How should intermittent hematuria in a man taking bupropion be evaluated and managed?

Evaluation and Management of Intermittent Male Hematuria

Immediate Diagnostic Confirmation

Confirm true microscopic hematuria with a properly collected clean-catch midstream urine specimen showing ≥3 red blood cells per high-power field (RBC/HPF) on microscopic examination before initiating any workup. 1, 2 Dipstick testing alone has only 65-99% specificity and can yield false positives from myoglobin, hemoglobin, or contaminants. 1, 2

Bupropion Is Not the Cause

Bupropion does not cause hematuria and should not be discontinued or blamed for urinary bleeding. 2 The documented adverse effects of bupropion include seizures (approximately 1 per 1,000 users), dry mouth, constipation, headache, dizziness, insomnia, and nausea—hematuria is not among these. 2 You may safely continue bupropion while proceeding with urgent urologic evaluation. 2

Risk Stratification Determines Evaluation Intensity

High-Risk Features Requiring Full Urologic Workup (Cystoscopy + CT Urography):

• Age ≥40 years (you meet this criterion as a male patient) 1, 2
• Smoking history >30 pack-years 1, 2
• Any history of gross (visible) hematuria, even if intermittent or self-limited 1, 2
• Occupational exposure to benzenes, aromatic amines, or other chemicals/dyes 1
• Irritative voiding symptoms (urgency, frequency, dysuria) without documented infection 1
• Microscopic hematuria >25 RBC/HPF 2

If you have ANY of these features, proceed immediately to complete urologic evaluation regardless of the intermittent nature of bleeding. 1, 2

Complete Urologic Evaluation Protocol

Upper Tract Imaging:

Multiphasic CT urography (unenhanced, nephrographic, and excretory phases) is the preferred imaging modality, with 96% sensitivity and 99% specificity for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis. 1, 2 This single study evaluates kidneys, collecting systems, ureters, and bladder comprehensively. 1, 2

Lower Tract Evaluation:

Flexible cystoscopy is mandatory for all males ≥40 years with confirmed microscopic hematuria to directly visualize bladder mucosa, urethra, and ureteral orifices. 1, 2 Flexible cystoscopy provides equivalent or superior diagnostic accuracy to rigid cystoscopy with significantly less discomfort. 1, 2

Adjunctive Testing:

Voided urine cytology should be obtained if you have high-risk features (age >60 years, smoking >30 pack-years, or occupational chemical exposures) to detect high-grade urothelial carcinomas and carcinoma in situ. 1, 2

Exclude Glomerular Disease

Before proceeding with urologic workup, assess for glomerular sources:

• Examine urinary sediment for dysmorphic RBCs (>80% suggests glomerular origin) and red cell casts (pathognomonic for glomerulonephritis) 2, 3
• Measure spot urine protein-to-creatinine ratio; values >0.5 g/g indicate renal parenchymal disease requiring nephrology referral 2, 3
• Check serum creatinine and BUN to evaluate renal function 1, 2
• Tea-colored or cola-colored urine suggests glomerular bleeding 2

If glomerular features are present, refer to nephrology in addition to completing urologic evaluation—malignancy can coexist with medical renal disease. 2, 3

Critical Pitfalls to Avoid

• Never dismiss intermittent hematuria as benign—cancer-related hematuria is often intermittent, which is why current AUA guidelines recommend proceeding with evaluation based on a single positive microscopic result when hematuria is significant. 1, 2
• Never attribute hematuria to anticoagulation or antiplatelet therapy; these medications may unmask underlying pathology but do not cause hematuria themselves. 1, 2, 4
• Never delay evaluation in males ≥40 years—age alone is sufficient justification for complete urologic workup. 1, 2
• Gross hematuria carries a 30-40% malignancy risk and mandates urgent urologic referral even if self-limited. 1, 2

Follow-Up Protocol If Initial Workup Is Negative

• Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit 2, 3
• After two consecutive negative annual urinalyses, further testing is unnecessary 2, 3
• Immediate re-evaluation is warranted if: gross hematuria develops, significant increase in microscopic hematuria occurs, new urologic symptoms appear, or hypertension/proteinuria/glomerular bleeding emerges 2, 3
• Consider repeat complete evaluation within 3-5 years for persistent hematuria in high-risk patients 2

Specific Algorithm for Your Case

1. Obtain microscopic urinalysis today to confirm ≥3 RBC/HPF 1, 2
2. Check spot urine protein-to-creatinine ratio and serum creatinine 2, 3
3. If ≥3 RBC/HPF confirmed and you are ≥40 years old: Schedule multiphasic CT urography and flexible cystoscopy regardless of bupropion use 1, 2
4. If glomerular features present (dysmorphic RBCs >80%, red cell casts, protein-to-creatinine ratio >0.5 g/g): Add nephrology referral 2, 3
5. Continue bupropion throughout evaluation unless your prescribing physician advises otherwise for unrelated reasons 2