Editing Microscopic Hematuria (2020 AUA Guidelines)

'''See [https://pubmed.ncbi.nlm.nih.gov/32698717/ Original Guidelines]'''

'''See [[CUA: Asymptomatic Microscopic Hematuria (2008)|CUA Asymptomatic Microscopic Hematuria Guidelines 2008]]'''

See [https://www.youtube.com/watch?v=FY-MAQE68dY Video Review of 2020 AUA Guidelines on Microscopic Hematuria]

== Background ==

* '''<span style="color:#ff0000">Causes of hematuria (14):</span>'''
*# '''<span style="color:#ff0000">Malignancy:</span>''' 
*##'''<span style="color:#ff0000">Kidney</span>'''
*##'''<span style="color:#ff0000">Renal pelvis/ureter</span>'''
*##'''<span style="color:#ff0000">Bladder</span>'''
*##'''<span style="color:#ff0000">Prostate</span>'''
*##'''<span style="color:#ff0000">Urethra</span>'''
*# '''<span style="color:#ff0000">Non-oncologic</span>'''
*##'''<span style="color:#ff0000">Infection</span>'''
*## '''<span style="color:#ff0000">Inflammation</span>'''
*## '''<span style="color:#ff0000">Stones</span>'''
*## '''<span style="color:#ff0000">Benign prostatic hyperplasia (BPH)</span>'''
*## '''<span style="color:#ff0000">Benign tumor in urinary tract</span>'''
*##'''<span style="color:#ff0000">Congenital or acquired anatomic abnormalities</span>'''
*## '''<span style="color:#ff0000">Urethral strictures and diverticula</span>'''
*## '''<span style="color:#ff0000">Trauma</span>'''
*## '''<span style="color:#ff0000">Recent urological procedures/catheterization</span>'''
* '''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
* Prevalence of MH among healthy volunteers: 2-30% depending on the specific population evaluated.
* '''<span style="color:#ff0000">Urine dipstick</span>'''
** Detects the peroxidase activity of hemoglobin using benzidine
** '''<span style="color:#ff0000">Causes of false-positive dipstick (5):</span>'''
**# '''<span style="color:#ff0000">Myoglobinuria</span>'''
**# '''<span style="color:#ff0000">Dehydration</span>'''
**# '''<span style="color:#ff0000">Exercise</span>'''
**# '''<span style="color:#ff0000">Menstrual blood</span>'''
**# '''<span style="color:#ff0000">Povidone-iodine (betadine)[https://pubmed.ncbi.nlm.nih.gov/4032677/ §]</span>'''
* '''Urine may appear red in color from ingestion of certain foods and drugs'''
* '''<span style="color:#ff0000">Definition of microscopic hematuria: ≥ 3 RBCs per high powered field on microscopic examination of a single properly collected, urinary specimen. (CUA Guidelines recommend 2 positive samples)</span>'''
** '''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 and patients with a non-intact urinary tract, a 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.'''
** '''<span style="color:#ff0000">A positive dipstick merits microscopic examination of the urinary sediment, but does not warrant full evaluation unless microscopic evaluation confirms ≥3 RBC/HPF.</span>'''
*** 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.
*'''Proper Sample Collection'''
**'''For most initial evaluations, a random midstream clean-catch collection is sufficient.''' 
***Patients should be instructed to discard the initial 10 mL of voided urine into the toilet in order to collect the midstream void
**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.

== Diagnosis and Evaluation ==

=== <span style="color:#ff0000">Risk stratification</span> ===

* '''<span style="color:#ff0000">Factors to consider (5):</span>'''
*# '''<span style="color:#ff0000">Age</span>'''
*# '''<span style="color:#ff0000">Smoking</span>'''
*# '''<span style="color:#ff0000">Urinalysis</span>'''
*# '''<span style="color:#ff0000">Risk factors for urothelial cancer</span>'''
*# '''<span style="color:#ff0000">Gross hematuria</span>'''

