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Assessment of Asymptomatic Microscopic Hematuria in Adults VICTORIA J Assessment of Asymptomatic Microscopic Hematuria in Adults VICTORIA J. SHARP, MD, MBA; KERRI T. BARNES, MD, MPH; and BRADLEY A. ERICKSON, MD, MS University of Iowa Hospitals and Clinics, Iowa City, Iowa Although routine screening for bladder cancer is not recommended, microscopic hematuria is often incidentally dis- covered by primary care physicians. The American Urological Association has published an updated guideline for the management of asymptomatic microscopic hematuria, which is defined as the presence of three or more red blood cells per high-power field visible in a properly collected urine specimen without evidence of infection. The most com- mon causes of microscopic hematuria are urinary tract infection, benign prostatic hyperplasia, and urinary calculi. However, up to 5% of patients with asymptomatic microscopic hematuria are found to have a urinary tract malig- nancy. The risk of urologic malignancy is increased in men, persons older than 35 years, and persons with a history of smoking. Microscopic hematuria in the setting of urinary tract infection should resolve after appropriate antibiotic treatment; persistence of hematuria warrants a diagnostic workup. Dysmorphic red blood cells, cellular casts, protein- uria, elevated creatinine levels, or hypertension in the presence of microscopic hematuria should prompt concurrent nephrologic and urologic referral. The upper urinary tract is best evaluated with multiphasic computed tomography urography, which identifies hydronephrosis, urinary calculi, and renal and ureteral lesions. The lower urinary tract is best evaluated with cystoscopy for urethral stricture disease, benign prostatic hyperplasia, and bladder masses. Voided urine cytology is no longer recommended as part of the routine evaluation of asymptomatic microscopic hematuria, unless there are risk factors for malignancy. (Am Fam Physician. 2013;88(11):747-754. Copyright © 2013 American Academy of Family Physicians.) Author disclosure: No rel- n its 2011 recommendation statement, hematuria and in up to 30% to 40% of evant financial affiliations. the U.S. Preventive Services Task Force patients with gross hematuria.8 Studies CME This clinical content did not find sufficient evidence for or have revealed that recommended diagnostic conforms to AAFP criteria against screening for bladder cancer in guidelines are rarely followed, resulting in for continuing medical I asymptomatic adults.1 Despite this, micro- inappropriate and costly referrals, and fail- education (CME). See CME Quiz Questions on page scopic hematuria is often found inciden- ure to detect many treatable causes of hema- 732. tally during routine health screenings, with turia.7-9 Although the reasons for this lack of ▲ 2-6 Patient information: a prevalence of about 2% to 31%. Because adherence to guideline recommendations A handout on this topic primary care physicians commonly are the are unclear, they are likely secondary to a is available at http:// first to recognize asymptomatic microscopic combination of factors, including confusion familydoctor.org/family hematuria, an evidence-based approach to about suggested workup, the rarity of find- doctor/en/diseases- conditions/microscopic- the evaluation of hematuria is necessary. ing clinically significant etiologies, patient hematuria.html. In 2012, the American Urological Associa- compliance with follow-up, and costs.7,10,11 tion (AUA) published an updated guideline An algorithmic approach to the diagnosis on the diagnosis, evaluation, and follow-up and management of asymptomatic micro- of asymptomatic microscopic hematuria in scopic hematuria is provided in Figure 1.6,12-14 adults.6 Based on the guideline, this article describes the current approaches to diagno- Etiology sis, follow-up, and referral for patients with Hundreds of diseases have been shown to asymptomatic microscopic hematuria. cause hematuria. In the small percentage of In many patients with microscopic hema- patients for whom an etiology is identified, turia, a specific cause or pathology is not causes may include urinary tract infection, found.7 Nevertheless, formal evaluation is benign prostatic hyperplasia, medical renal critical, because malignancies are detected disease, urinary calculi, urethral stricture in up to 5% of patients with microscopic disease, and urologic malignancy.6-8,15 Table 1 DownloadedDecember 1,from 2013 the ◆American Volume Family 88, Number Physician 11website at www.aafp.org/afp.www.aafp.org/afp Copyright © 2013 American Academy of FamilyAmerican Physicians. Family For the Physicianprivate, non -747 commercial use of one individual user of the website. