia can cause hematuria but does not exclude concurrent malignancy 1