Causes of Hematuria
Classification and Major Etiologic Categories
Hematuria arises from urologic, renal/glomerular, or systemic causes, with the differential diagnosis ranging from benign conditions to life-threatening malignancies that demand urgent evaluation 1.
Urologic Causes (Non-Glomerular)
Malignancy represents the most critical urologic cause, accounting for 30-40% of gross hematuria cases and 2.6-4% of microscopic hematuria cases 1, 2. The three primary urologic malignancies include:
- Bladder cancer is the most frequently diagnosed malignancy in hematuria cases, presenting classically as painless gross hematuria in 70-80% of patients 1, 3
- Renal cell carcinoma causes upper tract bleeding and requires multiphasic CT urography for detection 1, 4
- Prostate cancer can produce lower urinary tract symptoms with hematuria 4
Benign urologic causes are common but never exclude concurrent malignancy:
- Benign prostatic hyperplasia (BPH) is the most common benign urologic cause specifically in men over 50 years, but gross hematuria from BPH must be proven through appropriate evaluation and does not exclude malignancy 2, 4
- Urinary tract infection causes both microscopic and macroscopic hematuria with pyuria and bacteriuria 1, 2, 5
- Urolithiasis (kidney and ureteric stones) typically causes painful hematuria with flank pain 1, 2, 6
- Trauma to kidneys or lower urinary tract produces hematuria requiring contrast-enhanced CT imaging 1
Renal/Glomerular Causes
Tea-colored urine accompanied by proteinuria, red blood cell casts, and >80% dysmorphic RBCs strongly suggests glomerular disease 1, 2. Key glomerular causes include:
- IgA nephropathy is the most common glomerular cause of hematuria worldwide 1, 2
- Post-infectious glomerulonephritis following streptococcal infection 1, 2
- Alport syndrome presents with hematuria, progressive kidney disease, hearing loss, and ocular abnormalities 1, 2
- Lupus nephritis and vasculitis cause hematuria with systemic manifestations 1
- Thin basement membrane nephropathy is an autosomal dominant condition causing progressive chronic kidney disease 1
Systemic and Other Causes
- Coagulopathies (hemophilia) cause hematuria due to bleeding disorders 1, 2
- Sickle cell disease causes hematuria through renal papillary necrosis 1, 2
- Vigorous exercise can cause transient hematuria that resolves with rest 1
- Menstruation can contaminate urine samples in women, leading to false-positive results 1
Critical Clinical Pitfall: Anticoagulation
Anticoagulant and antiplatelet medications may unmask underlying pathology but do not themselves cause hematuria—evaluation must proceed regardless of anticoagulation status 1, 2. This is a common error where clinicians defer workup, potentially missing malignancy 1.
Age-Specific Considerations
- In children: Glomerulonephritis and congenital anomalies are the most common causes 1, 2
- In adults >35-40 years: Malignancy risk increases significantly, with men >60 years having up to 21% prevalence of asymptomatic microscopic hematuria and higher risk for significant urologic disease 2, 4
Risk Factors for Malignancy
The following factors stratify patients into higher risk categories requiring aggressive evaluation 1, 2, 4:
- Male gender
- Age >35 years (particularly >60 years)
- Smoking history (>30 pack-years = high risk)
- Occupational exposure to benzenes, aromatic amines, or chemicals/dyes
- History of gross hematuria (30-40% malignancy risk regardless of other factors)
- Irritative voiding symptoms without infection
Distinguishing Glomerular from Non-Glomerular Sources
Examine urinary sediment for dysmorphic RBCs and red cell casts to determine the source 1, 2:
- Glomerular bleeding: >80% dysmorphic RBCs, red cell casts (pathognomonic), significant proteinuria (>500-1000 mg/24 hours), tea-colored urine 1, 2
- Lower urinary tract bleeding: >80% normal RBCs, absence of proteinuria or casts 1, 4
Essential Clinical Pearls
- Gross hematuria should never be ignored and requires urgent urologic referral even if self-limited, as it carries a 30-40% malignancy risk 1, 2, 4
- Dipstick positivity (65-99% specificity) must be confirmed with microscopic analysis showing ≥3 RBCs per high-power field on at least two of three properly collected specimens before initiating full workup 1, 2
- 0-2 RBCs/HPF falls within normal range and does not warrant urologic workup 1
- Red cell casts are virtually pathognomonic for glomerular bleeding 2