International Journal of Urology (2008) 15, 281–284 doi: 10.1111/j.1442-2042.2008.02009.

x,

Guidelines

Hematuria: Definition and screening test methods

Eiji Higashihara,1 Tsutomu Nishiyama,1 Shigeo Horie,1 Ken Marumo,1 Tetsuya Mitarai,2 Tetsuo Koyama,2
Takeshi Matsuyama,3,6 Kiichi Ito4 and Tomoji Yuno5
Working Group for the Creation of Hematuria Guidelines
1
The Japanese Urological Association, 2The Japanese Society of Nephrology, 3The Japanese Society of Pediatric Nephrology, 4Japanese Society of Laboratory
Medicine, 5Japanese Association of Medical Technologists, and 6Ministry of Health, Labour and Welfare (MHLW) Scientific Research Fund-Supported Project
for Early Detection, Diagnosis, Treatment and Control of Pediatric Intractable Kidney and Urinary Tract Diseases

1 Hematuria: definition and screening test
methods
1-1 Definition
Hematuria, defined as the presence of red blood cells in the urine, is an
important symptom in the diagnosis and treatment of renal and urologi-
cal disease. A diagnosis of hematuria is generally made on the basis of
urine color, the use of qualitative and/or semiquantitative urine strips to
test for occult blood , and microscopic examination of urine sediment.
1-2 Urine sample collection
Generally, a midstream urine sample is used. Each specimen should be
clearly identified as either an ‘early morning’ or a ‘random’ sample.
1-3 Screening test methods
1) Urine strip method
Urine strips are used in hematuria screening to test for occult blood.
Reported values of (1+) (hemoglobin 0.06 mg/dL) or above is consid-
ered positive.
mate of the population with microscopic hematuria in Japan, based on
the incidence of hematuria and population reported in vital statistics
from the Ministry of Health, Labour and Welfare, would indicate five
million cases. The etiology of hematuria is related to age, sex and other
risk factors that contribute to hematuria. Consequently, secondary
screening tests and subsequent medical management should be per-
formed , taking into account such factors and the presence of specific
and non-specific medical condition for individuals or the cohort.
3 Diagnosis of microhematuria
3-1 Conditions associated with microhematuria,
and their incidence
Hematuria can originate anywhere within the kidneys or urinary tract.
Reports indicate that 2.3% of patients with microhematuria have renal
or urinary tract disease, and approximately 0.5% have urinary tract
malignancy. The most common conditions include glomerular disease,
urothelial cancer, renal cancer, prostate cancer, urinary calculus, cysti-
tis, prostatic hypertrophy, renal arteriovenous malformation, and renal
cysts. Among the diseases seen in patients who test positive for urinary
occult blood , urothelial cancer can be life-threatening.

2) Urine sediment method

<1> If the patient tests positive for urinary occult blood , additional
testing is required to confirm the erythrocyte count within the
urine. This is generally done by examining the urine sediment
under a microscope, with a count of 5 erythrocytes/high power
field (HPF) (1 field , 400¥ magnification) considered positive for
hematuria. Alternative methods include the use of uncentrifuged
urine in flow cytometry (FCM), with hematuria indicated by
findings of 20 erythrocytes/mL or above.
<2> The urine sediment test involves examining the urine for eryth-
rocytes and checking for the presence of erythrocyte casts and
granulocyte casts. Attention is also directed to any atypical epi-
thelial cells. If indicated , urine cytology is performed to confirm
whether cancer cells are present.
2 Epidemiology of hematuria
The incidence of microscopic hematuria increases with age, and the
incidence of hematuria in women is higher than that in men. An esti-
Correspondence: Eiji Higashihara MD, Kyorin University School of
Medicine–Urology, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan. Email:
ehigashi@kyorin-u.ac.jp
This is an English translation of text originally published in Japanese in
, pages 5–10, 2006, Japanese Urological Association.
Received 10 January 2008; accepted 10 January 2008.
3-2 Cases in which glomerular lesions are
suspected
It is important to distinguish between glomerular hematuria and non-
glomerular hematuria. In the following circumstances, the patient
should be referred to a nephrologist.
<1> Cases in which hematuria is accompanied by proteinuria
<2> Cases in which hematuria is detected both in early morning urine
and in randomly collected urine samples, persistent hematuria is
routinely detected from multiple urine samples, and glomerular
hematuria is present
3-3 Risk factors for urothelial cancer
Risk factors for urothelial cancer include male gender, 40 years of age
or older, history of smoking, exposure to chemical substances, history
of urological disease, painful urination, urinary tract infection, and
extensive use of analgesics. Patients to whom these risk factors
apply are at high risk for urothelial cancer, and should be monitored
accordingly.
3-4 Test methods (Fig. 1)
The standard methods used to diagnose the etiology of microhematuria
are urine sediment testing, urine cytology, and abdominal (renal-
bladder) ultrasound. If these test findings indicate abnormalities,

