What are the next steps for a patient with red blood cells (RBCs) in their urine but no clear diagnosis of hematuria?

Microscopic Urinalysis Showing RBCs Without Documented Hematuria

You must first confirm true microscopic hematuria by repeating urinalysis to demonstrate ≥3 RBCs per high-power field on two of three properly collected clean-catch midstream specimens before initiating any workup, as dipstick results alone have limited specificity (65-99%) and cannot be relied upon. 1

Immediate Confirmation Steps

• Obtain microscopic examination of urinary sediment from properly collected specimens (clean-catch midstream) rather than relying on dipstick alone 1, 2
• Repeat urinalysis on 2-3 separate occasions to confirm persistent microscopic hematuria (defined as ≥3 RBCs/HPF) 1, 3
• Rule out benign transient causes before proceeding with extensive workup:
  • Menstruation in women (repeat 48 hours after cessation) 1, 2
  • Vigorous exercise (repeat 48 hours after cessation) 1, 3
  • Sexual activity or trauma (repeat 48 hours after cessation) 2
  • Viral illness 2
  • Urinary tract infection (obtain urine culture; if positive, treat and repeat urinalysis 6 weeks post-treatment) 1, 2

If Hematuria is Confirmed: Determine Glomerular vs Non-Glomerular Origin

This distinction is critical as it determines whether you pursue urologic or nephrologic evaluation.

Indicators of Glomerular Source (Nephrology Pathway):

• RBC casts (virtually pathognomonic for glomerular bleeding) 1
• Dysmorphic RBCs >80% on microscopic examination 1, 2, 3
• Significant proteinuria (>500-1000 mg/24 hours) 1, 2
• Elevated serum creatinine or reduced eGFR 1
• Tea-colored urine (suggests glomerular source) 3

Indicators of Non-Glomerular Source (Urology Pathway):

• Normal "doughnut-shaped" RBCs >80% 1, 3
• Absence of proteinuria, RBC casts, or renal dysfunction 1
• Risk factors for urologic malignancy (see below) 1, 2

Risk Stratification for Urologic Evaluation

High-risk patients require complete urologic evaluation even after single positive specimen:

• Age >35-40 years 1, 2, 3
• Smoking history (especially >10-30 pack-years) 1, 2, 3
• Occupational exposure to chemicals, dyes, benzenes, or aromatic amines 1, 2
• History of gross hematuria (even if self-limited) 1, 2, 3
• Irritative voiding symptoms 1, 2
• History of pelvic irradiation 1, 2
• Analgesic abuse 1, 2
• Male gender 3

Complete Urologic Evaluation (for Non-Glomerular Hematuria with Risk Factors)

• Cystoscopy should be performed on all patients ≥35 years old, or younger patients with risk factors 1, 3
• Multi-phasic CT urography is the imaging procedure of choice for upper tract evaluation 1, 3
• Assess renal function (eGFR, creatinine, BUN) 1
• Urine cytology in select cases 3

Nephrology Evaluation (for Glomerular Hematuria)

• Concurrent nephrology referral if dysmorphic RBCs, proteinuria, cellular casts, or renal insufficiency present 1, 2
• Quantify proteinuria with 24-hour urine collection (significant if >500-1000 mg/day) 1, 2
• Evaluate for systemic diseases associated with glomerulonephritis 1
• Consider renal biopsy when systemic causes not identified 1
• Monitor renal function, proteinuria, and blood pressure 1, 2

Critical Pitfalls to Avoid

• Never attribute hematuria solely to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology and full evaluation is still required 1, 2, 3
• Gross hematuria always requires urologic referral even if self-limited, as it carries 30-40% malignancy risk 3
• Do not skip microscopic confirmation—dipstick alone is insufficient due to false positives from myoglobin, hemoglobin, or other substances 1, 2, 3

Follow-Up for Negative Initial Evaluation

• Repeat urinalysis at 6,12,24, and 36 months if initial workup negative but hematuria persists 1, 2, 3
• Monitor blood pressure at each visit 1, 2
• Consider nephrology referral if hematuria persists with development of hypertension, proteinuria, or evidence of glomerular bleeding 2, 3