What is the appropriate workup for a patient presenting with dark urine?

Workup for Dark Urine

The first priority is to distinguish true hematuria from other causes of dark urine through urinalysis with microscopy, then proceed with risk-stratified evaluation based on whether hematuria is confirmed and the patient's clinical presentation. 1

Initial Diagnostic Steps

Confirm the Cause of Dark Urine

• Obtain urinalysis with microscopy immediately to differentiate between hematuria (≥3 RBCs/HPF), hemoglobinuria (positive dipstick but no RBCs on microscopy), myoglobinuria, or pigmenturia from medications/foods 1, 2
• Dipstick testing alone has only 65-99% specificity and requires microscopic confirmation before proceeding with extensive workup 1, 3
• Tea-colored or cola-colored urine suggests glomerular disease, while bright red urine indicates lower urinary tract bleeding [1, @29@]
• If dipstick is positive for blood but microscopy shows <3 RBCs/HPF, consider hemoglobinuria (from intravascular hemolysis) or myoglobinuria (from rhabdomyolysis) 2

Essential Laboratory Evaluation

• Complete urinalysis with microscopy examining for dysmorphic RBCs (>80% suggests glomerular source), red cell casts (pathognomonic for glomerular disease), proteinuria, and other cellular elements [1, @14@]
• Urine culture (preferably before antibiotics) to exclude urinary tract infection, even if infection seems unlikely 1, 3
• Serum creatinine, BUN, and complete metabolic panel to assess renal function and identify medical renal disease 1, 3
• Spot urine protein-to-creatinine ratio if proteinuria is present on dipstick (normal <0.2 g/g) [@12@]

Risk Stratification for Hematuria

High-Risk Features Requiring Urgent Complete Urologic Evaluation

• Any gross hematuria (30-40% malignancy risk) - requires urgent evaluation even if self-limited [1, @30@]
• Age ≥60 years in men or women [1, @18@]
• Smoking history >30 pack-years [1, @18@]
• Occupational exposure to chemicals, dyes, benzenes, or aromatic amines [1, @18@]
• Irritative voiding symptoms without infection (urgency, frequency, dysuria) 1, 3
• History of gross hematuria even if currently microscopic [@18@]

• 25 RBCs/HPF on microscopy [@33@]

Complete Urologic Evaluation for High-Risk Patients

• Multiphasic CT urography (unenhanced, nephrographic, and excretory phases) is the imaging modality of choice for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis [1,3, @24@]
• Cystoscopy is mandatory for all patients with gross hematuria and high-risk microscopic hematuria to visualize bladder mucosa, urethra, and ureteral orifices [4,1, @30@]
• Flexible cystoscopy is preferred over rigid cystoscopy due to less pain and equivalent diagnostic accuracy [1, @30@]
• Voided urine cytology in high-risk patients to detect high-grade urothelial carcinomas and carcinoma in situ [4, @30@]

Glomerular vs. Non-Glomerular Differentiation

Features Suggesting Glomerular Source

• >80% dysmorphic RBCs on phase-contrast microscopy [1, @14@]
• Red blood cell casts (pathognomonic for glomerular disease) [@12@, @14@]
• Significant proteinuria (protein-to-creatinine ratio >0.2 g/g) accompanying hematuria [1, @12@]
• Tea-colored or cola-colored urine [1, @29@]
• Hypertension with hematuria [@12@, @30@]

Additional Workup for Suspected Glomerular Disease

• Complement levels (C3, C4) to evaluate for post-infectious glomerulonephritis or lupus nephritis [@12@]
• Antinuclear antibody (ANA) and ANCA testing if vasculitis suspected [@12@]
• Nephrology referral indicated for persistent significant proteinuria, red cell casts, >80% dysmorphic RBCs, elevated creatinine, or hypertension with hematuria and proteinuria [1, @12@]
• Renal ultrasound to evaluate kidney size and echogenicity (enlarged echogenic kidneys suggest acute glomerulonephritis) [@12@]

Alternative Causes of Dark Urine

Non-Hematuria Causes to Consider

• Hemoglobinuria: Positive dipstick but no RBCs on microscopy; consider paroxysmal nocturnal hemoglobinuria, hemolytic anemia, or transfusion reactions 2
• Myoglobinuria: Positive dipstick but no RBCs; consider rhabdomyolysis from trauma, seizures, or strenuous exercise 2, 5
• Medications: Rifampin (orange-red), nitrofurantoin (brown), metronidazole (dark brown), phenazopyridine (orange) 5, 6
• Foods: Beets, blackberries, rhubarb can cause red/pink urine 5, 6
• Metabolic disorders: Porphyria (port-wine colored), alkaptonuria (darkens on standing), homogentisic acid oxidase deficiency 5, 6, 7

Critical Pitfalls to Avoid

• Never dismiss hematuria in patients on anticoagulation or antiplatelet therapy - these medications unmask underlying pathology but do not cause hematuria themselves 1, 3, 8
• Never accept self-limited gross hematuria as benign - 30-40% harbor malignancy and require complete evaluation [1, @30@]
• Never attribute hematuria to benign prostatic hyperplasia without complete evaluation - malignancy can coexist [4, @23@]
• Never delay evaluation for presumed urinary tract infection - treat infection but recognize malignancy can coexist [4, @31@]
• Anticoagulation is not a reason to forgo evaluation of hematuria 1

Follow-Up Protocol for Negative Initial Evaluation

• Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit [1, @33@]
• Immediate re-evaluation warranted if gross hematuria develops, significant increase in microscopic hematuria occurs, new urologic symptoms appear, or development of hypertension/proteinuria [1, @30@]
• After two consecutive negative annual urinalyses, no further testing for asymptomatic microhematuria is necessary [@33@]
• Consider repeat complete evaluation within 3-5 years for persistent hematuria in high-risk patients [@33@]