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UPDATE

EVALUATION OF ASYMPTOMATIC MICROSCOPIC


HEMATURIA IN ADULTS: THE AMERICAN UROLOGICAL
ASSOCIATION BEST PRACTICE POLICY—PART I:
DEFINITION, DETECTION, PREVALENCE, AND ETIOLOGY
GARY D. GROSSFELD, MARK S. LITWIN, J. STUART WOLF, JR, HEDVIG HRICAK,
CATHRYN L. SHULER, DAVID C. AGERTER, AND PETER R. CARROLL

H ematuria can originate from any site along the


urinary tract and, whether gross or micro-
scopic, may be a sign of serious underlying disease,
American Urological Association convened the
Best Practice Policy Panel on Asymptomatic Micro-
scopic Hematuria and charged this panel with for-
including malignancy. Gross hematuria usually mulating best practice recommendations for the
causes alarm with the patient, prompting a rush to detection and evaluation of asymptomatic micro-
seek medical attention. Most physicians agree that hematuria.
the presence of gross hematuria warrants a thor- The panel formulated its policy statements and
ough diagnostic evaluation to determine its cause,1 recommendations by consensus, on the basis of a
and therefore there is little controversy in the liter- review of published reports and the panel mem-
ature with respect to the evaluation of gross hema- bers’ own expert opinions. This best practice pol-
turia. icy document is meant to offer guidance to all
In contrast, published reports regarding the di- health care providers whose adult patients may
agnosis, etiology, and evaluation of asymptomatic have asymptomatic microscopic hematuria. The
microscopic hematuria are rife with controversy. panel’s multispecialty membership included a fam-
Microscopic hematuria is an incidental finding of- ily physician, a nephrologist, and a radiologist, as
ten discovered as part of a routine examination. well as urologists.
Whether physicians should routinely screen for After the panel reached an initial consensus, the
hematuria in asymptomatic patients is a point at manuscript was circulated to 85 peer reviewers
issue. Other issues include what amount of blood representing the following medical specialties:
in the urine constitutes significant hematuria, what family practice, internal medicine, radiology, ne-
proportion of patients with asymptomatic micro- phrology, and urology. Comments were received
scopic hematuria are likely to have clinically sig- from 55 peer reviewers, and the panel made nu-
nificant disease, and whether a full urologic evalu- merous changes to the document to incorporate
ation is justified. To address these issues, the the suggested concepts the panel considered to be
warranted.
From the Department of Urology, University of California School
of Medicine, San Francisco and Program in Urologic Oncology, DETECTION AND DEFINITION
University of California San Francisco/Mount Zion Comprehen- OF ASYMPTOMATIC
sive Care Center, San Francisco, California; Departments of MICROSCOPIC HEMATURIA
Urology and Health Services, University of California, Los Ange-
les, Schools of Medicine and Public Health, Los Angeles, Califor- Red blood cells (RBCs) in the urine are not al-
nia; Department of Surgery (Urology), University of Michigan ways a sign of underlying disease. Previous studies
School of Medicine, Ann Arbor, Michigan; Memorial Sloan-Ket- have reported that between 9% and 18% of appar-
tering Cancer Center, New York, New York; Department of Med-
icine, Division of Nephrology, Oregon Health Sciences Univer- ently normal individuals have some degree of he-
sity, Portland, Oregon; and Department of Family Medicine, maturia.2–7 However, the actual number of eryth-
Mayo Medical School and Mayo Clinic Rochester, Rochester, rocytes that can be excreted under “normal”
Minnesota conditions is difficult to determine. Different
Reprint requests: Gary Grossfeld, M.D., c/o Carol Schwartz, methods used by different investigators to deter-
M.P.H., R.D., Guidelines Manager, American Urological Associ-
ation, 1120 North Charles Street, Baltimore, MD 21201-5559 mine the presence of hematuria, different defini-
Submitted: October 5, 2000, accepted (with revisions): Decem- tions of the “normal” population among studies,
ber 12, 2000 the inability to control for activities before urine

