ADULT UROLOGY

A NEW DIAGNOSTIC ALGORITHM FOR THE EVALUATION

OF MICROSCOPIC HEMATURIA
JAMISON S. JAFFE, PHILLIP C. GINSBERG, RAJI GILL, AND RICHARD C. HARKAWAY

ABSTRACT
Objectives. To evaluate a new diagnostic algorithm for microscopic hematuria in which intravenous urog-
raphy (IVU) is performed as a secondary radiographic study when microhematuria has persisted for 3
months after the initial workup with renal ultrasound (US) and cystoscopy was negative.
Methods. We evaluated 372 consecutive patients who presented with microhematuria and negative urine
cultures and cytologic findings at our institution. All patients underwent renal US scanning and cystoscopy
as their initial evaluation. All patients underwent re-evaluation 3 months after the initial workup. Patients
with persistent microhematuria with no apparent etiology were then evaluated with IVU.
Results. The initial evaluation was negative in 212 of 372 patients. Eighty-one of these patients had
persistence of their microhematuria at the 3-month follow-up without a definitive diagnosis. Seventy-five of
these patients underwent IVU. Abnormalities were found in 11 of the 75 patients. Six patients had renal
stones, two had ureteral stones, two had ureteral tumors, and one had a tumor of the renal pelvis. Forty of
the 131 patients with resolution of their microhematuria underwent IVU at their request. All those studies
were normal.
Conclusions. The combination of cystoscopy and renal US along with urinalysis, urine culture, and cytology
is a good initial evaluation in patients with microhematuria. Those patients with persistent microhematuria
after 3 months without definite etiology of the bleeding may still benefit from IVU. UROLOGY 57: 889–894,
2001. © 2001, Elsevier Science Inc.

A symptomatic microhematuria is a common

clinical problem that has a 1% to 13% preva-
lence in adults.1 Multiple etiologies exist for micro-
hematuria, ranging from insignificant lesions to
potentially life-threatening neoplastic lesions.2
Clinical evaluation is mandatory to exclude an un-
derlying genitourinary malignancy.3 The estab-
lished urologic evaluation has undergone little
change during the years and consists of urinalysis
with culture, cytology, cystoscopy, and an upper
tract radiologic study such as intravenous urogra-
phy (IVU).3 With the advent of ultrasound (US)
and axial computed tomography, questions have
been raised regarding the role of these radiologic
modalities in the evaluation of microhematuria.
IVU has historically been the initial radiologic
study for the evaluation of the upper tracts in pa-
From the Division of Urology, Department of Surgery, Albert
Einstein Medical Center, Philadelphia, Pennsylvania
Reprint requests: Richard C. Harkaway, M.D., Albert Einstein
Medical Center, Klein Professional Office Building, Suite 500,
5401 Old York Road, Philadelphia, PA 19141
Submitted: June 14, 2000, accepted (with revisions): December
8, 2000
tients with hematuria. However, the value of IVU
in the evaluation of the upper urinary tract has
been questioned.4 –7 US has proved to be sensitive
in detecting masses, cysts, and hydronephrosis in
the kidney.8 –10 Because US is more sensitive in de-
tecting the more common renal cell carcinoma
(RCC) than in detecting the elusive urothelial tran-
sitional cell carcinoma (TCC) compared with IVU,
we designed a prospective preliminary study to de-
termine whether US can replace IVU in the initial
evaluation of patients who present with asymp-
tomatic microhematuria.11
MATERIAL AND METHODS
We evaluated 400 consecutive patients who presented with
asymptomatic microhematuria between January 1997 and
January 2000. The study was approved by the Human Subject
Review Board, and all subjects who participated in the study
completed an informed consent form that had been explained
to them by an attending urologist. Microhematuria was de-
fined as greater than 2 red blood cells per high power field
(HPF). Urinalysis and urine culture were performed on all
individuals to rule out an infectious etiology for the microhe-
maturia. Microscopic analysis of all urine specimens was done
to correlate the degree of microhematuria with the results of

