Causes of Gross Hematuria
Gross hematuria has a broad differential diagnosis spanning urologic malignancies (30–40% of cases), benign urologic conditions, glomerular disease, systemic disorders, and occasionally non-hematuria mimics—all of which require systematic evaluation to exclude life-threatening pathology. 1
Urologic Malignancies (Most Critical to Exclude)
- Bladder cancer is the most frequently diagnosed malignancy in patients presenting with hematuria, accounting for 30–40% of gross hematuria cases. 1, 2
- Renal cell carcinoma can present with painless gross hematuria and is detected on multiphasic CT urography. 3
- Upper tract urothelial carcinoma (renal pelvis, ureter) is less common but must be excluded with dedicated imaging. 1
- Prostate cancer may produce lower urinary tract symptoms and hematuria, particularly in older men with elevated PSA. 3
Clinical Pearl: Even self-limited gross hematuria carries a 30–40% malignancy risk and mandates urgent urologic referral with cystoscopy and upper tract imaging—never dismiss it as benign without complete evaluation. 4, 1
Benign Urologic Causes
- Benign prostatic hyperplasia (BPH) is the most common benign urologic cause of hematuria in men over 50, but does not exclude concurrent malignancy and requires proven prostatic origin through cystoscopy. 3, 2
- Urinary tract infection (UTI) causes hematuria with pyuria, bacteriuria, dysuria, urgency, and fever; however, infection does not exclude malignancy and hematuria must be re-evaluated after treatment if it persists. 1, 2
- Urolithiasis (kidney or ureteral stones) typically presents with painful hematuria, flank pain, and is readily detected on CT urography. 1, 3, 2
- Trauma to the kidneys or lower urinary tract from blunt or penetrating injury, instrumentation, or vigorous exercise can cause transient hematuria. 1, 3
Pitfall: Pyuria or positive urine culture does not exclude malignancy—if hematuria persists 6 weeks after treating infection, proceed immediately with full urologic evaluation. 1
Glomerular/Renal Parenchymal Causes
- IgA nephropathy is the most common primary glomerulonephritis worldwide and presents with episodic gross hematuria, often following upper respiratory infection. 2
- Post-infectious glomerulonephritis (typically post-streptococcal) causes tea- or cola-colored urine, hypertension, edema, and low complement levels. 1, 2
- Alport syndrome is a hereditary nephritis with progressive kidney disease, sensorineural hearing loss, and ocular abnormalities (lenticonus). 1, 2
- Thin basement membrane nephropathy is the most common cause of benign familial hematuria and follows autosomal dominant inheritance. 1
- Lupus nephritis, vasculitis (ANCA-associated), and other systemic glomerulonephritides can present with hematuria, proteinuria, and renal insufficiency. 1
Glomerular Indicators: Tea- or cola-colored urine, >80% dysmorphic RBCs on microscopy, red cell casts (pathognomonic), significant proteinuria (>500 mg/24h), and elevated creatinine all point to glomerular disease and warrant nephrology referral in addition to completing urologic evaluation. 1, 2
Systemic and Hematologic Causes
- Coagulopathies (hemophilia, von Willebrand disease) and anticoagulant/antiplatelet therapy (warfarin, DOACs, aspirin, clopidogrel) may unmask underlying urologic pathology but do not cause hematuria themselves—full evaluation must proceed regardless. 4, 1, 2
- Sickle cell disease causes hematuria through renal papillary necrosis and medullary infarction. 1, 2
- Thrombocytopenia and other platelet disorders can contribute to bleeding but require exclusion of structural urologic causes. 1
Critical Point: Anticoagulation is never an acceptable explanation for hematuria—these medications unmask pathology that requires investigation, and evaluation should proceed without delay. 4, 1
Metabolic and Anatomic Causes
- Hypercalciuria and hyperuricosuria are metabolic abnormalities that cause microscopic (and occasionally gross) hematuria and predispose to nephrolithiasis. 1
- Nutcracker syndrome (left renal vein compression) causes hematuria with variable proteinuria, diagnosed by Doppler ultrasound. 1
- Congenital urinary tract anomalies (horseshoe kidney, polycystic kidney disease, ureteropelvic junction obstruction) may present with hematuria, especially after minor trauma. 1
Non-Hematuria Mimics (Pseudohematuria)
- Myoglobinuria (rhabdomyolysis) produces red-brown urine with positive dipstick but no RBCs on microscopy. 4
- Hemoglobinuria (intravascular hemolysis) similarly causes dipstick positivity without intact RBCs. 4
- Food substances (beets, blackberries, rhubarb) and medications (rifampin, phenazopyridine, sulfa dyes) can discolor urine red without true hematuria. 1, 5
- Menstrual contamination in women can cause false-positive dipstick results; obtain catheterized specimen if clean-catch is unreliable. 4, 1
Diagnostic Threshold: Dipstick positivity has only 65–99% specificity—always confirm true hematuria with microscopic urinalysis showing ≥3 RBCs per high-power field on a properly collected specimen before initiating any workup. 4, 1
Age-Specific Considerations
- Pediatric patients: Glomerulonephritis (post-infectious, IgA nephropathy), congenital anomalies, and hypercalciuria are most common; malignancy is rare but Wilms tumor and rhabdomyosarcoma must be considered. 1, 2
- Adults >35–40 years: Malignancy risk increases sharply with age, particularly in men >60 years (high-risk category) and women >60 years. 1, 2
- Elderly men: BPH is common but bladder cancer remains the primary concern—cystoscopy is mandatory regardless of prostate size. 3
Risk Factors That Elevate Malignancy Concern
- Smoking history >30 pack-years is the strongest modifiable risk factor for urothelial carcinoma. 1, 3, 2
- Occupational exposure to benzenes, aromatic amines, or other chemicals/dyes (painters, hairdressers, rubber/textile workers) significantly increases bladder cancer risk. 1, 3, 2
- Irritative voiding symptoms (urgency, frequency, nocturia) without documented infection are high-risk features for urothelial malignancy. 1
- History of pelvic radiation or cyclophosphamide exposure increases bladder cancer risk. 1
Common Pitfalls to Avoid
- Never ignore gross hematuria even if self-limited—30–40% malignancy risk mandates urgent urologic referral within 24–48 hours. 4, 1
- Do not attribute hematuria to anticoagulation as the sole explanation—proceed with full evaluation regardless of medication use. 4, 1, 2
- Do not delay evaluation while treating presumed UTI—if hematuria persists 6 weeks after antibiotics, immediate urologic workup is required. 1
- Do not rely on imaging alone—cystoscopy is mandatory for all adults with gross hematuria to directly visualize bladder mucosa, as CT cannot exclude bladder cancer. 1
- Do not assume BPH explains hematuria in older men—gross hematuria from BPH must be proven through cystoscopy after excluding malignancy. 3