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. Microscopic Hematuria Diagnosis and Management of Incidentally Discovered Microscopic Hematuria Dipstick testing positive for blood A Assess for: Risk factors for malignancy (Table 2) Contraindications to radiation Microscopic urinalysis Contrast media allergies Renal insufficiency Less than three red blood cells per high-power field Low risk of malignancy High risk of malignancy or and/or Repeat urinalysis three Renal insufficiency Good renal function times at six-week intervals Radiation sensitivity No contrast media allergy Contrast media allergy No contraindications to radiation Negative Positive Less optimal imaging option (e.g., magnetic Computed tomography No additional Three or more red blood resonance urography, renal ultrasonography, urography and workup cells per high-power field noncontrast computed tomography, urologic referral magnetic resonance imaging, retrograde pyelography) and urologic referral Assess for urinary tract infection and other benign causes (e.g., vigorous exercise, menstruation, recent urologic procedure) Repeat urinalysis six weeks after treatment or discontinuation of contributing factor Cystoscopy Negative Positive Negative Positive No additional workup Renal function testing to assess Annual urinalysis for two years Treat for medical renal disease (e.g., dysmorphic red blood cells, cellular casts, proteinuria) Negative Positive Release from care Annual repeat urinalysis positive; repeat anatomic evaluation Negative Positive within three to five years Go to A Concurrent nephrologic referral Figure 1. Algorithm for the diagnosis and management of incidentally discovered microscopic hematuria. Adapted with permission from Davis R, Jones JS, Barocas DA, et al. Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline. American Urological Association Education and Research, Inc., 2012:1-30, with additional information from references 12 through 14. lists the most common etiologies after ini- minute for 10 minutes (the number of revo- tial evaluation of microscopic hematuria.2,7-9 lutions and minutes may vary, depending The risk of urologic malignancy increases on the centrifuge). The supernatant should significantly in men, persons older than be discarded and the sediment suspended 35 years, and persons with a history of smok- in 0.3 mL of supernatant and/or saline, and ing.1,6 Table 2 lists other factors that have placed on a microscopic slide. At least 10 to been shown to increase the risk of urologic 20 microscopic fields should be examined malignancy in patients with asymptomatic under 400× magnification.16 According to the microscopic hematuria.6 AUA, the presence of three or more red blood cells on a single, properly collected, noncon- Clinical Relevance taminated urinalysis without evidence of CONFIRMATION OF HEMATURIA infection is considered clinically significant The most important test in the evaluation microscopic hematuria.6 If the specimen of hematuria is a microscopic examination shows large amounts of squamous epithelial of the urine.6 Approximately 10 mL of mid- cells (more than five per high-power field) or stream urine should be collected and imme- if the patient is unable to provide an uncon- diately centrifuged at 2,000 revolutions per taminated specimen secondary to anatomic 748 American Family Physician www.aafp.org/afp Volume 88, Number 11 ◆ December 1, 2013 Microscopic Hematuria Table 1. Common Etiologies of Microscopic Hematuria Diagnosis Frequency (%) the presence of hemoglobinuria, myoglo- Unknown 43 to 68 binuria, semen, highly alkaline urine (pH Urinary tract infection 4 to 22 greater than 9), and concentrated urine.12,19 Benign prostatic hyperplasia 10 to 13 Ascorbic acid (vitamin C) has been shown Urinary calculi 4 to 5 to cause false-negative results on dipstick Bladder cancer 2 to 4 testing because of its reducing properties; Renal cystic disease 2 to 3 therefore, patients taking vitamin C supple- Renal disease 2 to 3 ments and undergoing urinary evaluation Kidney cancer < 1 may benefit from up-front microscopic Prostate cancer < 1 examination.20 Urethral stricture disease < 1 POSITIVE DIPSTICK TEST Information from references 2, and 7 through 9. AND NEGATIVE MICROSCOPIC RESULTS Patients who screen positive for hematuria with a urine dipstick test but have a negative Table 2. Common Risk Factors for follow-up microscopic examination should Urinary Tract Malignancy in Patients undergo three additional microscopic tests with Microscopic Hematuria to rule out hematuria. If one of these repeat test results is positive on microscopic analy- Age older than 35 years sis, the patient is considered to have micro- Analgesic abuse scopic hematuria. If all three specimens are Exposure to chemicals or dyes (benzenes or negative on microscopy, the patient
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