Urine

Hematuria in Adults

search

Hematuria in Adults, Microscopic Hematuria in Adults, Hematuria

  • See Also
  1. Pediatric Hematuria
  2. Microscopic Hematuria
  3. Microscopic Hematuria Causes in Adults
  4. Gross Hematuria
  • Definitions
  1. Hematuria
    1. Blood in urine (either gross or microscopic)
    2. Significant Hematuria: 3 Red Blood Cells/HPF or more
  • Epidemiology
  1. Microhematuria Prevalence: >2.4% of healthy patients
    1. Microhematuria accounts for 20% of urology visits
  2. Malignancy risk based on Hematuria type
    1. Microscopic Hematuria: 5% malignancy risk
    2. Gross Hematuria: 30-40% malignancy risk
  3. Malignancy risk increases over age 35-40 years old
    1. Age under 40 years with Hematuria
      1. Healthy men with Hematuria at one time: 39%
    2. Age over 40 years with Hematuria
      1. Bladder CancerIncidence: 2.5%
  • Risk factors
  • Urologic Malignancy Risks (suggestive of significant cause of Hematuria)
  1. Tobacco Abuse
  2. Occupational exposures (leather dye, Rubber, tire)
    1. Trichloroethylene
    2. Benzenes
    3. Aromatic amines
  3. Chemotherapy agents (e.g. Alkylating Agents: Cyclophosphamide, Ifosfamide)
  4. Gross Hematuria
  5. Age over 35 years
  6. Male gender
  7. Pelvic Radiation Therapy history
  8. Chronic indwelling foreign body
  9. Voiding symptoms suggestive of irritation
  10. Chronic Urinary Tract Infection history
  11. Analgesic overuse
  12. Family History at high risk or urologic malignancy
    1. Lynch Syndrome (or personal history)
    2. Renal Cell Carcinoma
    3. Genetic renal tumor syndromes
      1. Birt-Hogg-Dube Syndrome
      2. Hereditary Leiomyomatosis Renal Cell Cancer
      3. Hereditary papillary Renal Cell Carcinoma
      4. Tuberous sclerosis
      5. von Hippel-Lindau Disease
  • Risk Factors
  • AUA Microhematuria Risk Stratification (drives evaluation protocol)
  1. Low Risk if ALL criteria met
    1. Age <40 years in Men (<60 years in Women) AND
    2. Never smoked (or <10 py history) AND
    3. Single Urinalysis with 3-10 RBCs/hpf AND
    4. No risk factors for urothelial cancer
  2. Intermediate Risk if ANY criteria met
    1. Age 40 to 59 years in Men (>60 years in Women) OR
    2. Smoked 10-30 pack years OR
    3. Single Urinalysis with 11-25 RBCs/hpf OR
    4. Repeat, confirmatory Urinalysis with 3-10 RBCs/hpf AND otherwise low risk patient OR
    5. Other risk factors for urothelial cancer
  3. High Risk if ANY criteria met
    1. Age >=60 years OR
    2. Smoked >30 pack years OR
    3. Single Urinalysis with >25 RBCs/hpf OR
    4. Gross Hematuria OR
    5. One or more risks for urothelial cancer combined with high risk features
  4. References
    1. Barocas (2020) J Urol 204(4): 778-86 [PubMed]
    2. Barocas (2025) J Urol 213(5): 547-57 [PubMed]
  • Causes
  1. See Adult Microscopic Hematuria Causes
  2. See Medication Causes of Hematuria
  3. See Pediatric Hematuria
  4. See Gross Hematuria
  • Exam
  1. Blood Pressure
  2. Men
    1. Genitourinary examination
    2. Rectal Exam for Prostate size and nodularity
  3. Women: Pelvic examination
    1. Urethral mass
    2. Diverticula
    3. Atrophic Vaginitis
    4. Uterine bleeding
  • Labs
  • All Hematuria cases
  1. Renal Function tests
    1. Serum Creatinine
    2. Blood Urea Nitrogen
  2. Urinalysis with microscopic exam
    1. See Microscopic Hematuria
    2. Obtain a clean-catch midstream urine
    3. Inadequate sample (contaminated with vaginal contents)
      1. Squamous epithelial cells >5/hpf
    4. Consider catheterized specimen
      1. Anatomy interferes with collection (e.g. Vaginal Atrophy, Pelvic Organ Prolapse)
      2. Differentiate urologic source of bleeding from gynecologic source
    5. Signs of renal disease
      1. Glomerular disease
        1. Urine brown (Coca-Cola color)
        2. Microscopy
          1. Red Blood Cell Casts
          2. Dysmorphic Red Blood Cells
        3. Proteinuria
      2. Extraglomerular disease
        1. Clots of blood
  • Labs
  • Other tests to consider
  1. Voided urine cytology (or validated urine-based Tumor Markers)
    1. No longer recommended for routine Hematuria evaluation
      1. Cystoscopy has higher Test Sensitivity than either urine cytology or Bladder Cancer detection markers
