Hematuria
Hossein Hamidi
Nephrologist
Hematuria
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Hematuria is the excretion of abnormal amounts of red
blood cells (RBCs) into the urine. Normal individuals
excrete about 1 million RBCs per day in their urine. When
translated to the sediment of a spun urine specimen, this
equates to about 1 to 3 RBCs per high-power field (HPF).
Therefore excretion of more than 3 RBCs per HPF is
abnormal and may warrant further evaluation.
Asymptomatic “microscopic hematuria” is very common ;
it may be detected in up to 13% of adults.
Routine screening of healthy individuals for the presence
of hematuria is not recommended by the U.S. Preventive
Services Task Force.
Hematuria
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Gross hematuria may first be detected by a change in urine
color. Microscopic hematuria can be detected by dipstick
methods, microscopic examination, or both.
Dipstick methods may be applied as diagnostic tests in
patients with known kidney disease or as screening tools in
healthy or high-risk individuals.
The U.S. Preventive Services Task no longer recommends
screening for occult hematuria in the general population.
Even when the urine is red, or when a dipstick screening test
result is positive, the sediment should be examined to deter
mine whether red cells are present. The presence of other
pigments such as free hemoglobin and myoglobin can
masquerade as hematuria.
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When such testing reveals hematuria, the person’s age,
gender, race, medical history, and physical findings should
be considered in deciding whether to further evaluate this
finding and, if so, in determining the most appropriate
diagnostic studies and the sequence in which they should be
performed.
Asymptomatic microscopic hematuria should be confirmed
in at least two of three midstream clean - catch voiding's.
If microscopic hematuria spontaneously resolves, evaluation
decisions are strongly influenced by the clinician’s index of
suspicion.
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Gross hematuria, especially if clots are passed, usually
indicates a urologic source of bleeding.
Even a single episode of gross hematuria mandates
evaluation.
The most common cause of gross hematuria in young
women (<40 years of age) is urinary tract infection (UTI).
Malignancy must be strongly considered and ruled out by
appropriate studies in older patients.
Brown, “Coca-Cola”–colored, or smoky urine with RBCs
present on micros-copy is very suggestive of a glomerular
source of bleeding.
History and Review of Systems
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Three major factors influencing the workup are the
patient’s gender, race, and age. The common causes of
hematuria in children and young adults are much different
than those in older individuals.
Hematuria in adults older than 40 years (some experts
propose an age cutoff of older than 50 years) must be
considered a sign of malignancy.
Hypercalciuria , and less commonly hyperuricosuria,
cause hematuria frequently in children but less commonly
in adults.
Hematuria due to UTI is much more common in women ,
whereas older men may bleed from the prostate.
History and Review of Systems
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The combination of hematuria with fever, dysuria, or
flank pain, or a prior history of these symptoms raises the
likelihood of infection, stones, or malignancy.
When a patient with hematuria has family members with
renal failure, polycystic kidney disease or Alport ’s disease
should be considered. Familial hearing loss, especially in
male relatives, also suggests Alport’s disease. A very
common cause of otherwise unexplained asymptomatic
familial hematuria is thin basement membrane disease.
Hematuria sometimes occurs after vigorous exercise or
participation in contact or noncontact sports .
History and Review of Systems
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Travel history may be very important as, for example, when
hematuria develops in patients who have traveled to areas
where Schistosoma haematobium infection or tuberculosis
is endemic.
Bleeding disorders and anticoagulants will cause any
pathologic GU structures such as malignancies to bleed
more readily. This is especially common in older patients.
A history of cigarette smoking (or second-hand smoke
exposure) increases the risk of bladder cancer twofold to
four fold.
History and Review of Systems
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Occupational exposure to aniline dyes and aromatic amines
and amides; treatment with some chemotherapeutic agents
such as cyclophosphamide and mitotane; and radiation to
the pelvis increase the risk for uroepithelial cancers.
A recent history of pharyngitisfol lowed by hematuria raises
the possibility of glomerulonephritis with synpharyngitic
bleeding. Chronic glomerulonephritis, most commonly
immunoglobulin A (IgA) nephropathy, is often exacerbated
by an upper respiratory tract infection and may result in
gross hematuria. This is distinct from post streptococcal
glomerulonephritis, which occurs 2 to 6 weeks following
the infection.
