Causes of Hematuria and Recommended Workup

Blood in the urine (hematuria) can arise from anywhere along the urinary tract—from the kidneys to the bladder—and requires systematic evaluation to distinguish benign causes from serious pathology, including malignancy.

Classification of Hematuria

Gross (macroscopic) hematuria is visible blood that can be seen with the naked eye and carries a 30–40% risk of underlying malignancy, mandating urgent urologic evaluation even if self-limited. 1
Microscopic hematuria is defined as ≥3 red blood cells per high-power field (RBC/HPF) on microscopic examination of properly collected urine specimens. 1, 2
Dipstick testing alone has only 65–99% specificity and can yield false positives from myoglobin, hemoglobin, menstrual blood, or dietary substances; therefore, microscopic confirmation is mandatory before initiating any workup. 1, 3

Major Categories of Causes

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. 1
Renal cell carcinoma and transitional cell carcinoma of the upper urinary tract are also significant urologic malignancies detected during hematuria evaluation. 1, 4
Risk factors for urologic malignancy include age >35–40 years, smoking history >30 pack-years, occupational exposure to benzenes or aromatic amines, history of gross hematuria, and irritative voiding symptoms without infection. 1, 3

Urolithiasis (Kidney and Ureteral Stones)

Urinary calculi are a common cause of both microscopic and macroscopic hematuria, often presenting with flank pain. 5, 1
Unenhanced CT imaging is the gold standard for detecting stones, as it identifies calculus disease with high sensitivity. 4

Urinary Tract Infection (UTI)

UTI is a common cause of hematuria, characterized by dysuria, urgency, frequency, fever, and the presence of white blood cells and micro-organisms in urine. 5, 1
Hematuria should resolve after appropriate antibiotic treatment; persistence of hematuria 6 weeks after treatment warrants full urologic evaluation. 3, 2

Benign Prostatic Hyperplasia (BPH)

BPH is a common benign cause of hematuria in older men, but does not exclude concurrent malignancy; gross hematuria from BPH must be proven through appropriate evaluation. 1

Trauma

Trauma to the kidneys or lower urinary tract can cause hematuria; post-traumatic macroscopic hematuria requires contrast-enhanced CT to assess the extent of renal or urinary tract injury. 5, 1

Renal/Glomerular Causes

Glomerulonephritis

Post-infectious glomerulonephritis and IgA nephropathy are common glomerular causes of hematuria. 5, 1
Tea-colored or cola-colored urine, proteinuria >2+ on dipstick, >80% dysmorphic RBCs, and red blood cell casts on microscopy strongly suggest a glomerular source. 5, 1

Alport Syndrome

Alport syndrome is a hereditary nephritis associated with hearing loss and ocular abnormalities; audiogram and slit-lamp examination should be performed if suspected. 5, 1

Thin Basement Membrane Nephropathy (TBMN)

TBMN is an autosomal dominant condition and the most common cause of benign familial hematuria; screening first-degree relatives' urine may be useful. 1

Other Nephropathies

Lupus nephritis, vasculitis, and interstitial renal disease (including drug-induced interstitial disease or analgesic nephropathy) can cause hematuria. 5, 1

Metabolic and Anatomic Causes

Hypercalciuria and hyperuricosuria are metabolic abnormalities causing microscopic hematuria, sometimes with mild proteinuria, and may lead to nephrolithiasis; a spot urine calcium-to-creatinine ratio is the preferred initial test. 1
Nutcracker syndrome (left renal vein compression) causes hematuria with variable proteinuria and is diagnosed by ultrasound with Doppler. 1

Systemic and Other Causes

Vigorous exercise can cause transient hematuria that resolves after cessation of activity. 1, 3
Menstruation can contaminate urine samples in women, leading to false-positive results; obtain a catheterized specimen if clean-catch is unreliable. 1
Medications such as anticoagulants and antiplatelet agents do not cause hematuria but may unmask underlying pathology; evaluation must proceed regardless of medication use. 1, 3
Coagulopathies (e.g., hemophilia) and sickle cell disease can cause hematuria due to bleeding disorders or renal papillary necrosis. 5, 1

Recommended Workup

Step 1: Confirm True Hematuria

Obtain a microscopic urinalysis on a properly collected clean-catch midstream urine specimen and verify ≥3 RBC/HPF on at least two of three specimens before initiating any further workup. 1, 3
Exclude pseudohematuria (myoglobinuria, hemoglobinuria, menstrual contamination, food substances, or medications coloring the urine). 5, 1

Step 2: Exclude Transient Benign Causes

Rule out recent vigorous exercise, sexual activity, viral illness, trauma, and menstruation; repeat urinalysis 48 hours after cessation of the suspected cause. 1, 3
If UTI is suspected, obtain urine culture before antibiotics, treat appropriately, and repeat urinalysis 6 weeks after treatment to confirm resolution. 3, 2

Step 3: Distinguish Glomerular from Non-Glomerular Sources

Glomerular Indicators (Nephrology Referral)

