Microscopic Hematuria

Committee Opinion 703 serves for additional reading today!

Defining Microscopic Hematuria

• 2012 American Urologic Association (AUA) criteria - 3+ RBC/high power field

• The AUA guidelines also noted that if found, recommendation for evaluation for all patients older than age 35 years

  • This evaluation includes cystoscopy and upper urinary tract imaging with CT, with the primary concern being urothelial malignancy

• The data supporting this approach was largely based on male patients - so ACOG and AUGS put together this series of recommendations thinking about the female patient 

  • As an example of how this can be so different: the CO points to a large study where 20% of urinalyses performed had microscopic hematuria, and other studies pointing to incidences between 2% and 31% – that would be a lot of studies!

• These studies do carry risks – radiation and malignancy risk, particularly for young patients.

Differential Diagnosis and Risk Factors

• ACOG points to specimen collection being potentially more challenging in women:

  • Hematuria might result from true hematuria, but also from

    • Menstruation

    • Urogenital tract atrophy

    • Pelvic organ prolapse

    • Other non-threatening urogenital diagnosis (prostatic hypertrophy in men, urethral stricture, etc). – these are much less common in women as well.

  • The primary concern with microscopic hematuria: urothelial malignancy.

    • Risk factors:

      • Male sex

      • Age over 50

      • Previous or current smoker

      • Gross hematuria

      • HIstory of pelvic radiation

    • Male sex specifically has 3.3x more new cases of bladder cancer than female sex

      • 4th most common cancer in men, while not in the top 10 cancers for women

    • Renal cancer is also 1.7x more likely in men.

When is reasonable to consider screening in women?

• Studies looking at women have found:

  • Urologic malignancy rate in women under 40 years with any microscopic hematuria was 0.02%, and older than 40 years was 0.4%

  • Urologic malignancy rate is higher in women with 25 RBCs / hpf or greater

  • Smoking also increases risk.

• Bottom line: women older than 60, with gross hematuria, and history of smoking have highest risk of urologic cancer.

  • Low risk, never smoking women, younger than 50 and fewer than 25 RBC/hpf - risk of urologic malignancy is less than 0.5%. 

• In 2020, the AUA updated their guidelines to incorporate these gender-specific screening pathways, which are helpful to recognize and be  aware of:

  • Low risk women can undergo repeat urinalysis within 6 months, or cystoscopy/renal ultrasound

  • Intermediate risk women should undergo cystoscopy and renal ultrasound

  • High risk should undergo cystoscopy and CT urogram

• Of course, keep your local urogyn / urologist aware of any patient for whom you have concern based on risk factors to discuss evaluation for urothelial cancers.

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AUA/SUFU 2020 Microhematuria Algorithm

Bacteruria, UTI, and Pyelonephritis

Today, we’re going to review all the iterations of urine culture abnormalities in pregnancy. We screen urine cultures in the first trimester and many times again later on in pregnancy, and urinary symptoms are a common complaint.

Asymptomatic bacteriuria is when high levels of bacteria are in urine without associated symptoms. This occurs in 2-7% of pregnant women and typically occurs early in pregnancy.

Urinary tract infections can be broken down into two sub-categories:

1. Lower UTI, or acute cystitis is basically an infection of the bladder, with symptoms of dysuria, urinary frequency, and urgency. They occur in 1-2% of pregnant women.

2. Upper UTI, or acute pyelonephritis may have symptoms of simple cystitis, but include systemic symptoms of infection: flank pain, fevers, chills, nausea/vomiting and costovertebral angle (CVA) tenderness. They occur in 0.5-2% of pregnant women, and more commonly in the 2nd and 3rd trimesters.

Non pregnant women can experience asymptomatic bacteriuria as well as pregnant women. In the non pregnant patient, ASB can be quite prevalent, particularly as we age — over 20% in patients >80 years old. Multiple studies have shown that treatment of asymptomatic bacteriuria in the general, nonpregnant population does not reduce frequency of symptomatic infection or prevent adverse outcomes. Importantly, adhering to this principle helps with antibiotic stewardship.

Pregnant women, however, are different story. As many as 20-35% of pregnant women with asymptomatic bacteriuria will develop symptomatic cystitis or pyelonephritis if untreated, and risk is reduced by 70-80% with treatment. Asymptomatic bacteriuria is not only associated with pyelo, but also associated with adverse pregnancy outcomes, like preterm birth and low birth weight infants. Thus, versus other populations, ASB treatment is imperative in pregnancy.

