Hematuria: Definition and screening test methods


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.

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 urological 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 considered positive.

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/μL or above.
  • <2> The urine sediment test involves examining the urine for erythrocytes and checking for the presence of erythrocyte casts and granulocyte casts. Attention is also directed to any atypical epithelial 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 estimate 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 performed, 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, cystitis, 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.

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)

Figure 1.

Flowchart for diagnosing microhematuria.

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, cystoscopy, CT, and in some cases intravenous pyelogram should be performed. In high-risk groups it may be appropriate to perform cystoscopy along with urine sediment testing, urine cytology, and abdominal (renal-bladder) ultrasound.

3-5 Monitoring the clinical course

If the etiology of hematuria has not been clearly elucidated, the clinical course should be monitored for three years to watch for malignancy. If there is any question of renal parenchymal disease, the patient should be referred to a nephrologist for observation.

4 Diagnosis of gross hematuria

4-1 Diagnostic flowchart (Fig. 2)

Figure 2.

Flowchart for Initial Diagnosis of Gross Hematuria.

  • 1) Medical history: Has the patient experienced intermittent hematuria? When did it appear? Was the hematuria accompanied by other symptoms?
  • 2) Urinalysis: Confirmation of hematuria. Are atypical cells present within the urine sediment?
  • 3) Urine cytology: Confirmation of the presence of atypical cells.
  • 4) Blood biochemical tests: prostate specific antigen (PSA) test in males 50 years of age or older, detailed testing for renal disease.
  • 5) Abdominal ultrasound: At initial screening and when monitoring the patient's clinical course.
  • 6) Cystoscopy: The flexible cystoscope has made it possible to monitor the bladder with no blind spots. Monitoring from the ureteral orifices can confirm the side of bleeding in the upper urinary tract.
  • 7) CT urography: Information that conventionally would have required both a CT scan and an intravenous pyelography can now be obtained from a single test, which is beneficial for the patient.
  • 8) MRI (MR urography, excretory MR urography): Useful for upper urinary tract imaging in patients with allergies to iodine contrast media and in patients with impaired renal function.
  • 9) Retrograde pyelography: Useful for upper urinary tract imaging in patients with allergies to iodine contrast media and in patients with impaired renal function.
  • 10) Urine cytology from the upper urinary tract: Useful for the diagnosis of urothelial cancer in the upper urinary tract.
  • 11) Ureterorenoscopy: Useful for detailed examination in cases of renal pelvic or ureteral filling defect. Lesions can be biopsied.

(Recommended in these guidelines, including for patients under treatment with anticoagulants.)

4-2 Monitoring the clinical course of gross hematuria in adults (Fig. 3)

Figure 3.

Monitoring the clinical course of gross hematuria.

  • 1) Careful follow-up monitoring for three years: At intervals of three to six months

Practically all conditions requiring treatment have been reported to develop and be diagnosed within three years after the appearance of hematuria.

  • Urinalysis

  • Urine cytology

  • Blood biochemical tests

  • Abdominal ultrasound

  • Cystoscopy

  • CT urography: as needed

The clinical course is to be monitored by performing urine sediment testing, urine cytology, and ultrasound twice annually.

4-3 Gross hematuria in children

The following tests are to be performed, with additional testing as needed. Because the risk of malignancy is low in children, particularly school-age children, we do not recommend the initial use of cystoscopy, which is a physically difficult procedure for children, or thin slice CT scanning, which subjects the patient to high doses of radiation. If hematuria recurs, these tests can be reconsidered. Hematuria of unknown etiology is considerably more common in children than in adults.

  • 1) Medical history: When was gross hematuria first evidenced? Has it been accompanied by symptoms such as abdominal pain or painful urination?
  • 2) Urinalysis: Confirmation of hematuria, evaluation of urine sediment for crystals, etc.
  • 3) Urine cytology: This test should be performed even though abnormal findings are rare in this age group.
  • 4) Urine biochemistry (calcium, uric acid, creatinine): Evaluation for hypercalciuria and hyperuricuria.
  • 5) Abdominal (renal-bladder) ultrasound: To be performed at the initial consultation whenever possible.

5 Diagnosing pediatric patients with microhematuria on the basis of school urine testing (Fig. 4)

Figure 4.

Flowchart for the diagnosis of pediatric hematuria.

(focusing primarily on pediatric patients with microhematuria detected through school urine screening)

5-1 Testing from renal disease secondary detailed testing categories

Of the results from school urine screening, those cases in which the abnormal findings are limited to hematuria will undergo further renal disease secondary detailed category testing as established by the local regional government Japanese A mode. At that time, the child's prior medical history and family medical history will be taken.

5-2 Evaluating red blood cell morphology in the urine

When the child is seen at a medical facility, urine red blood cell (RBC) morphology will be evaluated if at all possible.

5-3 Urine biochemistry and ultrasound

If urine RBCs are isomorphic (non-glomerular), one-time testing is to be performed for urine biochemistry (calcium, uric acid, creatinine) and renal-urinary tract ultrasound. Because ultrasound procedures are relatively inexpensive and easily tolerated by the patient, these procedures can also be performed if difficulties are encountered in assessing urinary RBC morphology.

5-4 Monitoring the clinical course

Because these findings may be indicative of early stage chronic nephritis, we recommend testing at least once a year at a medical institution, in addition to the annual school urine test.

5-5 Lifestyle counseling

The long-term prognosis for asymptomatic hematuria is excellent in almost all cases. This should be explained to the patient and family, and they should be counseled against excessive restrictions on exercise or other activities.