© 2008 The Japanese Urological Association 281

GUIDELINES

Test strip method: Urinary occult blood (+) or above, proteinuria (-)

Abnormal findings on urinalysis

Testing of sediment from fresh randomly collected urine

Confirmation of abnormal urinalysis findings

RBC ? 5/HPF RBC ? 4/HPF

No risk factors Risk factors present

Etiology
Abdominal ultrasound Hemoglobinuria or myoglobinuria present?
Abdominal ultrasound
Urine cytology
Urine cytology
Cystoscopy (as appropriate)

No
abnormal
findings Abnormal findings
Abnormal findings
No abnormal
findings

Tests for urinary protein, dysmorphic erythrocytes CT, IVU if appropriate

in the urine, erythrocyte casts, blood pressure,
blood biochemistry (CH50, C3, C4, IgG, IgA)
Serum CPK,
Check for
urinary
hemolytic disease
myoglobulin assay
No abnormal No abnormal
Abnormal findings Abnormal findings
findings findings

Check for
Retest urine
conditions such as
sediment
Definitive rhabdomyolysis
diagnosis Periodic retesting
(including kidney
biopsy)
Risk Factors:
Male 40 years of age or older
History of smoking
Exposure to chemical substances
Renal Continued for 3 Continued for less Gorss hematuria
parenchymal years or more than 3 years Urological disease
disease Dysuria
History of urinary tract infection
Extensive use of analgesics (phenacetin)
History of pelvic irradiation
History of treatment with cyclophosphamide
Possibility of renal
Periodic detailed
parenchymal
testing
disease

Malignancy
Urinary calculus
Renal cysts
Other
Fig. 1 Flowchart for diagnosing microhematuria.

cystoscopy, CT, and in some cases intravenous pyelogram should 6) Cystoscopy: The flexible cystoscope has made it possible to
be performed. In high-risk groups it may be appropriate to perform monitor the bladder with no blind spots. Monitoring from the
cystoscopy along with urine sediment testing, urine cytology, and ureteral orifices can confirm the side of bleeding in the upper
abdominal (renal-bladder) ultrasound. urinary tract.
7) CT urography: Information that conventionally would have
required both a CT scan and an intravenous pyelography can
3-5 Monitoring the clinical course
now be obtained from a single test, which is beneficial for the
If the etiology of hematuria has not been clearly elucidated , the clinical patient.
course should be monitored for three years to watch for malignancy. If 8) MRI (MR urography, excretory MR urography): Useful for upper
there is any question of renal parenchymal disease, the patient should urinary tract imaging in patients with allergies to iodine contrast
be referred to a nephrologist for observation. media and in patients with impaired renal function.
9) Retrograde pyelography: Useful for upper urinary tract imaging
4 Diagnosis of gross hematuria in patients with allergies to iodine contrast media and in patients
with impaired renal function.
4-1 Diagnostic flowchart (Fig. 2) 10) Urine cytology from the upper urinary tract: Useful for the diag-
1) Medical history: Has the patient experienced intermittent hema- nosis of urothelial cancer in the upper urinary tract.
turia? When did it appear? Was the hematuria accompanied by 11) Ureterorenoscopy: Useful for detailed examination in cases of
other symptoms? renal pelvic or ureteral filling defect. Lesions can be biopsied.
2) Urinalysis: Confirmation of hematuria. Are atypical cells present (Recommended in these guidelines, including for patients under treat-
within the urine sediment? ment with anticoagulants.)
3) Urine cytology: Confirmation of the presence of atypical cells. 4-2 Monitoring the clinical course of gross
4) Blood biochemical tests: prostate specific antigen (PSA) test in hematuria in adults (Fig. 3)
males 50 years of age or older, detailed testing for renal disease.
5) Abdominal ultrasound: At initial screening and when monitoring 1) Careful follow-up monitoring for three years: At intervals of three
the patient’s clinical course. to six months

282 © 2008 The Japanese Urological Association

 Guidelines

Gross hematuria (sustained or intermittent)

Detailed testing, regardless of whether the patient is
taking anticoagulants

Detailed patient history

Is hematuria intermittent?
Date of hematuria onset
Are concomitant symptoms present ?
Etc.

