Hematuria in Adults

Aka: Hematuria in Adults, Hematuria

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II. Definitions

  1. Hematuria
    1. Blood in urine (either gross or microscopic)
    2. Significant Hematuria: 3 Red Blood Cells/HPF or more

III. Epidemiology

  1. Malignancy risk based on Hematuria type
    1. Microscopic Hematuria: 5% malignancy risk
    2. Gross Hematuria: 30-40% malignancy risk
  2. 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%

IV. 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)
  4. Gross Hematuria
  5. Age over 35 years
  6. Male gender
  7. Pelvic irradiation history
  8. Chronic indwelling foreign body
  9. Voiding symptoms suggestive of irritation
  10. Chronic Urinary Tract Infection history
  11. Analgesic overuse

V. Causes

  1. See Adult Microscopic Hematuria Causes
  2. See Medication Causes of Hematuria
  3. See Pediatric Hematuria
  4. See Gross Hematuria

VI. 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

VII. 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. Inadequate sample (contaminated with vaginal contents)
      1. Squamous epithelial cells >5/hpf
    3. 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

VIII. Labs: Other tests to consider

  1. Voided urine cytology
    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
    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

IX. Diagnosis

  1. Helical CT Urogram (preferred)
    1. See CT Urogram for details
    2. CT Abdomen and Pelvis with three phases of contrast
      1. Non-contrast stone evaluation
      2. Nephrogram
      3. Delayed phase of the lower tract
  2. Renal Ultrasound
    1. Defines anatomy
    2. Signs of glomerular disease and Renal Cysts
    3. CT Urogram is usually preferred over Ultrasound
  3. Intravenous Pyelogram
    1. Suspected Nephrolithiasis
  4. Cystoscopy
    1. Extraglomerular source of Hematuria
  5. MRI Urography
    1. Indicated where CT Urogram is contraindicated (e.g. Pregnancy, Children)
    2. Identifies urothelial cancer, Nephrolithiasis and renal tumors

X. 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. 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. False Positives occur with Hemoglobinuria, Myoglobinuria and alkalotic urine (pH >9)
        2. False Negatives occur with Vitamin C Supplementation
    4. Indications for Urologic Consultation regardless of protocol below
      1. Gross Hematuria
      2. Anticoagulant use with asymptomatic Microscopic Hematuria
  2. Step 1: Initial evaluation of isolated Hematuria
    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 treat 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
  3. 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
  4. 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
  5. 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
  6. 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%

XI. References

  1. Cohen (2003) N Engl J Med 348:2330-8 [PubMed]
  2. Davis (2012) J Urol 188(6): 2473-81 [PubMed]
  3. Grossfield (2001) Am Fam Physician 63(6):1145-54 [PubMed]
  4. Grossfield (1998) Urol Clin North Am 25:661-76 [PubMed]
  5. Sharp (2014) Am Fam Physician 90(8): 542-7 [PubMed]
  6. Sharp (2013) Am Fam Physician 88(11): 747-54 [PubMed]
  7. Sutton (1990) JAMA 263:2475-80 [PubMed]

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