© 2001, ELSEVIER SCIENCE INC. UROLOGY 57: 599 – 603, 2001 • 0090-4295/01/$20.00
ALL RIGHTS RESERVED PII S0090-4295(01)00919-0 599
TABLE I. Reported causes of asymptomatic microscopic hematuria
Significant, Requiring Significant, Requiring
Life-Threatening Treatment Observation Insignificant
Bladder cancer Renal calculus Radiation cystitis Urethrotrigonitis
Renal cell carcinoma Vesicoureteral reflux Bladder diverticulum Renal cyst
Prostate cancer Bacterial cystitis Atrophic kidney Duplicated collecting system
Ureteral transitional cell Bladder calculus Bladder neck contracture Prostatic calculus
carcinoma Ureteropelvic junction Interstitial cystitis Bladder neck polyps
Renal transitional cell obstruction Asymptomatic BPH Urethral polyps
carcinoma Renal parenchymal Papillary necrosis Bladder
Metastatic carcinoma disease Renal arteriovenous varices/telangiectasia
Urethral cancer Symptomatic BPH fistula Scarred kidney
Penile cancer Urethral Renal contusion Trabeculated bladder
Renal lymphoma stricture/meatal Polycystic kidney Urethral caruncle
Abdominal aortic aneurysm stenosis Prostatitis Pseudomembranous
Bladder papilloma Cystocele trigonitis
Mycobacterial cystitis Neurogenic bladder Urethritis
Pyelonephritis Cystitis cystica/glandularis Pelvic kidney
Hydronephrosis Ureterocele Caliceal diverticulum
Ureteral calculus Eosinophilic cystitis Exercise hematuria
Renal artery stenosis Phimosis
Renal parenchymal
disease
Renal vein thrombosis
KEY: BPH ⫽ benign prostatic hyperplasia.

collection that may transiently induce hematuria 100%. However, the specificity of urinary dipsticks
(such as exercise, trauma, and/or sexual activity), is limited, ranging from 65% to 99% for 2 to 5 RBCs
and inadequate follow-up of the normal popula- per high-power microscopic field (HPF).8,10 –12
tion under study are all factors that contribute to False-positive results on dipstick analysis may be
this uncertainty.8,9 due to myoglobin or free hemoglobin in the urine,
The degree of hematuria can be measured quan- as well as oxidizing contaminants in the urine such
titatively by determining the number of RBCs per as Betadine (povidone-iodine).9 It should be noted
milliliter of urine excreted (the so-called chamber that in patients with a low urine specific gravity
count), by direct examination of the centrifuged (less than 1.007), most urinary RBCs will lyse and,
urinary sediment (sediment count), or indirectly in this circumstance, urinary dipsticks may be a
by dipstick examination of the urine. The chamber more accurate reflection of hematuria than micro-
count has been suggested to have greater precision scopic examination of the urinary sediment.13
and sensitivity than the sediment count, but the It is recommended that urinalysis to detect mi-
sediment count is easier to perform, less time-con- croscopic hematuria be performed on a freshly
suming, and more cost-effective than the chamber voided, clean-catch, midstream urine specimen.
count.10 Consequently, most investigators prefer The initial determination regarding the presence of
to examine the urinary sediment when evaluating a microscopic hematuria should be based on micro-
patient for the presence of microscopic hematuria. scopic examination of the urinary sediment.
The chamber count and sediment count have been The standard technique involves centrifugation
shown to correlate with acceptable sensitivity.10 of 10 mL of urine for 5 minutes at approximately
However, the sediment count is only a semiquan- 2000 rpm.14 After centrifugation, the supernatant
titative method of determining the degree of hema- should be discarded and the sediment resuspended
turia, and thus not entirely interchangeable with in 0.5 to 1.0 mL of the remaining urine. A drop of
the chamber count.8,9 resuspended urine should be examined under the
The simplest way to detect microscopic hematu- high-power microscope objective. If urine contam-
ria is with a urinary dipstick. Hemoglobin, either ination by the skin or vaginal mucosa is evident,
free in the urine or within urinary RBCs, catalyzes such as the presence of squamous epithelial cells,
an oxidation reaction between substances on the the examination should be repeated on a new spec-
dipstick, resulting in a color change that indicates imen and consideration given to obtaining a cath-
the presence of hematuria.9 Urinary dipsticks have eterized specimen.
been very useful in the detection of asymptomatic The most commonly accepted upper limit of nor-
microscopic hematuria, with a sensitivity of 91% to mal for urinary RBCs, based on examination of the