© 2001, ELSEVIER SCIENCE INC. 0090-4295/01/$20.00

ALL RIGHTS RESERVED PII S0090-4295(00)01124-9 889
 FIGURE 1. Microscopic hematuria algorithm.
the urine dipstick. Urine cytology was performed to evaluate
whether a neoplastic process was the source of the hematuria
before any radiologic or urologic procedures. Renal US and
cystoscopy were then performed on all patients with negative
urinalysis and cytologic findings. All patients underwent re-
evaluation 3 months after the initial evaluation. If the patient
had persistent microhematuria with no definitive diagnosis,
IVU was performed (Fig. 1).
RESULTS
The study group consisted of 372 patients (me-
dian age 58 years, range 26 to 90), 150 men (40%)
and 222 women (60%). Twenty-eight patients
were not enrolled in the study because of positive
urinalysis, culture, or cytologic findings. Two of
these 28 patients had high-grade bladder TCC di-
agnosed by urine cytologic analysis with subse-
890
quent cystoscopy, and the remaining 26 patients
had urinary tract infections diagnosed by urinaly-
sis and culture. Both individuals with bladder tu-
mors were men with positive smoking histories.
The initial evaluation, consisting of cystoscopy and
renal US, resulted in a diagnosis in 160 of the pa-
tients (98 men and 62 women) and was negative in
the remaining 212 patients (52 men and 160 wom-
en). The diagnoses stratified by age and sex and the
risk factors in those individuals can be found in
Tables I and II, respectively.
At the 3-month follow-up evaluation, persistent
microhematuria without a definitive etiology ex-
isted in 81 (38%) of the 212 patients; the hematuria
had resolved in 131 (62%) of the 212 patients (Fig.
2). Of the 81 patients with persistent microhema-
UROLOGY 57 (5), 2001
TABLE I. Diagnosis of the 160 patients whose diagnosis was made using cystoscopy and renal
ultrasound based on age and sex
Age <65 yr Age >65 yr
Men Women Men Women
Diagnosis (n ⴝ 45) (n ⴝ 43) (n ⴝ 53) (n ⴝ 19)
Medullary sponge kidney 3 4 0 0
Calculi (renal/ureteral) 11 15 5 4
Calculi (bladder) 0 0 2 0
Renal tumor 1 2 4 4
Prostatic bleeding (BPH) 16 0 24 0
Bladder cancer 3 0 8 3
Hemorrhagic cystitis 1 3 0 0
Urethral stricture 1 0 3 0
Endometriosis 0 2 0 0
Carcinoma in situ 1 0 3 2
Cystitis/inflammation 8 17 4 6
KEY: BPH ⫽ benign prostatic hyperplasia.

TABLE II. Risk factors of the 160 patients who were found to have a urologic neoplasm using
cystoscopy and renal ultrasound
Men Women
Family Family
Risk Factor None History Smoking Both None History Smoking Both
Renal tumor 1 0 2 2 0 0 4 2
Bladder cancer 1 0 7 3 0 0 2 1
Carcinoma in situ 0 0 3 1 0 0 1 1

