Microscopic Hematuria (2025)

See Original Guidelines

See Algorithm associated with this Guideline

See AUA Microscopic Hematuria Guidelines (2020)

See CUA Asymptomatic Microscopic Hematuria Guidelines 2008

• Literature search up to June 2024

Definitions

• Microscopic hematuria (MH): ≥ 3 RBCs per high powered field on microscopic examination of a single properly collected, urinary specimen
  • Given the intermittent nature of hematuria, only a single UA with ≥3 RBC/HPF is necessary to establish the presence of MH

Background

• Hematuria remains one of the most common urologic diagnoses
  • Estimated to account for >20% of urology evaluations
• Prevalence of MH among healthy volunteers: 2-30% depending on the specific population evaluated.

Causes of Hematuria (14)

Malignant	Non-malignant
Kidney Renal pelvis/ureter Bladder Prostate Urethra	Infection Inflammation Stones Benign prostatic hyperplasia (BPH) Benign tumor in urinary tract Congenital or acquired anatomic abnormalities Urethral strictures and diverticula Trauma Recent urological procedures/catheterization Medical renal disease Idiopathic

• Risk of urinary tract malignancy in patients with hematuria: 10%
  • 13% for patients with gross hematuria and 1-3% among patients with microscopic hematuria (MH)
  • Vast majority are bladder cancers

Diagnosis and Evaluation

UrologySchool.com Summary

1. History and Physical Exam (blood pressure and GU exam)
2. Labs
   1. Urine microscopy
   2. Renal function assessment
3. Upper tract imaging
   1. US for intermediate-risk
   2. CT urography for high-risk
4. Cystoscopy (intermediate- and high-risk)

History and Physical Exam

History

• Signs and Symptoms
  • Increases risk for malignant causes
    1. Higher degree of hematuria
    2. Persistence of hematuria
    3. History of gross hematuria
    4. Storage lower urinary tract symptoms
  • Increases risk for non-malignant causes
    1. Fever and dysuria (may indicate UTI)
    2. Flank pain (may indicate urinary tract stone)
    3. Voiding symptoms (may indicated prostatic hyperplasia or urethral stricture)
    4. Recent perineal trauma or GU instrumentation
    5. Menstrual and gynecologic history
• Risk factors for malignancy (8):
  1. Age
  2. Male sex
  3. Smoking
  4. Prior pelvic radiation therapy
  5. Prior cyclophosphamide/ifosfamide chemotherapy
  6. Family history of urothelial cancer or Lynch Syndrome
  7. Occupational exposures to benzene chemicals or aromatic amines (e.g., rubber, petrochemicals, dyes)
  8. Chronic indwelling foreign body in the urinary tract
• Past medical history
  • Hypertension, history of kidney disease, renal insufficiency, may indicate glomerular disease
    • If medical renal disease is suspected, refer patients for nephrologic evaluation. However, risk-based urologic evaluation should still be performed.
  • Gynecologic and non-malignant genitourinary causes of MH
    • In patients with findings suggestive of a gynecologic or non-malignant urologic etiology, clinicians should evaluate the patients with appropriate physical examination techniques and tests to identify such an etiology.
      • Patients suspected of having urolithiasis, urethral stricture disease, urethral diverticulum, or other non-malignant sources of MH should be evaluated appropriately to rule in or rule out these causes.
    • In patients diagnosed with gynecologic or non-malignant genitourinary sources of microhematuria, clinicians should repeat urinalysis following resolution of the gynecologic or non-malignant genitourinary cause. If microhematuria persists or the etiology cannot be identified, clinicians should perform risk-based urologic evaluation.
    • In patients with hematuria attributed to a urinary tract infection, clinicians should obtain a urinalysis with microscopic evaluation following treatment to ensure resolution of the hematuria.
      • If the MH does not resolve following treatment of the UTI, a risk-based urologic evaluation should be performed.
    • Microscopic hematuria may not resolve for several weeks to a few months following treatment of a gynecologic or non-malignant cause of MH, or treatment of a UTI; waiting ≥ 3 weeks after resolution of the non-malignant etiology and ≤ 3 months would be appropriate.
      • If MH persists or the etiology cannot be identified, perform risk-based urologic evaluation.
    • Causes of MH that persist and may not require intervention (3):
      1. BPH (enlarged prostate with surface vessels)
      2. Randall's plaques and non-obstructing nephrolithiasis
      3. Vaginal atrophy
      4. Interstitial cystitis
      5. Pelvic organ prolapse
      • In these cases, use careful judgment and shared decision-making to decide whether to pursue MH evaluation. Attention to the patient’s risk factors for urologic malignancy should inform these decisions.
• Medications
  • Urine may appear red in color from ingestion of certain drugs
  • MH in patients who are taking anti-coagulants requires the same evaluation evaluation regardless of the type or level of anti-coagulation therapy
• Diet
  • Urine may appear red in color from ingestion of certain foods

