What are the causes of brown urine and the appropriate work‑up?

Brown Urine: Causes and Diagnostic Approach

Brown urine requires immediate differentiation between true hematuria (blood in urine), hemoglobinuria (free hemoglobin), myoglobinuria (muscle breakdown), and non-blood pigments—each demands a distinct diagnostic pathway and carries different implications for morbidity and mortality. 1

Immediate Diagnostic Steps

• Obtain microscopic urinalysis on a properly collected clean-catch specimen to determine if red blood cells are actually present (≥3 RBC/HPF confirms true hematuria). 1
• Perform urine dipstick testing to check for blood, protein, and other markers—but recognize that dipstick positivity for blood occurs with hematuria, hemoglobinuria, AND myoglobinuria, so microscopy is essential to differentiate. 1, 2
• Examine the color characteristics: tea-colored or cola-colored urine suggests glomerular bleeding, while red-brown urine without RBCs on microscopy indicates hemoglobinuria or myoglobinuria. 1, 2

Three Critical Entities to Distinguish

1. True Hematuria (RBCs Present on Microscopy)

Glomerular Source Indicators:

• Tea-colored or cola-colored urine 1
• Dysmorphic RBCs >80% on urinary sediment 1
• Red blood cell casts (pathognomonic for glomerular disease) 1
• Significant proteinuria (protein-to-creatinine ratio >0.5 g/g) 1
• Elevated serum creatinine 1

Non-Glomerular (Urologic) Source Indicators:

• Normal-shaped RBCs with minimal proteinuria 1
• Age >35–40 years, smoking history, or occupational chemical exposure 1
• Flank pain, dysuria, or irritative voiding symptoms 1

Management for True Hematuria:

• If glomerular indicators present: immediate nephrology referral plus measure serum creatinine, BUN, complement levels (C3, C4), ANA, and ANCA if vasculitis suspected. 1
• If urologic indicators present in adults ≥40 years: urgent urology referral for multiphasic CT urography and flexible cystoscopy (gross hematuria carries 30–40% malignancy risk). 1

2. Hemoglobinuria (Dipstick Positive, NO RBCs on Microscopy)

Key Features:

• Urine dipstick positive for blood but microscopy shows zero or minimal intact RBCs 2
• Red-brown or dark brown urine color 2
• Caused by intravascular hemolysis releasing free hemoglobin into plasma that exceeds haptoglobin binding capacity 2

Common Causes:

• Paroxysmal nocturnal hemoglobinuria (PNH)—presents with episodic dark urine, often worse in morning 2
• Transfusion reactions 2
• Autoimmune hemolytic anemia 2
• G6PD deficiency with oxidative stress 2
• Mechanical hemolysis (prosthetic heart valves, march hemoglobinuria) 2

Diagnostic Workup:

• Complete blood count with reticulocyte count, peripheral smear, LDH, haptoglobin, indirect bilirubin 2
• Direct antiglobulin test (Coombs) 2
• Flow cytometry for CD55/CD59 if PNH suspected 2
• Do NOT pursue extensive urologic workup—this is a hematologic emergency, not a urologic problem. 2

3. Myoglobinuria (Dipstick Positive, NO RBCs, Risk of Acute Kidney Injury)

Key Features:

• Urine dipstick positive for blood but microscopy shows no RBCs 3
• Red-brown or tea-colored urine 3
• Caused by rhabdomyolysis (muscle breakdown) releasing myoglobin 3

High-Risk Clinical Scenarios:

• Trauma, crush injuries, prolonged immobilization 3
• Severe exertion, heat stroke, seizures 3
• Drug toxicity (statins, cocaine, amphetamines) 3
• Compartment syndrome 3

Diagnostic Workup:

• Serum creatine kinase (CK) is the key test—levels >1,000 U/L (often 10–150× normal) confirm rhabdomyolysis 3
• Serum creatinine and BUN to assess for acute kidney injury 3
• Serum potassium, phosphate, calcium (watch for hyperkalemia and hypocalcemia) 3
• Urine myoglobin can be measured but CK is more practical 3

Management:

• Aggressive IV fluid resuscitation to prevent acute tubular necrosis and renal failure 3
• Monitor urine output, electrolytes, and renal function closely 3
• This is a medical emergency—four of the most severely affected patients in one study developed acute renal failure. 3

Non-Blood Causes of Brown Urine

Medications and Foods:

• Metronidazole, nitrofurantoin, methyldopa, levodopa 4, 5
• Fava beans, rhubarb, aloe 4, 5
• Senna laxatives 4, 5

Metabolic Conditions:

• Porphyria (urine darkens on standing, turns port-wine color) 5
• Alkaptonuria (urine darkens on standing due to homogentisic acid) 5
• Melanuria (rare, associated with metastatic melanoma) 5

Diagnostic Clues:

• Urine pH and specific gravity help narrow differential 5
• Ferric chloride test can detect phenolic compounds in porphyria 5
• UV light examination may reveal fluorescence in certain conditions 5

Critical Pitfalls to Avoid

• Never assume brown urine is "just" from dehydration or vitamins—always confirm with microscopic urinalysis to rule out life-threatening causes. 1, 2
• Never attribute brown urine to anticoagulation without full evaluation—anticoagulants unmask underlying pathology but do not cause hematuria. 1
• Never delay evaluation of myoglobinuria—acute renal failure can develop rapidly and requires immediate aggressive hydration. 3
• Never perform extensive urologic workup for hemoglobinuria—this wastes time and resources when the patient needs hematologic evaluation. 2
• Dipstick alone is insufficient—it cannot distinguish hematuria from hemoglobinuria or myoglobinuria; microscopy is mandatory. 1, 2

Practical Diagnostic Algorithm

1. Brown urine reported → Order microscopic urinalysis + urine dipstick + serum CK + CBC
2. Dipstick positive for blood + RBCs ≥3/HPF → True hematuria → Assess for glomerular vs. urologic source
3. Dipstick positive for blood + NO RBCs + CK >1,000 U/L → Myoglobinuria → Aggressive IV hydration + monitor renal function
4. Dipstick positive for blood + NO RBCs + normal CK → Hemoglobinuria → Hematology workup for hemolysis
5. Dipstick negative for blood → Consider medications, foods, porphyria, alkaptonuria