{| class="wikitable"
|
|'''<span style="color:#ff0000">Low (meets all criteria)'''
|'''<span style="color:#ff0000">Intermediate (any of these criteria)'''
|'''<span style="color:#ff0000">High (any of these criteria)'''
|-
|'''Age'''
|
* Females age <50 years
* Males age <40 years
|
* Females age 50-59 years
* Males age 40-59 years
|
* Females or Males ≥60 years
|-
|'''Smoking'''
|Never smoker OR <10 pack years
|10-30 pack years
|>30 pack years
|-
|'''UA'''
|3-10 RBC/HPF on a single urinalysis
|
* 11-25 RBC/HPF on a single urinalysis OR
* Low-risk patient with no prior evaluation and 3-10 RBC/HPF on repeat urinalysis
|>25 RBC/HPF on a single urinalysis
|-
|'''Risk factors for urothelial cancer (see below)'''
|None
|Yes
|
|-
|'''Gross hematuria'''
|
|
|Yes
|}

* '''<span style="color:#ff0000">Recommended investigations based on risk stratification (4)</span>'''
*# '''<span style="color:#ff0000">History and Physical Exam (all patients)</span>'''
*# '''<span style="color:#ff0000">Laboratory: serum Cr and GFR (all patients);</span> urine cytology or other markers are not recommended'''
*# '''<span style="color:#ff0000">Imaging: upper tract imaging (intermediate, high-risk, and if family history of RCC or other genetic renal tumor syndrome)</span>'''
*#* '''<span style="color:#ff0000">US for intermediate-risk</span>'''
*#** '''<span style="color:#ff0000">Optional for low-risk</span>'''
*#* '''<span style="color:#ff0000">CT urography for high-risk</span>'''
*# '''<span style="color:#ff0000">Cystoscopy (intermediate and high-risk)</span>'''
*#* '''<span style="color:#ff0000">Optional for low-risk</span>'''
**'''<span style="color:#ff0000">Low-risk patients who initially elected not to undergo cystoscopy or upper tract imaging should undergo repeat UA within 6 months'''

=== History and Physical Exam ===

==== History ====
* '''<span style="color:#ff0000">Signs and Symptom'''
**'''Degree of hematuria'''
** '''Persistence of hematuria'''
** '''History of gross hematuria'''
** '''Irritative lower urinary tract symptoms'''
*'''<span style="color:#ff0000">Risk factors for malignancy (8):'''
*# '''<span style="color:#ff0000">Age'''
*# '''<span style="color:#ff0000">Male sex'''
*# '''<span style="color:#ff0000">Smoking'''
*# '''<span style="color:#ff0000">Prior pelvic radiation therapy'''
*# '''<span style="color:#ff0000">Prior cyclophosphamide/ifosfamide chemotherapy'''
*# '''<span style="color:#ff0000">Family history of urothelial cancer or Lynch Syndrome'''
*# '''<span style="color:#ff0000">Occupational exposures to benzene chemicals or aromatic amines (e.g., rubber, petrochemicals, dyes)'''
*# '''<span style="color:#ff0000">Chronic indwelling foreign body in the urinary tract'''
* '''<span style="color:#ff0000">Other causes of microscopic hematuria'''
**'''<span style="color:#ff0000">Medical renal disease'''
*** '''Proteinuria, dysmorphic RBCs, cellular casts, or renal insufficiency on urine microscopy may be associated with medical renal disease, which can cause hematuria'''
**** '''If medical renal disease is suspected, refer patients for nephrologic evaluation. However, risk-based urologic evaluation should still be performed.'''
** '''<span style="color:#ff0000">Gynecologic and non-malignant genitourinary causes of MH'''
*** '''Repeat urinalysis following resolution of the gynecologic or non-malignant genitourinary cause.'''
**** '''<span style="color:#ff0000">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):'''
****# Enlarged prostates and friable surface vessels
****# Randall’s plaques and non-obstructing stones
****# Women with pelvic organ prolapse or vaginal atrophy
***** 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.
** '''MH in patients who are taking anti-coagulants requires the same evaluation evaluation regardless of the type or level of anti-coagulation therapy'''