turia, 75 underwent IVU, with 6 patients lost to
follow-up. Eleven (14%) of these 75 patients had
abnormal IVU findings. Of the 11 patients, 6 had
renal stones (55%), 2 had ureteral stones (18%)
varying in size from 3 to 9 mm, 2 had ureteral
tumors (18%), and 1 had a tumor of the renal pel-
vis (9%). One of the ureteral tumors was distal,
measuring 1 mm in size; the second ureteral tumor
was in the mid-ureter and measured 1.5 mm. The
tumor in the renal pelvis was 1.8 mm. All tumors
were grade 1/3 TCC. Forty patients with resolution
of the microhematuria underwent IVU at their re-
quest. All 40 patients had negative IVU findings.
COMMENT
The most important reason for evaluating a pa-
tient with hematuria is to exclude a urologic neo-
plasm. IVU has been the preferred study to image
the upper tract for microhematuria; however, cer-
tain limitations exist.4 –7 Ultrasound was found to
be more sensitive in detecting the more common
RCC than in detecting the elusive urothelial tumor
compared with IVU.11 Our findings were similar to
those of Corwin and Silverstein1 who demon-
strated that US could be substituted for IVU in the
initial evaluation of a patient with asymptomatic
microhematuria without compromising the detec-
tion of significant urologic lesions while decreas-
ing the cost and morbidity associated with the ini-
tial urologic evaluation that includes IVU.
However, in an effort to maximize diagnostic sen-
sitivity, Khadra et al.12 reported that the evaluation
of both gross and microhematuria with either US
or IVU alone poses a significant risk of missing
upper tract neoplastic pathologic conditions and
recommended combining the two studies for max-
imal diagnostic efficacy.
In our current study, US missed eight calculi and
three urothelial tumors that were diagnosed with
IVU 3 months after the initial evaluation. The eight
calculi detected were asymptomatic and did not
result in any complications as a result of the
3-month delay between the initial evaluation and
IVU. Six of the eight missed calculi were renal cal-
culi. Even though our results with renal US in de-
tecting renal calculi appear to be poor, it is consis-
tent with the sensitivity of US for detecting renal
calculi, which has been documented in published
reports as 64% to 96%.13,14
All three urothelial tumors were low grade and
did not produce any degree of collecting system
dilation. Whether a 3-month delay in the diagnosis
of these low-grade tumors resulted in a poorer
prognosis for these patients is unclear, but the 3

