What is the appropriate workup for a patient presenting with microscopic hematuria?

Workup for Microscopic Hematuria

Confirm true microscopic hematuria with ≥3 red blood cells per high-power field on microscopic examination of at least two of three properly collected clean-catch midstream urine specimens before initiating any workup, as dipstick tests have limited specificity (65-99%) and should never trigger imaging or investigation alone. 1, 2

Initial Confirmation and Exclusion of Benign Causes

• Verify microscopic hematuria by obtaining at least two of three properly collected urine specimens showing ≥3 RBCs/HPF on microscopic examination, not just dipstick positivity 1, 2
• Exclude transient benign causes including menstruation, vigorous exercise within 48 hours, recent sexual activity, viral illness, and trauma 2, 3
• If urinary tract infection is suspected, obtain urine culture before antibiotics, treat appropriately, and repeat urinalysis 6 weeks after completing treatment to confirm resolution of hematuria 3
• Persistence of hematuria after treating UTI mandates full urologic evaluation, as approximately 3% of patients with microscopic hematuria harbor genitourinary malignancy 3

Determine Glomerular vs. Non-Glomerular Source

Examine urinary sediment with microscopy to assess for dysmorphic RBCs, red blood cell casts, and degree of proteinuria to distinguish glomerular from non-glomerular bleeding 2, 3:

• Glomerular indicators include >80% dysmorphic RBCs, red cell casts (pathognomonic for glomerular disease), significant proteinuria (>500 mg/24 hours), elevated serum creatinine, or tea-colored/cola-colored urine 1, 2, 3
• Non-glomerular bleeding is characterized by >80% normal-appearing RBCs and bright red urine 1

If Glomerular Source Suspected

• Measure serum creatinine, BUN, complete metabolic panel to assess renal function 1
• Check complement levels (C3, C4) to evaluate for post-infectious glomerulonephritis or lupus nephritis 1
• Obtain ANA and ANCA testing if vasculitis is suspected 1
• Refer to nephrology for persistent proteinuria (protein-to-creatinine ratio >0.2), presence of red cell casts, >80% dysmorphic RBCs, elevated creatinine, or hypertension with hematuria 1, 2

Risk Stratification for Urologic Malignancy

Stratify patients into risk categories based on the American Urological Association criteria to determine the intensity of urologic evaluation 1:

High-Risk Features (Require Cystoscopy + CT Urography)

• Age ≥60 years in men or women 1, 3
• Smoking history >30 pack-years 1, 3

• 25 RBCs/HPF on single urinalysis 3

• History of gross hematuria 1, 3
• Occupational exposure to chemicals/dyes (benzenes, aromatic amines) 1, 3
• Irritative voiding symptoms without infection 1, 3
• History of pelvic irradiation 3
• Analgesic abuse 3

Intermediate-Risk Features (Shared Decision-Making for Cystoscopy + Imaging)

• Women age 50-59 years or men age 40-59 years 1, 3
• Smoking history 10-30 pack-years 1
• 11-25 RBCs/HPF on single urinalysis 3

Low-Risk Features (May Defer Cystoscopy, Consider Repeat UA in 6 Months)

• Women <50 years or men <40 years 3
• Never smoker or <10 pack-years 1, 3
• 3-10 RBCs/HPF on single urinalysis 1
• No additional risk factors 3

Complete Urologic Evaluation for Non-Glomerular Hematuria

Upper Tract Imaging

Multiphasic CT urography is the preferred imaging modality for comprehensive evaluation of the upper urinary tract, including unenhanced, nephrographic, and excretory phases to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1, 2, 4:

• CT urography has 92% sensitivity and 93% specificity for detecting urologic pathology 5
• If CT is contraindicated (renal insufficiency, contrast allergy), use MR urography or renal ultrasound with retrograde pyelography as alternatives, though less optimal 1
• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation due to limited sensitivity for small renal masses 1

Lower Tract Evaluation

Cystoscopy is mandatory for all patients ≥40 years of age and for patients <40 years with risk factors (smoking, occupational exposures, irritative voiding symptoms, history of gross hematuria) 2, 3:

• Flexible cystoscopy is preferred over rigid cystoscopy as it causes less pain, has fewer post-procedure symptoms, and demonstrates equivalent or superior diagnostic accuracy 1, 2
• Cystoscopy visualizes bladder mucosa, urethra, and ureteral orifices to detect transitional cell carcinoma, which is the most frequently diagnosed malignancy in hematuria cases 1

Additional Testing

• Urine cytology is recommended in all patients with risk factors for transitional cell carcinoma, particularly to detect high-grade tumors and carcinoma in situ 2, 3
• Serum creatinine measurement is necessary to assess renal function 2, 3

Follow-Up Protocol for Negative Initial Evaluation

If the complete workup is negative but hematuria persists, implement structured surveillance 2, 3:

• Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit 1, 2, 3
• Consider repeat cystoscopy and imaging within 3-5 years for persistent or recurrent hematuria, particularly in high-risk populations 3
• Immediate re-evaluation is warranted if gross hematuria develops, significant increase in microscopic hematuria occurs, new urologic symptoms appear, or development of hypertension/proteinuria 1, 2, 3

Critical Pitfalls to Avoid

• Never attribute hematuria to anticoagulation or antiplatelet therapy alone—these medications may unmask underlying pathology but do not cause hematuria, and evaluation should proceed regardless 1, 2
• Never ignore gross hematuria, even if self-limited—it carries a 30-40% malignancy risk and mandates urgent urologic referral 1, 2
• Never rely on dipstick alone—always confirm with microscopic examination showing ≥3 RBCs/HPF before initiating workup 1, 2
• Never treat asymptomatic bacteriuria or pyuria with antibiotics—hematuria requires evaluation for urologic causes, not empiric antibiotic treatment 1
• In children with isolated microscopic hematuria without proteinuria or dysmorphic RBCs, no imaging is indicated as they are unlikely to have clinically significant renal disease 6