Physical Examination

• General
  • Blood pressure measurement
• Genitourinary examination
  • In females, examination of the external genitalia, introitus, and periurethral tissue may identify urethral pathology or other gynecologic pathology to explain the MH.

Laboratory

Urinalysis

Proper sample collection

• For most initial evaluations, a random midstream clean-catch collection is sufficient.
  • Patients should discard the initial 10 mL of voided urine in order to collect the midstream void.
• If a significant number of squamous cells are present in the sample, contamination is possible and a repeat specimen collection or catheterization should be considered.
  • Catheterization may be necessary in order to obtain an appropriate specimen in some patients such as
    • Obese female patients
    • Non-intact urinary tract
    • Use of Foley catheter, a suprapubic catheter, or who use intermittent catheterization.
• Females with concurrent menstruation should be reevaluated after its cessation or should undergo catheterization to determine if the blood is in fact present in the urine or is only noted as a result of vaginal contamination.
• Urine specimens collected immediately after prolonged recumbency (first void in morning) or the first voiding after vigorous physical or sexual activity should not be examined to assess for microhematuria.

Urine dipstick

• Detects the peroxidase activity of hemoglobin using benzidine
• Causes of false-positive dipstick (5):
  1. Myoglobinuria
  2. Dehydration
  3. Exercise
  4. Menstrual blood
  5. Povidone-iodine (betadine)§

• A positive dipstick merits microscopic examination of the urinary sediment, but does not warrant full evaluation unless microscopic evaluation confirms ≥3 RBC/HPF.

Urine microscopy

• Dysmorphic RBCs, cellular casts, and proteinuria may indicate glomerular disease
  • If medical renal disease is suspected, refer patients for nephrologic evaluation. However, risk-based urologic evaluation should still be performed.
• If <3 RBC/HPF but suspicious that the findings could reflect true MH, then repeat microscopic testing may be reasonable after assessing patient risk and preference.

Renal function assessment (serum creatinine/GFR)

Rationale (2):

1. Identify kidney disease
   • Abnormal renal function warrants evaluation to include establishing the etiology of renal dysfunction either as it relates to, or independent of, the cause of hematuria
2. Guide the choice of imaging modality, should that be deemed necessary based on patient risk
   • Renal dysfunction increases the risk of contrast or gadolinium radiologic studies and needs to be considered in the selection of these diagnostic procedures.

• NOT required in CUA guidelines

Urinary markers

• Urine-based tumor markers (CxBladder Resolve, NMP22 BladderChek, UroVysion FISH assay, Xpert® Bladder Cancer Detection) and urine cytology were developed to provide a non-invasive method to detect urothelial carcinoma
  • Negative predictive value >95% for cytology and urinary biomarkers
• Indications
  • Urine cytology and urine markers should not be routinely used in the initial evaluation of low/negligible- or high-risk patients (CUA Guidelines recommend cytology)
  • Urine cytology and urine markers should not be routinely used to decide whether to perform cystoscopy in the initial evaluation of low/negligible- or high-risk patients with microhematuria
  • Urine cytology and urine markers should not be routinely used as adjunctive tests in the setting of a normal cystoscopy.
    • While the current Guideline finds potential value in using cytology and UBTMs in patients with intermediate-risk MH as part of a shared decision-making, this does not extend as an adjunctive diagnostic test in addition to cystoscopy for the evaluation of patients with MH.
  • Urine cytology may be obtained for high-risk patients with equivocal findings on cystoscopic evaluation or those with persistent microhematuria and irritative voiding symptoms or risk factors for carcinoma in situ after a negative work up.
    • Cytology may have a role is in improving detection of CIS.
    • May be a role for cytology in adjudicating cases of high-risk patients with equivocal cystoscopic evaluation to decide whether to perform biopsy
    • There are instances in which clinical suspicion for CIS is sufficiently high that urinary cytology may be warranted as an adjunctive test