UROLOGY 57 (5), 2001 891

 FIGURE 2. Study summary diagrams.
patients with urothelial tumors represented a mi-
nority (0.8%) of the total patients in the study.
The cost effectiveness of using US as the initial
study in the evaluation of asymptomatic microhe-
maturia has previously been reported.1,8 Corwin
and Silverstein1 demonstrated that diagnostic ac-
curacy was maintained and the morbidity of the
workup was decreased when US was used instead
of IVU in the initial evaluation of asymptomatic
microhematuria. At our institution, IVU costs
$369.00 and renal US costs $254.25. A total of 372
patients underwent renal US and 75 patients would
have undergone IVU according to our proposed
algorithm. The net savings at our institution in the
evaluation of this group of 372 patients was
$15,012. The formula is as follows: Cost of IVU if
892
done on all study patients ⫺ (Cost of US on all
study patients ⫹ Cost of IVUs performed in the
study) or (372 patients ⫻ $369) ⫺ [(372 ⫻
$254.25) ⫹ (75 ⫻ $369)] ⫽ $15,012. This net
savings of $15,012 does not include the 40 individ-
uals who underwent IVU at their request after neg-
ative US findings and resolution of the microhema-
turia, since these patients would not have
undergone IVU under the proposed algorithm.
Goessl et al.15 demonstrated that abdominal US
combined with a plain abdominal film (KUB) was
as accurate in diagnosing the source of hematuria
as an IVU and even more accurate in detecting
bladder tumors. We chose not to use the plain ab-
dominal film in an attempt to keep the imaging
studies to a minimum and to help contain the price
UROLOGY 57 (5), 2001
of the evaluation, since all patients underwent cys-
toscopy and those without a diagnosis with persis-
tent microhematuria after the initial evaluation
were to undergo IVU, as proposed in the algo-
rithm.
The correlation of the degree of microhematuria
with the presence of urologic disease has not been
clearly defined in published reports.16 –19 Some in-
vestigators have defined 2 to 3 red blood cells per
HPF as significant microhematuria20,21; other in-
vestigators have a more rigid definition of greater
than or equal to 1 red blood cell per HPF as signif-
icant hematuria.11,16,17,22,23 In other studies, signif-
icant microhematuria was defined as 6 or more red
blood cells per HPF.1,24 With all of this contro-
versy, we decided to use a widely accepted value of
3 red blood cells per HPF as significant microhe-
maturia.25
Urine cytologic analysis was performed on a sin-
gle voided specimen to evaluate for a neoplastic
process as the source of the microhematuria before
any radiologic or urologic procedures. Cytologic
analysis was positive in 2 patients, both with high-
grade TCC. The sensitivity of cytologic analysis is
dependent on multiple factors, including the num-
ber of urine specimens, the tumor grade, and the
skill of the cytopathologist.1,16,18,19 A specimen
would be expected to be positive in 10%, 50%, and
90% of patients with grade I, II, and III urothelial
tumor, respectively, and exceeds 80% in all pa-
tients with carcinoma in situ and more than 90% in
those patients with symptomatic carcinoma in si-
tu.26
We chose to wait 3 months before performing
IVU if cystoscopy and US were negative in patients
with persistent microhematuria. Although some
investigators decided to wait 6 months, we be-
lieved a shorter period would allow us to detect any
pathologic features sooner.27 Davides et al.17 dem-
onstrated that the cost of treating patients with
urologic cancer detected early compared with
treating patients in whom microhematuria had
been ignored for more than 1 year and who pre-
sented with other symptoms of urologic cancer was
five times greater in the group treated later.
Our study has several limitations. First, there
were almost twice as many women as men in the
study and the mean age of the individuals in the
study was only 58 years. This is problematic be-
cause urothelial cancer and RCC tend to occur in
older individuals (older than 65 years) with a 2:1
male/female ratio, making our study group less
likely to have urologic neoplasms. This selection
bias resulted from performing a prospective study
and enrolling the first 400 individuals who pre-
sented with microhematuria in the study. It may be
beneficial to complete a prospective study that en-
rolled only male patients older than 65 years of age.
UROLOGY 57 (5), 2001
Also, we only had a 3-month follow-up period
with a urologist during the study. Follow-up with a
urologist after 3 months was variable. After the
initial follow-up, the patients were monitored by
their primary care physicians who were instructed
to closely monitor these patients for recurrent mi-
crohematuria. The need to completely evaluate
and monitor patients with asymptomatic microhe-
maturia is not shared by all urologists. Howard and
Grolin,27 in a 10 to 20-year follow-up of 155 pa-
tients, showed that urothelial cancer did not de-
velop in their patients with a previous negative
workup for microhematuria. Additional evaluation
was done only if patients developed gross hematu-
ria, recurrent urinary tract infection, or changes in
voiding characteristics.
Another limitation is the assumption that no ev-
idence of hematuria at 3 months indicated no un-
derlying pathologic features in the 91 patients who
had a normal renal US without IVU and resolution
of their microhematuria. This is an inappropriate
assumption because urothelial tumors and RCC
can present with intermittent hematuria. Finally,
the percentage of urologic pathologic findings that
may have been missed by renal US but diagnosed
by IVU cannot be accurately extrapolated from our
study, since we did not perform IVU on all the
patients in the study. However, recent published
reports have shown US to be sensitive in detecting
masses, stones, cysts, and hydronephrosis of the
kidney and even more sensitive in detecting the
more common RCC than IVU.8 –11
CONCLUSIONS
The proper evaluation of microhematuria re-
mains controversial, and many investigators have
compared US to IVU in its evaluation. We evalu-
ated what study should be performed initially and
how individuals should be additionally evaluated.
Determining which study is superior was not ad-
dressed. We demonstrated that renal US could be
used initially with cystoscopy in the evaluation of
asymptomatic microhematuria as long as IVU is
considered in patients with persistent microhema-
turia. We believe this would decrease the overall
cost of the initial evaluation along with the mor-
bidity associated with IVU while at the same time
maintaining diagnostic accuracy.
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