History and Review of Systems
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With gross hematuria, a history of initiation hematuria
suggests a urethral source, whereas termination hematuria
is suggestive of bladder neck or prostatic urethra pathology.
Blood clots in some the urine usually denote structural
urologic pathology.
Physical Examination
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Evaluation of blood pressure and volume status is especially
important when glomerulonephritis is a consideration.
If palpation of the abdomen reveals a mass, a renal tumor or
hydronephrosis may exist.
A palpable bladder after voiding indicates obstruction or
retention.
Atrial fibrillation raises the possibility of renal embolic
infarction, especially if the patient has flank pain.
Costovertebral angle tenderness is also suggestive of
pyelonephritis, nephrolithiasis, or ureteropelvic junction
obstruction.
Physical Examination
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A bruit over the kidney suggests a vascular cause.
Careful genital and rectal examination is necessary to
diagnose prostatitis, prostate cancer, epididymitis, meatal
stenosis, and other structural causes of hematuria .
Laboratory Tests
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A diagnosis of gross hematuria is suggested by red or brown
urine. Only about 1 mL of blood causes 1 L of urine to
become red. However, many substances other than RBCs can
produce. red or brown urine. Many chemicals, medications,
and food metabolites can produce a spectrum of urine colors.
Laboratory Tests
Laboratory Tests
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A chemical test for hemoglobin is very helpful in
distinguishing among these possibilities.
The most commonly used method of testing the urine for
blood is the urine test strip or dipstick, which utilizes the
peroxidase-like activity of hemoglobin to generate a color
change.
The test strip does not react with most nonhemoglobin
pigments that can color the urine.
In addition to detecting the hemoglobin within RBCs,
however, the test reaction yields a positive result with free
hemoglobin and myoglobin.
Laboratory Tests
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It is crucial to separate hematuria caused by glomerular
abnormalities from bleeding due to other pathologic kidney
conditions (tumors or cysts) or pathologic processes distal to
the glomerulus (interstitial disease, stones, or tumors, or
other processes affecting the renal pelvis, ureters, bladder,
urethra, prostate, or other lower GU system structures).
When blood originates from glomeruli, the RBCs pass
through the length of the renal tubules, where they are
subjected to marked changes in osmolality, ionic strength,
pH, and other forces. Compression of the RBCs together with
urine proteins creates RBC casts and identification of these
casts on microscopic examination is excellent evidence of
glomerular bleeding. Although quite specific, RBC casts often
are not seen even with definite glomerular bleeding.
Laboratory Tests
Laboratory Tests
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A more common helpful finding in glomerular bleeding is the
identification of dysmorphic RBCs of varying shape and sizes
with blebs, budding, and especially the vesicle-shaped
protrusions that characterize acanthocytes. For dysmorphic
RBCs to be an excellent indicator of glomerular bleeding,
most of the urine RBCs should be affected.
Acanthocytes are quite specific, however, and if they
represent more than 5% of the RBCs, this is very a suggestive
sign of glomerular bleeding.
Laboratory Tests
Laboratory Tests
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Another indication that bleeding is more likely of glomerular
origin is coexistent significant proteinuria (>0.5 g/day or >0.5 g
protein per gram of creatinine). The presence of pyuria with
hematuria suggests inflammation or infection and warrants a
urine culture.
Urine cytologic analysis is indicated when otherwise
unexplained hematuria is documented. It has good specificity
when results are positive and a sensitivity of about 80% for
bladder cancer but a much lower sensitivity for upper tract
malignancy.
Imaging
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When hematuria is not believed to be of glomerular origin,
then computed tomography (CT) with and without
intravenous (IV ) contrast is currently the preferred initial
imaging modality to evaluate microscopic and gross
hematuria and has largely replaced intravenous pyelography
(IVP).
CT urography has excellent sensitivity for stones, identifies
most kidney tumors, and reveals other non–GU tract
abdominal pathologic processes. The major downside of a
CT scan is the need for IV contrast and the significant
radiation exposure.
Imaging
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If CT cannot be done, then renal ultrasonography is the next
best initial imaging test. If the explanation for hematuria is
not evident on the initial study, the next diagnostic imaging
test to perform is cystoscopy.