Imaging

Rationale (2):

1. Identify malignancies of the renal parenchyma and upper tract urothelium
2. Identify actionable non-malignant diagnoses of the kidney, collecting system, and ureters (e.g. stones)

Options

1. CT Urography
2. MR Urography
3. Renal US

Imaging modalities in MH

	CT Urography	MR Urography	Renal US
Advantages	Sensitive for renal cortical tumors and upper tract urothelial tumors Very sensitive for nephrolithiasis Provides extra-urinary information	Sensitive for renal cortical tumors and upper tract urothelial tumors Provides extra-urinary information Avoids ionizing radiation	Relatively less expensive Does not involve ionizing radiation Reasonable discrimination for cortical lesions
Disadvantages	Generally more expensive than renal US Ionizing radiation Options to minimize radiation exposure: Split bolus protocols Radiation dose adjustment for BMI Involves intravenous contrast Potential for false-positive findings	Low sensitivity for nephrolithiasis Inconvenience of the lengthy exam Cost Limited accessibility Involves intravenous contrast, risk of nephrogenic systemic fibrosis (NSF) In 2018, the American College of Radiology issued recommendations that relax the concern for NSF, particularly with the use of newer gadolinium agents (e.g., gadobutrol, gadoxetate), even in patients with low renal function. Potential for false-positive findings	Image quality is dependent on the operator and the patient’s body habitus Lower sensitivity for urothelial lesions, ureteral lesions, small solid renal lesions, and kidney stones
Contraindications	Chronic kidney disease Allergy to iodine-based contrast	Mobile metal implants Claustrophobia	None

Indications

• Intermediate-risk: US
• High-risk: CT urography (preferred)

Special Scenarios

• In patients with persistent or recurrent MH previously evaluated with renal US, consider additional imaging of the urinary tract
• In patients with MH who have a family history of renal cell carcinoma, a known genetic renal tumor syndrome, or a personal or family history of (or suspicious for) Lynch syndrome, upper tract imaging should be performed regardless of risk category.
• For MH during pregnancy, obtain renal US with consideration of multiphasic CT or MR urography after delivery.

Cystoscopy

Rationale

• CT urography or ultrasound have limited sensitivity for identifying bladder cancer

Options

• White light cystoscopy
  • Remains the standard for evaluation of MH
    • Reliability of WLC for the detection of flat lesions (i.e., carcinoma in situ [CIS]) is lower relative to papillary tumors, with a false-negative rate as high as 20%
• Blue light cystoscopy
  • Associated with improved detection of CIS and papillary tumors as well as reduction in disease recurrence compared with WLC in patients with bladder cancer.
  • The benefit of blue light cystoscopy in the evaluation of MH remains unknown
• Recommended for intermediate- and high-risk (CUA Guidelines say >40)

Risk Stratification

• Factors to consider (5):
  1. Urinalysis
  2. Age
  3. Smoking
  4. Risk factors for urothelial cancer

Risk Stratification Table

	Low/negligible	Intermediate (any of these criteria)	High (any of these criteria)
Risk of malignancy	0-0.4%	0.2-3%	1-6%
Number of criteria patient must meet	All	One or more	One or more
UA	3-10 RBC/HPF	11-25 RBC/HPF	>25 RBC/HPF
Alternative criteria for degree of hematuria		Previously low/negligible-risk patient with no prior evaluation and 3-25 RBC/HPF* on repeat urinalysis	History of gross hematuria
Age for women	<60 years	≥60 years	Women should not be categorized as high-risk solely based on age
Age for men	<40 years	40-59 years	≥60 years
Smoking	Never smoker OR <10 pack years	10-30 pack years	>30 pack years
Risk factors for urothelial cancer (see above)	None	Any	One or more plus any high-risk feature

