Causes of Hematuria
Classification by Source
Hematuria arises from either glomerular (renal parenchymal) or non-glomerular (urologic) sources, and distinguishing between these is the critical first step in determining etiology 1, 2.
Urologic (Non-Glomerular) Causes
Malignancy
- Bladder cancer is the most frequently diagnosed malignancy in hematuria cases, accounting for 30-40% of gross hematuria and 2.6-4% of microscopic hematuria 3.
- Renal cell carcinoma and transitional cell carcinoma of the upper urinary tract are also significant urologic malignancies 2.
- Risk factors include: male gender, age >35-40 years, smoking (especially >30 pack-years), and occupational exposure to benzenes or aromatic amines 4, 3.
Infection
- Urinary tract infection is a common cause of both microscopic and macroscopic hematuria, presenting with white blood cells and microorganisms in urine 3, 5.
- Urine cultures should be obtained before antibiotic therapy 1.
Urolithiasis
- Kidney and ureteric stones typically cause painful hematuria with flank pain 3.
- May be associated with hypercalciuria and hyperuricosuria 1.
Benign Prostatic Hyperplasia
Trauma
Glomerular (Renal Parenchymal) Causes
Primary Glomerular Diseases
- IgA nephropathy (Berger Disease) is a common cause of persistent isolated microscopic hematuria 1, 3.
- Post-infectious glomerulonephritis following streptococcal infection 3.
- Thin basement membrane nephropathy is an autosomal dominant condition causing asymptomatic hematuria, usually with a benign course 1.
- Alport syndrome is hereditary nephritis with associated hearing loss and ocular abnormalities 1, 3.
Key Diagnostic Features of Glomerular Bleeding
- >80% dysmorphic red blood cells in urinary sediment strongly suggests glomerular origin 1, 2.
- Red cell casts are virtually pathognomonic for glomerular bleeding 4.
- Tea-colored urine suggests a glomerular source 2, 3.
- Significant proteinuria (>1,000 mg/24 hours, or >500 mg/24 hours if persistent) indicates renal parenchymal disease 4, 1.
Systemic and Other Causes
Exercise-Related
Hematologic Disorders
- Coagulopathies (e.g., hemophilia) cause hematuria due to bleeding disorders 2, 3.
- Sickle cell disease causes hematuria through renal papillary necrosis 2, 3.
Medications
- Anticoagulants and antiplatelet agents may unmask underlying pathology but do not themselves cause hematuria 2, 3.
- These medications are not a reason to forgo evaluation of hematuria 2.
Metabolic Causes
- Hypercalciuria and hyperuricosuria can be associated with microscopic hematuria and may lead to nephrolithiasis 1, 2.
Other Benign Causes
- Menstruation can cause contamination of urine samples in women, leading to false-positive results 2.
- Nutcracker syndrome (left renal vein compression) causes hematuria with variable proteinuria 2.
Age-Specific Considerations
Pediatric Patients
Elderly Patients
- Malignancy risk increases significantly with age, particularly over 35-40 years 3.
- In older men (>60 years), the prevalence of asymptomatic microscopic hematuria can be as high as 21%, with higher risk for significant urologic disease 4.
Critical Clinical Pearls
Gross vs. Microscopic Hematuria
- Gross hematuria carries a 30-40% risk of malignancy and should never be ignored, requiring urgent urologic referral even if self-limited 2, 3.
- Microscopic hematuria most commonly has benign causes, with malignancy risk of only 2.6-4% 1, 5.
Common Pitfalls
- Dipstick positivity 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 2, 3.
- In approximately 80% of cases of asymptomatic microscopic hematuria, no cause is ever found (idiopathic) 1.
- Anticoagulation is not an explanation for hematuria and should not defer evaluation 4, 2.