Urinalysis: Confirmation of hematuria. Are atypical cells

present in urine sediment? In patients with allergies to iodine
Abdominal ultrasound contrast media or with impaired renal
Urine cytology function:
Blood biochemical tests MR uroography, excretory MR
Males 50 years of age and older: PSA (prostate specific urography, retrograde pyelography,
antigen) test Urine cytology from the upper urinary tract
Cystoscopy

In patients having no allergies to iodine contrast media

and showing normal renal function:
CT Urography:
CT urography using multi-detector row CT in combination
with intravenous pyelography, or
CT-only CT urography

Possible abnormal findings in the

No findings of urological disease
upper urinary tract

Ureterorenoscopy, urine cytology Detailed testing for renal disease

from the upper urinary tract

No abnormal
Abnormal findings
findings

Fig. 2 Flowchart for Initial Diagnosis of Careful follow-up

Definitive diagnosis
monitoring for 3 years
Gross Hematuria.

Careful follow-up monitoring for 3 years: At intervals of 3-6 months

• Urinalysis No abnormalities
• Urine cytology
• Blood biochemical tests
• Abdominal (renal-bladder) ultrasound
• Cystoscopy Low probability of urological disease
• CT urography: as needed

Follow-up monitoring twice annually

Abnormal findings Abnormal findings

Fig. 3 Monitoring the clinical course of

Definitive diagnosis Referral to meidcal specialist
gross hematuria.

Practically all conditions requiring treatment have been reported to Abdominal ultrasound
develop and be diagnosed within three years after the appearance of Cystoscopy
hematuria. CT urography: as needed
Urinalysis 2) Monitoring the clinical course after three years
Urine cytology The clinical course is to be monitored by performing urine sediment
Blood biochemical tests testing, urine cytology, and ultrasound twice annually.

© 2008 The Japanese Urological Association 283

GUIDELINES

Findings of hematuria

Through school urine test Other than through school urine test

Detailed testing required

Regional renal disease
Medical Institution
tertiary detailed testing

Findings of mild hematuria Urine RBC morphology

(5-9/HPF) to be managed
within the school urine
testing system
Isomorphic Dysmorphic (atypical)

No abnormal findings Monitoring with

Ultrasound particular attention
Urine biochemistry to proteinuria
(ultrasound)

Abnormal findings
If urinary protein
Renal biopsy to be Fig. 4 Flowchart for the diagnosis of
cannot be detected,
Differential performed if
the clinical course is
diagnosis urinary protein
to be monitored
pediatric hematuria.
level rises
periodically

4-3 Gross hematuria in children disease secondary detailed category testing as established by the local
regional government Japanese A mode. At that time, the child’s prior
The following tests are to be performed , with additional testing as medical history and family medical history will be taken.
needed. Because the risk of malignancy is low in children, particularly
school-age children, we do not recommend the initial use of cystos-
copy, which is a physically difficult procedure for children, or thin slice 5-2 Evaluating red blood cell morphology
CT scanning, which subjects the patient to high doses of radiation. If in the urine
hematuria recurs, these tests can be reconsidered. Hematuria of
When the child is seen at a medical facility, urine red blood cell (RBC)
unknown etiology is considerably more common in children than in
morphology will be evaluated if at all possible.
adults.
1) Medical history: When was gross hematuria first evidenced? Has it
been accompanied by symptoms such as abdominal pain or painful
5-3 Urine biochemistry and ultrasound
urination?
2) Urinalysis: Confirmation of hematuria, evaluation of urine sedi- If urine RBCs are isomorphic (non-glomerular), one-time testing is to
ment for crystals, etc. be performed for urine biochemistry (calcium, uric acid , creatinine)
3) Urine cytology: This test should be performed even though and renal-urinary tract ultrasound. Because ultrasound procedures are
abnormal findings are rare in this age group. relatively inexpensive and easily tolerated by the patient, these proce-
4) Urine biochemistry (calcium, uric acid , creatinine): Evaluation for dures can also be performed if difficulties are encountered in assessing
hypercalciuria and hyperuricuria. urinary RBC morphology.
5) Abdominal (renal-bladder) ultrasound: To be performed at the
initial consultation whenever possible.
5-4 Monitoring the clinical course
5 Diagnosing pediatric patients with
Because these findings may be indicative of early stage chronic nephri-
microhematuria on the basis of school
tis, we recommend testing at least once a year at a medical institution,
urine testing (Fig. 4)
in addition to the annual school urine test.
(focusing primarily on pediatric patients with microhematuria detected
through school urine screening)
5-5 Lifestyle counseling
5-1 Testing from renal disease secondary detailed
testing categories The long-term prognosis for asymptomatic hematuria is excellent in
almost all cases. This should be explained to the patient and family, and
Of the results from school urine screening, those cases in which the they should be counseled against excessive restrictions on exercise or
abnormal findings are limited to hematuria will undergo further renal other activities.

284 © 2008 The Japanese Urological Association