What are the possible causes of pink urine and how should it be evaluated?

Pink Urine: Causes and Evaluation

Immediate Diagnostic Confirmation

Pink urine most commonly indicates hematuria (blood in the urine), but you must confirm true hematuria with microscopic urinalysis showing ≥3 red blood cells per high-power field (RBC/HPF) before initiating any workup. 1 Dipstick testing alone has only 65–99% specificity and can produce false positives from myoglobin, hemoglobin, menstrual contamination, or certain foods and medications. 1

Distinguish True Hematuria from Pseudohematuria

• If the dipstick is positive for blood but microscopy shows no red blood cells, consider hemoglobinuria (from intravascular hemolysis) or myoglobinuria (from rhabdomyolysis). 2
• If the dipstick is negative but urine appears pink, suspect pigmenturia from foods (beets, blackberries), medications (rifampin, phenazopyridine, certain laxatives), or porphyria. 3, 4
• In women, obtain a catheterized specimen if menstrual contamination is suspected from a clean-catch sample. 1

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Causes of True Hematuria (Confirmed ≥3 RBC/HPF)

Urologic (Non-Glomerular) Causes

• Malignancy accounts for 30–40% of gross hematuria cases and 2.6–4% of microscopic hematuria, with bladder cancer being the most common. 1, 5 Risk factors include age >35 years, smoking >30 pack-years, male gender, and occupational exposure to benzenes or aromatic amines. 1, 5
• Urinary tract infection presents with dysuria, urgency, frequency, and white blood cells/bacteria on urinalysis. 1, 5
• Urolithiasis (kidney or ureteral stones) typically causes painful hematuria with flank pain. 1, 5
• Benign prostatic hyperplasia in older men can cause hematuria but does not exclude concurrent malignancy. 1
• Trauma to the kidneys or lower urinary tract, even minor trauma to an anomalous kidney, can produce significant bleeding. 1, 6

Renal/Glomerular Causes

• Glomerulonephritis (post-infectious, IgA nephropathy, lupus nephritis, vasculitis) presents with tea-colored or cola-colored urine, proteinuria >0.5 g/g, >80% dysmorphic RBCs, or red blood cell casts. 1, 5
• Alport syndrome (hereditary nephritis with hearing loss and ocular abnormalities) should be suspected with family history of kidney disease. 1, 5
• Thin basement membrane nephropathy is the most common cause of benign familial hematuria. 1, 6

Systemic/Other Causes

• Vigorous exercise can cause transient, self-limited hematuria that resolves with rest. 1, 6
• Coagulopathies (hemophilia, platelet disorders) or anticoagulant/antiplatelet therapy may unmask underlying pathology but do not cause hematuria themselves—evaluation must proceed regardless. 1, 5
• Sickle cell disease causes hematuria through renal papillary necrosis. 1, 6
• Hypercalciuria and hyperuricosuria are metabolic causes that may lead to microscopic hematuria and nephrolithiasis. 1, 6

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Risk Stratification and Evaluation Algorithm

High-Risk Features (Require Urgent Urologic Evaluation)

• Age ≥60 years (men or women) 1
• Smoking history >30 pack-years 1
• Any episode of gross (visible) hematuria, even if self-limited 1
• Occupational exposure to benzenes, aromatic amines, or industrial chemicals 1
• Irritative voiding symptoms (urgency, frequency, dysuria) without documented infection 1
• Microscopic hematuria >25 RBC/HPF 5

If any high-risk feature is present, proceed immediately to:

1. Multiphasic CT urography (unenhanced, nephrographic, and excretory phases) to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis with 96% sensitivity and 99% specificity. 1, 5
2. Flexible cystoscopy to directly visualize the bladder mucosa, urethra, and ureteral orifices—mandatory because imaging alone cannot exclude bladder cancer. 1, 5
3. Voided urine cytology in high-risk patients to detect high-grade urothelial carcinomas. 1

Intermediate-Risk Features (Shared Decision-Making)

• Age 40–59 years (men) or age ≥60 years with lower-risk features (women) 1
• Smoking history 10–30 pack-years 1

Low-Risk Features (May Defer Extensive Imaging)

• Age <40 years (men) or <60 years (women) 1
• Never smoker or <10 pack-years 1
• 3–10 RBC/HPF 1

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Distinguishing Glomerular from Urologic Sources

Glomerular Indicators (Require Nephrology Referral)

• Tea-colored or cola-colored urine 1, 5
• Proteinuria >0.5 g/g on spot urine protein-to-creatinine ratio 1
• >80% dysmorphic RBCs on phase-contrast microscopy 1, 5
• Red blood cell casts (pathognomonic for glomerular disease) 1, 5
• Elevated serum creatinine or declining eGFR 1
• Hypertension accompanying hematuria and proteinuria 1

If glomerular features are present, refer to nephrology in addition to completing urologic evaluation, as malignancy can coexist with medical renal disease. 1

Urologic Indicators

• Normal-shaped RBCs (>80%) with minimal or no proteinuria 1
• Bright red or pink urine (suggests lower urinary tract bleeding) 1
• Flank pain, suprapubic pain, or dysuria 1

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Special Populations

Pediatric Patients

• Isolated microscopic hematuria without proteinuria or dysmorphic RBCs does not require imaging in otherwise well children. 6
• Gross hematuria requires renal and bladder ultrasound to exclude nephrolithiasis, anatomic abnormalities, and rarely tumors. 6
• Traumatic hematuria with high-energy mechanism, hypotension, or ≥50 RBC/HPF requires contrast-enhanced CT. 6
• Common pediatric causes include urinary tract infection, post-infectious glomerulonephritis, IgA nephropathy, and hypercalciuria. 6

Patients on Anticoagulation

• Never attribute hematuria to anticoagulant or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria. 1, 5 Full evaluation must proceed.

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Follow-Up for Negative Initial Evaluation

• Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit. 1
• After two consecutive negative annual urinalyses, further testing is unnecessary. 1
• Immediate re-evaluation is warranted if:
  • Gross hematuria develops 1
  • Significant increase in microscopic hematuria 1
  • New urologic symptoms appear 1
  • Hypertension, proteinuria, or glomerular bleeding develops 1

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Critical Pitfalls to Avoid

• Never ignore gross hematuria, even if self-limited—it carries a 30–40% malignancy risk and mandates urgent urologic referral. 1, 5
• Do not rely solely on dipstick testing—confirm with microscopic urinalysis showing ≥3 RBC/HPF. 1
• Do not defer evaluation due to anticoagulation—these medications do not cause hematuria. 1, 5
• Do not assume infection explains hematuria in patients >35 years—age alone is a sufficient risk factor for full workup. 1
• Do not delay cystoscopy while pursuing additional imaging—bladder cancer cannot be excluded by imaging alone. 1