What is the approach to a patient presenting with painless hematuria, particularly in terms of diagnostic workup and management?

Approach to Painless Hematuria

Adults with gross hematuria require urgent urologic referral for cystoscopy and imaging regardless of whether it is self-limited, as the cancer risk consistently exceeds 10% and can reach 25% in referral populations. 1

Initial Confirmation and Risk Stratification

Confirm True Hematuria

• Verify microscopic hematuria by documenting ≥3 red blood cells per high-power field on microscopic examination of at least two of three properly collected clean-catch midstream urine specimens, as dipstick testing alone has only 65-99% specificity 2
• Exclude spurious causes including menstrual contamination, recent strenuous exercise, foods (beets, rhubarb), and medications 1

Distinguish Glomerular from Non-Glomerular Sources

• Examine urinary sediment for dysmorphic red blood cells (>80% dysmorphic RBCs strongly suggests glomerular bleeding) and red blood cell casts (pathognomonic for glomerular disease) 2
• Check for proteinuria using spot urine protein-to-creatinine ratio (normal <0.2 g/g), as the combination of proteinuria with hematuria significantly increases likelihood of glomerular disease 2

Diagnostic Workup Based on Clinical Presentation

For Gross (Visible) Hematuria in Adults

Immediate urologic referral is mandatory for comprehensive evaluation including cystoscopy and upper tract imaging, as approximately 20% of patients harbor a urological tumor. 3, 1, 4

• Perform thorough cystoscopic examination evaluating tumor size, location, configuration, number, and mucosal abnormalities 3
• Obtain contrast-enhanced CT urography (CT abdomen/pelvis with contrast) as the gold standard imaging modality 3, 5
• Alternative imaging includes MRI urography when CT is contraindicated; retrograde pyelogram or intravenous urography may be used when CT/MRI unavailable 3

For Microscopic Hematuria in Adults Without Proteinuria or Dysmorphic RBCs

• Refer for urologic evaluation with cystoscopy and imaging in the absence of a demonstrable benign cause 1
• Upper urinary tract imaging should be performed as a component of initial evaluation 3
• If normal cystoscopy but positive cytology, consider prostatic urethral biopsies, upper tract imaging, enhanced cystoscopic techniques (blue light cystoscopy when available), ureteroscopy, or random bladder biopsies 3

For Hematuria with Proteinuria or Dysmorphic RBCs (Suspected Glomerular Disease)

Immediate nephrology referral is indicated rather than urologic workup, as these findings suggest intrinsic renal disease. 2

• Obtain complete metabolic panel, complement levels (C3, C4), antinuclear antibody (ANA), ANCA testing, and complete blood count with platelets 2
• Perform renal ultrasound to assess kidney size and echogenicity (enlarged echogenic kidneys suggest acute glomerulonephritis; atrophic kidneys with altered corticomedullary differentiation indicate chronic disease) 2
• CT urography and cystoscopy are NOT indicated when glomerular disease is suspected 2

Special Populations and Scenarios

Children with Painless Hematuria

• Children with isolated microscopic hematuria lacking proteinuria or dysmorphic red blood cells require no imaging or further workup, as studies of 325 pediatric patients found no clinically significant findings on renal ultrasound or voiding cystourethrography 1, 3
• For isolated macroscopic hematuria in children, renal and bladder ultrasound is the initial imaging modality to exclude nephrolithiasis, urologic abnormalities, and rarely tumors 1
• Evaluate for recent streptococcal infection, family history of renal disease or hearing loss, sickle cell disease, bleeding disorders, and medications 1

Hematuria with Palpable Abdominal Mass

• Urgent ultrasound evaluation is required to confirm renal origin of the mass and assess for inferior vena cava involvement, tumor size, and extent 1

Common Pitfalls to Avoid

• Do not rely on dipstick alone—always confirm with microscopic examination, as false positives occur with myoglobinuria, hemoglobinuria, and certain medications 2
• Do not delay urologic referral for gross hematuria even if it resolves spontaneously—the cancer risk remains elevated 1
• Do not order CT urography for suspected glomerular disease—this wastes resources and exposes patients to unnecessary radiation when nephrology referral is appropriate 2
• Do not assume urinary tract infection explains hematuria without confirming resolution—repeat urinalysis 6 weeks post-treatment; if hematuria persists, proceed with full urologic evaluation 5

Follow-Up for Negative Initial Workup

• Even with negative cystoscopy and imaging, guidelines recommend semi-annual follow-up for 3 years in primary care, as some malignancies may be missed on initial evaluation 6