What is the appropriate workup for an adult patient with no known medical history presenting with dark urine?

Dark Urine Workup in Adults

For an adult with no known medical history presenting with dark urine, immediately confirm true hematuria with microscopic urinalysis showing ≥3 RBCs per high-power field, then proceed with complete urologic evaluation including cystoscopy and CT urography, while simultaneously ruling out benign causes and assessing for glomerular disease. 1, 2

Initial Assessment and Confirmation

Distinguish True Hematuria from Other Causes of Dark Urine

• Obtain microscopic urinalysis immediately to confirm ≥3 red blood cells per high-power field—dipstick positivity alone (65-99% specificity) is insufficient and should never trigger imaging without microscopic confirmation 1, 2
• Differentiate hematuria from hemoglobinuria and myoglobinuria by examining for intact RBCs on microscopy; dipstick-positive urine without RBCs suggests hemoglobinuria (intravascular hemolysis) or myoglobinuria (rhabdomyolysis) 3, 4
• Consider non-blood causes of dark urine including medications (rifampin, nitrofurantoin, metronidazole), foods (beets, blackberries), metabolic disorders (porphyria, alkaptonuria), and bile pigments 5, 6, 7

Rule Out Benign Transient Causes

• Obtain detailed history focusing on recent vigorous exercise, menstruation timing in women, recent urologic procedures, and current medications including anticoagulants 1, 2
• Perform urine culture if infection suspected (dysuria, frequency, urgency), preferably before antibiotics, though infection does not exclude concurrent malignancy 1, 2
• Repeat urinalysis after treating benign causes (infection, menstruation) to confirm persistence—if hematuria resolves, no further workup needed 1, 2

Risk Stratification for Malignancy

High-Risk Features Requiring Immediate Complete Evaluation

• Gross (visible) hematuria carries 30-40% malignancy risk and mandates urgent urologic referral with cystoscopy and CT urography, even if self-limited 1, 2
• Age >35-40 years (men ≥40 years intermediate risk, ≥60 years high risk; women ≥60 years intermediate risk) 1, 2, 8
• Smoking history >30 pack-years represents high risk for urothelial carcinoma 2, 8
• Occupational exposure to benzenes, aromatic amines, or other chemicals/dyes (painters, hairdressers, rubber/textile workers) 1, 2
• History of prior gross hematuria, even if remote 2
• Irritative voiding symptoms (urgency, frequency, nocturia) without documented infection 1, 2

Complete Urologic Evaluation

Upper Tract Imaging

• Multiphasic CT urography is the preferred imaging modality with unenhanced, nephrographic, and excretory phases to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1, 2, 8
• Alternative imaging if CT contraindicated: MR urography for patients with renal insufficiency (eGFR <30) or contrast allergy; renal ultrasound combined with retrograde pyelography is less optimal but acceptable 1, 2
• Assess renal function with serum creatinine and eGFR before contrast studies to guide imaging selection and evaluate for intrinsic renal disease 1, 8

Lower Tract Evaluation

• Cystoscopy is mandatory for all adults ≥35 years with confirmed microscopic hematuria and for all patients with gross hematuria regardless of age 1, 2
• Flexible cystoscopy is preferred over rigid due to less pain, fewer post-procedure symptoms, and equivalent or superior diagnostic accuracy 1, 2, 8
• Voided urine cytology should be obtained in high-risk patients to detect high-grade urothelial carcinomas and carcinoma in situ, though not recommended for routine initial evaluation in low-risk patients 1, 2

Concurrent Nephrologic Assessment

Indicators of Glomerular Disease

• Examine urinary sediment for dysmorphic RBCs (>80% dysmorphic suggests glomerular origin) and red blood cell casts (pathognomonic for glomerular disease) 1, 2, 8
• Tea-colored or cola-colored urine strongly suggests glomerular bleeding rather than urologic causes 1, 2
• Check for proteinuria using spot urine protein-to-creatinine ratio (normal <0.2 g/g); significant proteinuria with hematuria indicates likely glomerular disease 2, 8
• Assess blood pressure as hypertension with hematuria and proteinuria suggests glomerulonephritis 1, 2

When to Refer to Nephrology

• Immediate nephrology referral indicated for: persistent significant proteinuria (protein-to-creatinine ratio >0.2), presence of red cell casts or >80% dysmorphic RBCs, elevated creatinine or declining renal function, or hypertension with hematuria and proteinuria 2, 8
• Additional glomerular workup may include: complement levels (C3, C4) for post-infectious glomerulonephritis or lupus, ANA and ANCA if vasculitis suspected, and renal ultrasound to assess kidney size and echogenicity 2

Critical Pitfalls to Avoid

• Never attribute hematuria solely to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria themselves; proceed with full evaluation regardless 1, 2
• Do not prescribe antibiotics for persistent hematuria without documented infection—this delays cancer diagnosis and provides false reassurance 2
• Never ignore gross hematuria even if self-limited—30-40% malignancy risk mandates urgent evaluation 1, 2
• Do not rely on dipstick alone—confirm with microscopic examination showing ≥3 RBCs/HPF on at least two of three properly collected specimens 1, 2
• Benign prostatic hyperplasia in men does not exclude concurrent malignancy—complete evaluation still required 2

Follow-Up Protocol if Initial Workup Negative

• Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit 1, 8
• Immediate re-evaluation warranted if: recurrent gross hematuria, significant increase in microscopic hematuria, new urologic symptoms, or development of hypertension/proteinuria 1, 2, 8
• Consider repeat anatomic evaluation within 3-5 years for persistent microscopic hematuria, particularly in high-risk patients 1
• Release from care after two consecutive negative annual urinalyses (one per year for two years from initial evaluation) in patients with initially negative workup 1