• Recommended investigations based on risk stratification (4)
  • Low/negligible-risk
    • Obtain repeat urinalysis within 6 months rather than perform immediate cystoscopy or imaging
      • If the repeat UA shows
        • No evidence of MH, then no further evaluation is needed at this time.
          • In that case, further evaluation would only be merited if new symptoms, more severe MH on subsequent opportunistic testing, or GH develop.
        • Persistent MH, patients should be reclassified as intermediate- or high-risk based on repeat urinalysis.
      • If the patient experiences recurrence of similar level of MH (3-10 RBCs/HPF) on subsequent opportunistic testing, further evaluation may be considered in a shared decision-making process.
  • Intermediate-risk
    • Recommend cystoscopy and renal ultrasound
      • In appropriately counseled intermediate-risk patients who want to avoid cystoscopy and accept the risk of forgoing direct visual inspection of the bladder urothelium, clinicians may offer urine cytology or validated urine-based tumor markers (CxBladder Resolve, NMP22 BladderChek, UroVysion FISH assay, Xpert® Bladder Cancer Detection) to facilitate the decision regarding utility of cystoscopy. Renal and bladder ultrasound should still be performed in these cases
        • For patients with intermediate-risk microhematuria who do not undergo cystoscopy based on urinary marker results, clinicians should obtain a repeat urinalysis within 12 months. Such patients with persistent microhematuria should then undergo cystoscopy
          • For patients with a negative follow-up UA, clinicians should engage in shared decision-making regarding whether to repeat UA in the future.
  • High-risk
    • Recommend cystoscopy and CT urography (preferred)
      • If CT contraindicated, consider MR urography; if both CT and MR urography contraindicated, consider retrograde pyelography with non-contrast axial imaging or US
      • CUA Guidelines recommend US

Gross hematuria

• Should be evaluated with (3)
  1. Cystoscopy
  2. Upper tract imaging
  3. Urinary cytology

Follow-up

• In patients with a negative hematuria evaluation, engage in shared decision-making regarding whether to repeat urinalysis in the future.
  • Most patients who have an appropriate risk-stratified negative hematuria evaluation do not require ongoing urologic monitoring and may be safely discharged from the urology clinic after shared decision-making and discussion of the best available evidence.
    • After a negative MH evaluation and in the absence of a change in clinical condition, (i.e., GH, new symptoms) repeated evaluation has minimal diagnostic yield.
      • Patients with a past negative MH evaluation do not appear to be at increased risk of developing malignancy compared to a patient without a history of MH.
  • In situations where ongoing follow up after a negative hematuria evaluation is desired, obtain a repeat UA with microscopy (optimal timing based on shared-decision making).
    • Select patients (for example those with multiple risk factors for malignancy or a heavy smoking history) may benefit from and/or request follow-up after a negative hematuria evaluation.
  • 2000 AUA MH guidelines recommended repeat UA within 12 months
• For patients with a prior negative hematuria evaluation who undergo repeat urinalysis and are found to have
  • Subsequent negative urinalysis, may discontinue further evaluation for MH.
  • Persistent or recurrent MH, engage in shared decision-making regarding the need for additional evaluation.
    • Factors that may be considered are time since the initial (or prior) negative evaluation, presence of other risk factors, and overall risk stratification.
• For patients with a prior negative hematuria evaluation who develop gross hematuria, significant increase in degree of microhematuria, or new urologic symptoms, initiate further evaluation.
  • The low overall risk of malignancy in this population must again be acknowledged; therefore, a uniform approach to investigation in this setting cannot be mandated.
• Ultimately, clinicians’ judgement and patients’ preferences are critical in the shared decision-making process regarding whether to repeat the urinalysis in the future or to release the patient from care.

References

• Barocas, Daniel A., et al. "Updates to Microhematuria: AUA/SUFU Guideline (2025)." Journal of Urology (2025): 10-1097.