      2. Defer cytology and Bladder Cancer detection marker testing to Urology
      3. Avoid in low risk and high risk patients (see risk stratification as above)
        1. May be used in intermediate risk patients who refuse cystoscopy
    2. Protocol
      1. Obtain three serial first-morning specimens
      2. Evaluate for transitional cell cancer
    3. Bladder Cancer detection markers (no evidence for benefit over standard cytology or cystoscopy)
      1. Fluorescent in situ hybridization (FISH)
      2. Nuclear matrix Protein 22 Test
      3. Bladder tumor Antigen stat test
      4. Urinary Bladder cancer Antigen
  2. Nephropathy or Glomerulonephritis evaluation
    1. Urine Protein to Creatinine Ratio
    2. Antinuclear Antibody
    3. ASO Titer
    4. Serum Complement (C3, C4, C50)
  3. Prostate
    1. Prostate Specific Antigen
  4. Coagulation Factors
    1. INR (ProTime, PT)
    2. Partial Thromboplastin Time (PTT)
  5. Miscellaneous tests
    1. Collect 24 hour Urine Calcium
    2. Collect 24 hour Urine Uric Acid
  6. Urinalysis of "Three Glass Test" (listed for historical purposes)
    1. Glass 1: Initiation of urine stream
      1. Hematuria in Glass 1 only suggests Urethral source
    2. Glass 2: Midstream urine
      1. Hematuria in all glasses suggests Bladder or renal
    3. Glass 3: Termination of urine stream
      1. Hematuria in Glass 3 only suggests Prostate source
  • Imaging
  • Upper Urinary Tract
  1. Indications (see risk stratification and risk factors above)
    1. Microscopic Hematuria with high risk of malignancy
    2. Gross Hematuria
    3. Family History at high risk or urologic malignancy
  2. Multiphase CT Urogram (preferred in high risk cases)
    1. See CT Urogram for details
    2. CT Abdomen and Pelvis with 3 phases of contrast
      1. Non-contrast stone evaluation
      2. Nephrogram
      3. Delayed phase of the lower urinary tract
  3. CT of the Abdomen and Pelvis without contrast (stone CT)
    1. Initial imaging in suspected Ureteral Stone
    2. Alternative to Multiphase CT Urogram when contraindicated in high risk patients
  4. Renal Ultrasound
    1. Defines anatomy, as well as signs of glomerular disease and Renal Cysts
    2. Indicated upper tract imaging in intermediate risk patients (in combination with cystoscopy)
    3. CT Urogram is typically preferred (if not contraindicated) over Ultrasound in high risk patients
      1. Combine with retrograde pyelography in high risk patients unable to undergo CT Urogram
  5. MRI Urography
    1. Indicated where CT Urogram is contraindicated (e.g. Pregnancy, Children)
    2. Identifies urothelial cancer, Nephrolithiasis and renal tumors
    3. Alternative to Multiphase CT Urogram when contraindicated in high risk patients
  • Diagnostics
  • Lower Tract
  1. Cystoscopy
    1. Extraglomerular source of Hematuria (Bladder and Urethra)
    2. Indications
      1. Intermediate and high risk patients (see protocol below)
      2. Gross Hematuria (without obvious source, e.g. Ureteral Stone)
      3. Microscopic Hematuria with moderate to high risk of malignancy
  • Evaluation
  • Protocol
  1. Approach: General
    1. Consider non-urinary source (e.g. vagina, Rectum)
    2. Gross Hematuria should be thoroughly evaluated including urologic Consultation
    3. Evaluation is the same regardless of Anticoagulation or antiplatelet use
    4. Evaluation focuses on 3 key sources
      1. Genitourinary cancer
      2. Renal disease
      3. Gynecological disorders
    5. Confirm adequate sample
      1. See Microscopic Hematuria
      2. Squamous epithelial cells >5/hpf suggests vaginal contaminant
      3. Urine Dipstick alone is inadequate due to high False Positive Rate
        1. Urine microscopy is needed on each sample
        2. False Positives occur with Hemoglobinuria, Myoglobinuria and alkalotic urine (pH >9)
        3. False Negatives occur with Vitamin C Supplementation
    6. Indications for Urologic Consultation regardless of protocol below
      1. Gross Hematuria
      2. Anticoagulant use with asymptomatic Microscopic Hematuria
  2. Approach: Risk-Based Management (See Risk Stratification above)
    1. Low Risk
