Asymptomatic Microscopic Hematuria in Adults: Summary of the AUA Best Practice Policy Recommendations GARY D. GROSSFELD, M.D., University of California, San Francisco, School of Medicine, San Francisco, California J. STUART WOLF, JR., M.D., University of Michigan Medical School, Ann Arbor, Michigan MARK S. LITWIN, M.D., M.P.H., University of California, Los Angeles, Schools of Medicine and Public Health, Los Angeles, California HEDVIG HRICAK, M.D., PH.D., Memorial Sloan-Kettering Cancer Center, New York, New York CATHRYN L. SHULER, M.D., Kaiser Permanente, Portland, Oregon DAVID C. AGERTER, M.D., Mayo Clinic, Rochester, Minnesota PETER R. CARROLL, M.D., University of California, San Francisco, School of Medicine, San Francisco, California The American Urological Association (AUA) convened the Best Practice Policy Panel on Asympto- matic Microscopic Hematuria to formulate policy statements and recommendations for the evalu- ation of asymptomatic microhematuria in adults. The recommended definition of microscopic hematuria is three or more red blood cells per high-power microscopic field in urinary sediment from two of three properly collected urinalysis specimens. This definition accounts for some degree of hematuria in normal patients, as well as the intermittent nature of hematuria in patients with urologic malignancies. Asymptomatic microscopic hematuria has causes ranging from minor findings that do not require treatment to highly significant, life-threatening lesions. Therefore, the AUA recommends that an appropriate renal or urologic evaluation be performed in all patients with asymptomatic microscopic hematuria who are at risk for urologic disease or primary renal dis- ease. At this time, there is no consensus on when to test for microscopic hematuria in the primary care setting, and screening is not addressed in this report. However, the AUA report suggests that the patient’s history and physical examination should help the physician decide whether testing is appropriate. (Am Fam Physician 2001;63:1145-54.) lood in the urine (hematuria) members’ expert opinions. In addition to urol- can originate from any site along ogists, the multispecialty panel included a fam- the urinary tract and, whether ily physician, a nephrologist and a radiologist. gross or microscopic, may be a Funding in support of panel activities was pro- sign of serious underlying dis- vided by the AUA. A summary of the recom- Bease, including malignancy. The literature mendations is presented in this article; the full agrees that gross hematuria warrants a thor- text will be published in Urology.3,4 ough diagnostic evaluation.1 By contrast, microscopic hematuria is an incidental find- The initial determination of microscopic hema- ing, and whether physicians should test for turia should be based on microscopic examina- hematuria in asymptomatic patients remains tion of urinary sediment from a freshly voided, at issue. No major organization currently rec- clean-catch, midstream urine specimen. ommends screening for microscopic hema- Hematuria can be measured quantitatively turia in asymptomatic adults, even though by any of the following: (1) determination of bladder cancer is the most commonly de- the number of red blood cells per milliliter of tected malignancy in such patients.2 urine excreted (chamber count), (2) direct The American Urological Association (AUA) examination of the centrifuged urinary sedi- convened a Best Practice Policy Panel to for- ment (sediment count) or (3) indirect exami- mulate recommendations for the evaluation of nation of the urine by dipstick (the simplest patients with asymptomatic microhematuria. way to detect microscopic hematuria). Given The panel does not offer recommendations the limited specificity of the dipstick method regarding routine screening for microscopic (65 percent to 99 percent for two to five red hematuria. The recommendations are based on blood cells per high-power microscopic field), extensive review of the literature and the panel however, the initial finding of microscopic MARCH 15, 2001 / VOLUME 63, NUMBER 6 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1145 The recommended definition of microscopic hematuria is TABLE 1 Risk Factors for Significant Disease three or more red blood cells per high-power field on in Patients with Microscopic Hematuria microscopic evaluation of urinary sediment from two of three properly collected urinalysis specimens. Smoking history Occupational exposure to chemicals or dyes (benzenes or aromatic amines) hematuria by the dipstick method should be History of gross hematuria confirmed by microscopic evaluation of uri- Age >40 years History of urologic disorder or disease nary sediment.5-8 History of irritative voiding symptoms The recommended definition of