What is the differential diagnosis for cola-colored urine?

Differential Diagnosis of Cola-Colored Urine

Cola-colored urine most commonly indicates glomerulonephritis (particularly post-infectious or IgA nephropathy), myoglobinuria from rhabdomyolysis, or gross hematuria from urinary tract pathology—and requires immediate urinalysis with microscopy to differentiate these life-threatening conditions. 1

Primary Diagnostic Categories

Glomerular Disease (Most Common Cause of True "Cola" Color)

• Post-infectious glomerulonephritis presents with tea/cola-colored urine, proteinuria (>2+ on dipstick), RBC casts, and dysmorphic RBCs on phase contrast microscopy 1
• IgA nephropathy (Berger disease) is a common glomerular cause requiring renal biopsy for definitive diagnosis 1
• Diabetic kidney disease accounts for 30-40% of chronic kidney disease cases and can present with proteinuria causing dark urine 1
• The presence of >80% dysmorphic RBCs on microscopy strongly suggests glomerulonephritis 1

Myoglobinuria (Critical to Identify Early)

• Rhabdomyolysis causes myoglobin release with elevated total creatine kinase and requires aggressive IV hydration to prevent acute kidney injury 1
• Cocaine use can trigger rhabdomyolysis with elevated myoglobin and creatine kinase 1
• Dipstick will be positive for "blood" but microscopy shows no RBCs (myoglobin cross-reacts with hemoglobin detection) 2, 3

Hematuria-Related Causes

• Urinary tract infection with gross hematuria 1
• Urolithiasis causing bleeding 1
• Trauma to the urinary tract 1
• Dipstick positive for blood with microscopic RBCs present indicates true hematuria 1

Medication-Induced Discoloration

• Metronidazole can cause cola-colored urine without clinical harm—this is a benign side effect that resolves when the medication is stopped 4
• The discoloration recurs upon medication rechallenge and requires no intervention beyond patient reassurance 4
• Highly colored urine from various medications can cause false-positive ketone results 5

Hemolysis-Related

• Post-artemisinin delayed hemolysis occurs 7-21 days after artesunate treatment for malaria, presenting with "Coca-Cola"-colored urine, severe hemolytic anemia, hemoglobinuria, hyperbilirubinemia, and raised lactate dehydrogenase 6
• This condition is usually self-limiting but can cause life-threatening anemia requiring blood transfusion 6

Acute Porphyria (Rare but Important)

• Acute intermittent porphyria can present with red-brown urine that darkens upon standing or exposure to light, with PBG/creatinine ratio increased >10 times upper limit of normal during acute attacks 5
• Urine may appear normal initially but develops typical red-brown color after exposure to light or heat 5

Essential Initial Workup

Immediate Laboratory Testing

• Complete urinalysis with microscopy to detect RBCs, WBCs, casts, and assess for dysmorphic RBCs 1
• Urine albumin-to-creatinine ratio (UACR) or protein-to-creatinine ratio for quantification (abnormal if >30 mg/g) 1
• Serum creatinine and eGFR to assess kidney function 1
• Complete blood count to evaluate for anemia, thrombocytosis, or leukocytosis 1
• Creatine kinase if myoglobinuria suspected 1

Additional Testing Based on Initial Results

• Inflammatory markers (CRP) if systemic disease suspected 1
• Urine specific gravity and pH help narrow differential diagnosis 3
• Renal ultrasound to assess kidney size, echogenicity, morphology, and detect hydronephrosis or obstruction 1

Critical Red Flags Requiring Urgent Action

Immediate Nephrology Referral Indicated For:

• Persistent proteinuria >1,000 mg/24 hours 1
• Red cell casts or dysmorphic RBCs >80% 1
• eGFR <30 mL/min/1.73 m² requires immediate nephrology consultation 1
• Rapidly declining eGFR or continuously increasing albuminuria despite treatment 1

Emergency Department Evaluation Required For:

• Fever, tachycardia, or signs of systemic illness with cola-colored urine 1
• Urinary retention or obstruction with hydronephrosis 1
• Suspected rhabdomyolysis requiring aggressive IV hydration and creatine kinase monitoring 1

Diagnostic Algorithm

1. Obtain urinalysis with microscopy immediately to differentiate between hematuria (RBCs present), myoglobinuria (dipstick positive for blood but no RBCs), and pigmenturia 1, 2

2. If RBCs present on microscopy: Assess for dysmorphic RBCs and casts to distinguish glomerular (>80% dysmorphic RBCs, RBC casts) from non-glomerular causes 1

3. If dipstick positive for blood but no RBCs: Check creatine kinase for rhabdomyolysis and consider hemoglobinuria from hemolysis 1, 6

4. If proteinuria >2+ with RBC casts: Presume glomerulonephritis and refer urgently to nephrology for possible renal biopsy 1

5. Review medication list: Consider metronidazole or other drugs as benign causes if workup otherwise negative 4

Common Pitfalls to Avoid

• Do not dismiss cola-colored urine as benign without proper urinalysis—glomerulonephritis and rhabdomyolysis require urgent intervention 1
• Do not rely on dipstick alone—microscopy is essential to differentiate true hematuria from myoglobinuria or hemoglobinuria 1, 2
• Do not overlook medication history—metronidazole causes harmless discoloration that mimics serious pathology 4
• Do not delay nephrology referral when red cell casts or significant proteinuria are present—early intervention improves outcomes 1
• Remember post-artemisinin delayed hemolysis occurs 7-21 days after treatment, requiring safety netting advice and hemoglobin monitoring 6