==== Physical Examination ====
* '''<span style="color:#ff0000">General'''
**'''<span style="color:#ff0000">Blood pressure measurement'''
* '''<span style="color:#ff0000">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 ===
* '''Serum creatinine and GFR (NOT required in CUA guidelines)'''
** Goals of renal function assessment in MH patients (2):
**# 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
**# 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.
* '''Urinary markers'''
** '''Urine cytology and urine markers (NMP22, BTA-stat, and UroVysion FISH) are NOT recommended as a part of the routine MH evaluation (CUA Guidelines recommend cytology)'''
** '''Urine cytology may be useful in patients with persistent MH following a negative work up or those with other risk factors for carcinoma in situ'''

=== Imaging ===
* Goals of upper tract imaging in MH patients (2):
*# Identify malignancies of the renal parenchyma and upper tract urothelium
*# Identify actionable non-malignant diagnoses of the kidney, collecting system, and ureters (e.g. stones)
* CT urography
** Advantages
**# Excellent delineation of the excretory urinary tract
**# Very sensitive for urinary stones
**# Readily identifies renal cortical lesions
**# Provides extra-urinary information as well
** Disadvantages
**# Generally more expensive than renal US
**# Involves ionizing radiation and intravenous contrast
* Renal US
** Advantages
**# Relatively less expensive
**# Does not involve ionizing radiation
**# Reasonable discrimination for cortical lesions
** Disadvantages
**# Image quality is dependent on the operator and the patient’s body habitus
**# Lower sensitivity for urothelial lesions''',''' small solid renal lesions, and kidney stones
* '''Recommended modality based on risk-stratification: (CUA Guidelines recommend US)'''
** '''US for intermediate-risk'''
** '''CT urography for high-risk'''
*** Contraindications to contrast-enhanced CT
**** Chronic kidney disease
**** Allergy to iodine-based contrast
*** If CT contraindicated, consider MR urography; if both CT and MR urography contraindicated, consider retrograde pyelography with non-contrast axial imaging or US
* '''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 or a known genetic renal tumor 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 ===
* '''Recommended for intermediate- and high-risk (CUA Guidelines say >40)'''
* White light cystoscopy (WLC) remains the standard for evaluation of MH
* The benefit of blue light cystoscpy in the evaluation of MH remains unknown

=== Low-risk ===
* The likelihood of upper tract malignancy is exceedingly low
* '''<span style="color:#ff0000">Options (2)'''
** '''<span style="color:#ff0000">Cystoscopy and imaging with renal ultrasound'''
** '''<span style="color:#ff0000">Repeat UA (should be performed within 6 months in order to limit the delay in diagnosis of curable malignancy should an underlying cancer be present)'''
* '''<span style="color:#ff0000">Low-risk patients who initially elected not to undergo cystoscopy or upper tract imaging and who are found to have microhematuria on repeat urine testing should be reclassified as intermediate- or high-risk.'''
** '''In such patients, clinicians should perform cystoscopy and upper tract imaging in accordance with recommendations for these risk strata.'''
** In one large study, patients who had persistent MH on repeat urine testing had a higher rate of malignancy on subsequent evaluation as compared with those who had negative repeat urine testing

== Negative evaluation ==

* '''<span style="color:#ff0000">In patients with a negative hematuria evaluation, obtain a repeat urinalysis within 12 months.</span>'''
** '''Patients with a negative follow-up UA may be discharged from further hematuria evaluation given the very low risk of malignancy'''
** '''For patients with a prior negative hematuria evaluation who have persistent or recurrent microhematuria at the time of repeat urinalysis, engage in shared decision-making regarding need for additional evaluation.'''
* '''For patients with a prior negative hematuria evaluation who develop gross hematuria, significant increase in degree of microhematuria, or new urologic symptoms, clinicians should initiate further evaluation'''

== References ==

* [https://pubmed.ncbi.nlm.nih.gov/32698717/ Barocas, Daniel A., et al.] "Microhematuria: Aua/sufu guideline." ''The Journal of urology'' 204.4 (2020): 778-786.