micro- History of urinary tract infection scopic hematuria is three or more red blood Analgesic abuse cells per high-power field on microscopic History of pelvic irradiation evaluation of urinary sediment from two of three properly collected urinalysis specimens. Adapted with permission from Grossfeld GD, Wolf To account for intermittent positive tests for JS, Litwin MS, Hricak H, Shuler CL, Agerter DC, Car- hematuria in patients with urologic malig- roll P. Evaluation of asymptomatic microscopic nancies,6,9 one group of investigators10 pro- hematuria in adults: the American Urological Associ- ation best practice policy recommendations. Part II: posed that patients with more than three red patient evaluation, cytology, voided markers, imag- blood cells per high-power field from two of ing, cystoscopy, nephrology evaluation, and follow- three properly collected urine specimens up. Urology 2001;57(4) (In press). should be considered to have microhematuria and, thus, should be evaluated appropriately. However, before a decision is made to defer evaluation in patients with one or two red Patients with asymptomatic microscopic blood cells per high-power field, risk factors hematuria who are at risk for urologic disease for significant disease should be taken into or primary renal disease should undergo an consideration (Table 1).4 High-risk patients appropriate evaluation. In patients at low risk should be considered for full urologic evalua- for disease, some components of the evaluation tion after one properly performed urinalysis may be deferred. documenting the presence of at least three red Asymptomatic microscopic hematuria has blood cells per high-power field. many causes, ranging from minor incidental findings that do not require treatment to The prevalence of asymptomatic microscopic highly significant lesions that are immediately hematuria varies from 0.19 percent to as high life-threatening. Therefore, hematuria has as 21 percent. been classified into four categories: life- In five population-based studies, the preva- threatening; significant, requiring treatment; lence of asymptomatic microscopic hematuria significant, requiring observation; and varied from 0.19 percent to 16.1 percent.7 Dif- insignificant1,10 (Table 2).1 ferences in the age and sex of the populations Most studies in which patients with asymp- screened, the amount of follow-up and the tomatic microscopic hematuria have under- number of screening studies per patient gone full urologic evaluation (often including account for this range. In older men, who are repeat urinalysis, urine culture, upper urinary at a higher risk for significant urologic disease, tract imaging, cystoscopy and urinary cytol- the prevalence of asymptomatic microscopic ogy) have included referral-based popula- hematuria was as high as 21 percent.6,9,11-13 tions. A cause for asymptomatic microscopic 1146 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 63, NUMBER 6 / MARCH 15, 2001 Hematuria TABLE 2 Reported Causes of Asymptomatic Microscopic Hematuria The rightsholder did not grant rights to reproduce this item in electronic media. For the missing item, see the original print version of this publication. hematuria was determined in 32 percent to tors suggest the presence of renal parenchymal 100 percent of these patients.6,9-23 disease. In the absence of massive bleeding, a An algorithm for the initial evaluation of total protein excretion in excess of 1,000 mg newly diagnosed asymptomatic microscopic per 24 hours would be unlikely and should hematuria is provided in Figure 1.4 An prompt a thorough evaluation or nephrology approach to the urologic evaluation of referral24 (Figure 2).4 patients without conditions suggestive of pri- Red cell casts are virtually pathognomonic mary renal disease is presented in Figure 2.4 for glomerular bleeding. Unfortunately, they are a relatively insensitive marker. Therefore, The presence of significant proteinuria, red cell it is useful to examine the character of the red casts or renal insufficiency, or a predominance of blood cells.25 Dysmorphic urinary red blood dysmorphic red blood cells in the urine should cells show variation in size and shape and prompt an evaluation for renal parenchymal usually have an irregular or distorted outline. disease or referral to a nephrologist. Such red blood cells are generally glomerular Significant proteinuria is defined as a total in origin. In contrast, normal doughnut- protein excretion of greater than 1,000 mg per shaped red blood cells are generally due to 24 hours (1 g per day), or greater than 500 mg lower urinary tract bleeding. Accurate deter- per 24 hours (0.5 g per day) if protein excre- mination of red blood cell morphology may tion is persistent or increasing or if other fac- require