>80% dysmorphic RBCs or red blood cell casts on urinary sediment (pathognomonic for glomerular disease). 1, 3
Significant proteinuria (protein-to-creatinine ratio >0.5 g/g or >500 mg/24 hours). 1, 3
Elevated serum creatinine or declining renal function. 1, 3
Hypertension accompanying hematuria and proteinuria. 1, 3
Tea-colored or cola-colored urine. 5, 1

Non-Glomerular Indicators (Urologic Evaluation)

>80% normal-shaped (isomorphic) RBCs with minimal or no proteinuria. 1
Absence of dysmorphic RBCs, red cell casts, or significant proteinuria. 1, 3

Step 4: Risk Stratification for Urologic Malignancy

High-Risk Features (Require Full Urologic Evaluation: Cystoscopy + CT Urography)

Age ≥60 years (both men and women). 1
Smoking history >30 pack-years. 1
Any history of gross hematuria, even if self-limited. 1
Occupational exposure to benzenes, aromatic amines, or other bladder carcinogens. 1, 3
Irritative voiding symptoms (urgency, frequency, dysuria) without documented infection. 1
Microscopic hematuria >25 RBC/HPF. 1

Intermediate-Risk Features (Shared Decision-Making for Cystoscopy/Imaging)

Age 40–59 years (men) or 50–59 years (women). 1
Smoking history 10–30 pack-years. 1
Microscopic hematuria 11–25 RBC/HPF. 1

Low-Risk Features (May Defer Extensive Imaging)

Age <40 years (men) or <50 years (women). 1
Never smoker or <10 pack-years. 1
Microscopic hematuria 3–10 RBC/HPF. 1

Step 5: Complete Urologic Evaluation (for High-Risk or Persistent Hematuria)

Upper Tract Imaging

Multiphasic CT urography (unenhanced, nephrographic, and excretory phases) is the preferred imaging modality, with 96% sensitivity and 99% specificity for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis. 1, 4, 2
When CT is contraindicated (e.g., severe renal insufficiency or contrast allergy), MR urography or renal ultrasound with retrograde pyelography may be used as alternatives. 1, 2

Lower Tract Evaluation

Flexible cystoscopy is mandatory for all patients with gross hematuria and for microscopic hematuria patients ≥40 years or with high-risk features; it provides direct visualization of the bladder mucosa, urethra, and ureteral orifices. 1, 2
Flexible cystoscopy is preferred over rigid cystoscopy because it causes less pain with equivalent or superior diagnostic accuracy. 1, 2

Urine Cytology

Voided urine cytology should be obtained in high-risk patients (age >60 years, smoking >30 pack-years, occupational exposures) to detect high-grade urothelial carcinomas and carcinoma in situ. 1, 2

Step 6: Laboratory Evaluation

Serum creatinine and BUN to assess renal function. 5, 1
Complete blood count with platelets to evaluate for coagulopathy. 5, 1
Spot urine protein-to-creatinine ratio to quantify proteinuria. 1, 3
Urine culture if infection is suspected, preferably before antibiotics. 1, 2
Complement levels (C3, C4), ANA, and ANCA testing if glomerulonephritis or vasculitis is suspected. 1

Step 7: Follow-Up Protocol for Negative Initial Evaluation

If the complete workup is negative but hematuria persists, repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit. 1, 3
After two consecutive negative annual urinalyses, further testing is unnecessary. 1
Immediate re-evaluation is warranted if gross hematuria develops, significant increase in microscopic hematuria occurs, new urologic symptoms appear, or development of hypertension, proteinuria, or evidence of glomerular bleeding. 1, 3

Common Pitfalls to Avoid

Never ignore gross hematuria, even if self-limited, due to the 30–40% malignancy risk; urgent urologic referral is mandatory. 1, 6
Do not attribute hematuria to anticoagulation or antiplatelet therapy without completing the full urologic workup; these medications may unmask underlying pathology but do not cause hematuria. 1, 3
Do not rely solely on dipstick testing; confirm with microscopic urinalysis showing ≥3 RBC/HPF before initiating workup. 1, 3
Do not delay evaluation in patients >35–40 years with confirmed hematuria, even if a benign cause is suspected. 1, 2
Glomerular features do not eliminate the need for urologic evaluation; malignancy can coexist with medical renal disease, so both evaluations should be completed. 1

Age-Specific Considerations

Children

Isolated microscopic hematuria without proteinuria or dysmorphic RBCs in children is unlikely to represent clinically significant renal disease and does not require imaging. 5, 1
Renal ultrasound is the preferred modality in children to assess kidney anatomy, size, and position before potential renal biopsy. 5, 1
Gross hematuria in children requires renal and bladder ultrasound to exclude nephrolithiasis, anatomic abnormalities, and rarely renal or bladder tumors. 1

Adults

In adults >35–40 years, malignancy is a significant risk factor, and cystoscopy and upper urinary tract imaging (CT urography) are recommended for all patients with gross hematuria and most with microscopic hematuria. 1, 2

Elderly Patients

Males ≥60 years are automatically classified as high-risk and require both cystoscopy and CT urography regardless of other factors. 1
Women ≥60 years with any additional risk factor (e.g., smoking, gross hematuria, >25 RBC/HPF) also require full urologic evaluation. 1, 6

What are the causes of hematuria and the recommended workup?

Help us tailor your experience