600 UROLOGY 57 (4), 2001


TABLE II. Incidence of highly or moderately significant disease in patients with hematuria who
underwent full urologic evaluation
Patients
with Highly
or Patients
Moderately with
Significant Urologic
Patients Disease Malignancy
Reference (n) Population Evaluated (%) (%)
Bard22 177 Women ⱖ20 yr 3.4 0
Britton et al.17 61 Men 60–85 yr 56 8.2
Britton et al.18 319 Men ⬎60 yr NA 8.3
Carson et al.23 200 All patients referred for urologic 52 13
evaluation
Davides et al.24 150 All patients referred for urologic 49 8.7
evaluation
Fracchia et al.25 100 All patients referred for urologic 13 5
evaluation
Greene et al.26 500 All patients referred for urologic 9.4 2.2
evaluation
Golin and Howard27 246 All patients referred for urologic 22 10
evaluation
Jones et al.28 100 Men ⬍40 yr 18 0
Mariani et al.5 1000 All patients referred for urologic 32 8.6
evaluation
Messing et al.12 19 Men ⱖ50 yr 53 26
Messing et al.16 31 Men ⱖ50 yr 48 25.8
Messing et al.19 192 Men ⱖ50 yr 33 8.3
Murakami et al.29* 1034 All patients with microhematuria 22 2.3
on annual health examination
Ritchie et al.20* 76 Patients with microhematuria 17 2.6
on health screening who
underwent subsequent
evaluation
Thompson21* 85 Men ⱖ40 yr 22 1.2
* Patients in these three studies were not from selected populations. Asymptomatic microhematuria was an incidental discovery during routine physical examination. Patients
in all the other studies were either urologic referral patients or from selected screening populations.
KEY: NA ⫽ not available.

urine sediment, is 2 to 3 RBCs/HPF.8,15 Although maturia is 3 or more RBCs/HPF on microscopic


many investigators have used this definition to de- evaluation of the urinary sediment from two of
fine the presence of microscopic hematuria, other three properly collected urinalysis specimens. As
investigators have considered more than 5 RBCs/ there is no safe lower limit for hematuria, risk fac-
HPF to be evidence of significant microscopic he- tors for significant disease should be taken into
maturia. Still others have considered any degree of consideration before deciding to defer an evalua-
hematuria to be abnormal. tion in patients with 1 or 2 RBCs/HPF. High-risk
It has been documented that hematuria associ- patients (especially those with a history of smoking
ated with significant urologic disease may be inter- or chemical exposure) should be considered for a
mittent in nature.16 Thus, a negative repeated uri- full urologic evaluation after one properly per-
nalysis in someone who has previously had a formed urinalysis documenting the presence of at
positive test may not be sufficient to exclude the least 3 RBCs/HPF.
presence of significant disease. To account for the Given the limited specificity of urinary dipsticks
intermittent nature of hematuria due to urologic and the risk and expense of a hematuria evaluation,
malignancy, Mariani and colleagues5 proposed an initial finding of microscopic hematuria on uri-
that patients with more than 3 RBCs/HPF on two of nary dipstick should be confirmed by microscopic
three properly collected and examined urine spec- evaluation of the urinary sediment. A positive dip-
imens should be considered to have microhematu- stick examination that is not confirmed with exam-
ria and thus evaluated appropriately. ination of the urinary sediment should not lead to
The recommended definition of microscopic he- a complete urologic evaluation.