      1. Repeat Microscopic Urinalysis within 6 months (without other Microscopic Hematuria workup)
      2. If Microscopic Urinalysis Hematuria persists on repeat sample, reclasify patient as intermediate or high risk
    2. Intermediate Risk
      1. Renal and Bladder Ultrasound AND
      2. Cystoscopy (preferred)
      3. Alternative to cystoscopy (for those refusing cystoscopy)
        1. Counsel on risks of missed significant pathology without direct visualization of cystoscopy
        2. Urine cytology and/or validated urine-based Tumor Markers (90-95% Negative Predictive Value)
        3. Repeat Urinalysis with microscopy within 12 months, and perform cystoscopy if persistent Microhematuria
    3. High Risk
      1. Cystoscopy AND
      2. Multiphase CT Urography (preferred)
      3. Alternatives if CT Urography is contraindicated (e.g. IV contrast)
        1. MR Urography
        2. Non-contrast Axial CT ("stone run CT")
        3. Renal Ultrasound and retrograde pyelography
  3. Step 1: Initial evaluation of isolated Microhematuria
    1. Indications
      1. Urine RBC 3/hpf or more OR
      2. Urine RBC < 3/hpf on 2 samples
        1. Incidental Microscopic Hematuria followed with 3 urine samples at 6 week intervals
        2. No further evaluation if Hematuria found only on one of 4 samples
    2. Protocol
      1. Evaluate and treat for secondary cause
        1. Urinary Tract Infection
        2. Exercise Hematuria (march Hematuria, e.g. distance runners)
        3. Menses
        4. Genitourinary infection (including sexually tramsmitted infection)
        5. Recent urologic procedure
        6. Trauma
        7. Hematologic causes (consider Coagulopathy)
      2. Repeat Urinalysis with microscopy at 6 weeks following treatment
        1. Positive: Go to Step 2
        2. Negative: No further evaluation required unless symptomatic
  4. Step 2: Evaluate for renal cause
    1. Indications: Nephropathy (IgA Nephropathy, Alport Syndrome, Benign familial Hematuria)
      1. Proteinuria (1+ or greater on dipstick)
      2. Serum Creatinine elevated
      3. Dysmorphic Red Blood Cells or Red cell casts
        1. Suggests glomerular cause
        2. No dysmorphic cells suggests interstitial cause
    2. Protocol (if indicated above, otherwise continue to step 3)
      1. Serum Creatinine with calculated GFR (obtain regardless of urine sediment)
      2. Urine Protein to Creatinine Ratio
      3. Nephrology Consultation
  5. Step 3: Evaluate for urologic malignancy with imaging
    1. CT Urogram (preferred) OR
    2. Alternative imaging modality
      1. Indications
        1. Low risk of urologic malignancy (see above)
        2. Contrast Media Allergy
        3. Poor Renal Function
        4. Radiation contraindication (e.g. young age)
      2. Modalities (less optimal)
        1. MR Urography or MRI Abdomen and Pelvis
        2. Renal Ultrasound
        3. Non-contrast CT Abdomen and Pelvis (Stone protocol)
        4. Retrograde pyelogram
  6. Step 4: Urologic Evaluation
    1. Protocol
      1. Urology Consultation
      2. Cystoscopy
      3. Consider urine cytology (3 first morning voids)
        1. Obtain only if recommended by local urology consultants
    2. Positive findings on cystoscopy, imaging or labs
      1. Management per urology
    3. Negative evaluation
      1. Go to step 5 below
  7. Step 5: Surveillance following negative Hematuria evaluation
    1. Repeat Urinalysis annually for 2 years following initial evaluation
    2. Positive Urinalysis on either of the 2 rechecks
      1. Repeat Urinalysis, imaging and cystoscopy within 3-5 years
    3. Negative Urinalysis on both of the rechecks
      1. No further testing required unless symptomatic
      2. Risk of future urologic malignancy <1%
  • References
  1. Barocas (2025) J Urol 213(5): 547-57 [PubMed]
  2. Cohen (2003) N Engl J Med 348:2330-8 [PubMed]
  3. Davis (2012) J Urol 188(6): 2473-81 [PubMed]
  4. Grossfield (2001) Am Fam Physician 63(6):1145-54 [PubMed]
  5. Grossfield (1998) Urol Clin North Am 25:661-76 [PubMed]
  6. Sharp (2014) Am Fam Physician 90(8): 542-7 [PubMed]
  7. Sharp (2013) Am Fam Physician 88(11): 747-54 [PubMed]
  8. Sutton (1990) JAMA 263:2475-80 [PubMed]