The most common organisms implicated in these urinary infections include: 

• E. coli - about 70% 

• Klebsiella  - about 3% 

• Enterobacter - about 2% 

• Gram positive organisms (like GBS) = 10% 

Diagnosis and Screening Recommendations for ASB, Cystitis, and Pyelonephritis:

• Asymptomatic bacteriuria 

  1. Finding high-level bacterial growth on urine culture without symptoms consistent with a UTI.

  2. Recommendation per Infectious Disease Society of America to screen all pregnant women for asymptomatic bacteriuria at least once in early pregnancy (usually 12-16 weeks).

  3. Diagnostic criteria:

     1. Isolation of same bacterial strain greater than or equal to 10^5 colony-forming units/mL in two consecutive voided urine samples, or

     2. A single catheterized specimen with one bacterial species isolated in >/= 10^2 cfu/mL 

• Acute Cystitis 

  1. Symptoms as described above (dysuria, etc) with pyuria seen on urinalysis.

  2. Should be confirmed with urine culture, but with typical symptoms and pyuria, should start treating without the culture coming back.

  3. Cystitis should NOT involve systemic symptoms.

• Pyelonephritis 

  1. Can have all of the above (though dysuria may not always be present).

  2. Fevers, chills, flank pain, nausea/vomiting, CVA tenderness.

  3. Pregnant women can become VERY sick 

     1. Estimated that as many as 20% of pregnant women with pyelonephritis develop complications like septic shock syndrome or variants like ARDS.

     2. One study of 32,282 pregnant women in the general obstetric population with pyelo → 23% had anemia, 17% had bacteremia, 7% had respiratory insufficiency, and 2% had renal dysfunction.

  4. Diagnostic evaluation can include:

     1. Urinalysis, urine culture.

     2. CBC

     3. Possibly blood cultures and lactic acid if patient presents with sepsis.

     4. Imaging not routine, but in patients who are severely ill or who have symptoms of renal colic, diabetes, prior urologic surgery, immunosuppression, urosepsis, or repeated pyelo, imaging can help identify other complicating factors, ie. infected stone, renal abscess.

     5. Can consider CT, but ultrasound preferred due to decreased radiation exposure in pregnant women.

Treatment 

• Asymptomatic bacteriuria 

  1. Basic principle is to treat with antibiotics tailored to culture results and then follow up cultures to confirm sterilization of the urine.

  2. Possible antibiotics to consider include beta-lactams, nitrofurantoin, or fosfomycin.

  1. A short course is usually effective in eradicating asymptomatic bacteriuria,  although a single-dose regimens may not be as effective as slightly longer regimens. However, optimal duration of therapy is uncertain.

     1. The only exception is fosfomycin - a single dose can successfully treat bacteriuria.

  1. Follow up 

     1. Up to 30% of women fail to clear asymptomatic bacteriuria after short course therapy, so repeat culture is recommended about a week after finishing antibiotics.

     2. However, there isn’t a lot of data about if we should repeat another culture later on for repeat screening after treatment, or if this is even necessary.

     3. Similarly, not a lot of data about treating again if repeat culture is positive and for how long, though general consensus is to treat.

• Acute cystitis 

  1. Treatment is usually empiric because it’s hard to make someone wait until cultures are back.

  2. Same antibiotic treatment options as for asymptomatic bacteriuria.

  3. Again, treatment time is uncertain, but usually 3-7 day course as long as there are no symptoms/signs of pyelo (except fosfomycin, which is single-dose regimen).

  4. Follow-up repeat culture 7 days after antibiotic completion, as with ASB.

  5. If a woman has 2 or more episodes of recurrent cystitis in pregnancy, it is reasonable to start antibiotic prophylaxis:

     1. Cephalexin 250-500mg qHS or nitrofurantoin 50-100mg qHS depending on susceptibility of organisms on previous cultures.

• Pyelonephritis 

  1. Pregnant people need to be admitted because they are WAY more likely to get super sick compared to nonpregnant women.

  2. Parenteral antibiotics initially, then converted to oral antibiotics when woman has been afebrile for 24-48 hours.

  3. Empiric antibiotics:

     1. Broad spectrum beta-lactams - ie. ceftriaxone 

     2. If someone has ESBL (extended spectrum beta-lactamase) bacteria, can consider a carbapenem.

     3. Avoid fluoroquinolones and aminoglycosides in pregnancy.

  4. Oral antibiotics:

     1. Should usually be beta-lactams, or if second trimester, can consider trimethoprim-sulfamethoxazole (Bactrim).

     2. Do not use nitrofurantoin or fosfomycin because they do not achieve adequate levels in the kidney.

  5. Suppression/Prophylaxis:

     1. Should consider preventative therapy for the duration of pregnancy because recurrent pyelo during pregnancy occurs in 6-8% of women.

     2. Some practices continue antibiotic prophylaxis for six weeks postpartum, but the data is unclear to the benefit of this.