UROLOGY 57 (4), 2001 601


PREVALENCE OF ASYMPTOMATIC pational toxins such as dyes, benzenes, and aro-
MICROSCOPIC HEMATURIA matic amines.
The prevalence of asymptomatic microscopic he-
maturia has been estimated in both unselected, ETIOLOGY
population-based studies and in screening or refer-
ral-based studies examining selected patient popu- The proportion of patients with asymptomatic
lations. Woolhandler and colleagues11 reviewed microscopic hematuria who are subsequently diag-
five population-based cohort studies with patient nosed with significant urologic disease reflects
populations ranging from 1000 to 95,200. The es- both the patient population under investigation
timated prevalence of asymptomatic microscopic and the extent of the urologic evaluation that is
hematuria varied in these studies from 0.19% to performed. Most studies in which patients with
16.1%. Such wide variations reflect the differences asymptomatic microscopic hematuria have under-
in the age and sex of populations screened, the gone full urologic evaluation have included refer-
amount of follow-up, and the number of screening ral-based populations. A full evaluation in these
studies per patient. studies often included a repeated urinalysis, urine
The prevalence of microscopic hematuria has culture, upper urinary tract imaging, cystoscopy,
also been determined in patient populations se- and urinary cytology. Of the patients who undergo
lected for their participation in health care screen- a full urologic evaluation, a cause for asymptom-
ing programs and is reported to range from 2.5% to atic microscopic hematuria can be determined in
21.1%.12,16 –21 In two studies of men older than 60 32% to 100%.5,12,16 –29 Finding the cause is depen-
years who underwent voluntary screening for blad- dent on both the population studied and the will-
der cancer, Britton and colleagues17,18 reported ingness of the investigator to assign “insignificant”
prevalences of 13% and 20.1%. In three studies by findings as the cause of the hematuria.
Messing and colleagues,12,16,19 high-risk, asymp- Causes of asymptomatic microscopic hematuria
tomatic men older than 50 years were screened for range from minor, incidental findings that do not
require treatment to highly significant lesions that
bladder cancer using urinary dipsticks to detect
immediately threaten the patient’s life. The tradi-
occult bleeding. Microscopic hematuria was
tional classification of such causes was based on
present in 10% to 21% of these subjects.
three categories as proposed by Greene and col-
There is no general consensus regarding when to
leagues.26 Highly significant disease posed a clear
test for microscopic hematuria in asymptomatic
threat to the patient’s life and/or required major
adults in a primary care setting. Although bladder surgery. Moderately significant disease was consid-
cancer is the most commonly detected malignancy ered to be remotely life-threatening and usually
in patients with microscopic hematuria, no major required some form of medical treatment. Insignif-
organization currently recommends screening for icant disease did not require treatment. More re-
bladder cancer in asymptomatic adults. The Amer- cently, Mariani and colleagues5 revised this classi-
ican Cancer Society has not issued any specific fication into four categories (Table I). Although
guidelines on screening for bladder cancer, and the these categories are inherently subjective, a num-
U.S. Preventive Services Task Force (1996) and the ber of investigators continue to find them useful.
Canadian Task Force on the Periodic Health Ex- Table II summarizes the incidence of moderately
amination both recommend against routinely and highly significant urologic disease in patients
screening asymptomatic patients for hematuria to with asymptomatic microscopic hematuria who
identify those with urologic malignancies. The Ca- underwent a full urologic evaluation. The percent-
nadian Task Force has also concluded that the ev- age differences from study to study mainly reflect
idence is insufficient to recommend either for or differences in the patient populations under inves-
against such screening even in specific high-risk tigation.
patients. Patients with asymptomatic microscopic hema-
As no agreement has been reached on when to turia who are at risk of urologic disease or primary
test for asymptomatic microscopic hematuria in renal disease should undergo an appropriate eval-
the primary care setting, the physician should be uation because (a) such an evaluation will often
guided by the results of the patient’s history and determine the cause of the hematuria and (b) a
physical examination in deciding whether testing substantial number of patients will be found to
is appropriate. Risk factors for significant underly- have moderately or highly significant disease (in-
ing disease include age older than 40 years; tobacco cluding malignancy). For patients at low risk of
use; analgesic abuse (eg, phenacetin); laxatives disease, some components of the evaluation may
that may cause renal disease; history of pelvic irra- be deferred (see Part II of the Best Practice Policy in
diation; cyclophosphamide; and exposure to occu- this issue of UROLOGY).

602 UROLOGY 57 (4), 2001


ACKNOWLEDGMENT. To Lisa Cowen, Ph.D. and Carol plasia in patients with asymptomatic microscopic hematuria: a
Schwartz, M.P.H. decision analysis. J Urol 139: 1002–1006, 1988.
15. Copley JB: Isolated asymptomatic hematuria in the
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The Asymptomatic Microscopic Hematuria in Adults Best Practice Policy has been published in summary
format in American Family Physician, Volume 63, March 15, 2001.

UROLOGY 57 (4), 2001 603

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