Urinalysis finally catches up
William Check, PhD
Sometimes asking a laboratorian what is changing in the field
of urinalysis produces a brief silence, followed by a remark such
as, "Urinalysis has kind of stayed urinalysis," or "Urinalysis is
not the most exciting and dynamic area in laboratory medicine." But
a minute of thought usually brings to mind important efforts being
made to improve the value of urinalysis to ordering physicians and
patients. These efforts range from assessing when urinalysis should
be ordered and how results can be made more reliable, to the introduction
of automation into microscopic analysis of urine, one of the few areas
of laboratory medicine that is still done manually in many hospitals.
"We can look at urinalysis from two different viewpoints," says
William Rock, MD, professor of pathology and director of the clinical
laboratory at the University of Mississippi Medical Center in Jackson.
In the first and most common circumstance, routine screening, "Results
of urinalysis are often not optimally taken advantage of by clinicians,"
Dr. Rock says. His biggest concern is that an important result will
be missed. "When urinalysis is part of a routine situation, physicians
expect it to be negative," Dr. Rock says. Because of this expectation,
"alertness is lowered and the results don’t get as much attention."
A meaningful step, then, in improving the use of urinalysis is to
encourage physicians to review the results of urinalysis every time
they order one.
In the second circumstance, urinalysis is requested because the
patient has signs and symptoms suggesting that something is wrong
with the urinary tract. In that case, urinalysis becomes more important.
Nephrologist Giovanni Fogazzi, MD, who directs the laboratory
of the renal unit at the Ospedale Maggiore of Milan, carries this
line of thought further. "Urinalysis is not generally ordered appropriately,"
he says. "It is a test that is abused. If it is done just for screening,
nobody cares. We know now that urinalysis is not for everybody,
but should be requested only on the basis of a clinical problem,
especially for the kidneys." The position that urinalysis should
be ordered selectively is incorporated into the latest ECLM-European
Urinalysis Guidelines, which Dr. Fogazzi helped formulate (Scand
J Clin Lab Invest. 2000;60[suppl 231]; www.pshp.fi/labnet/EUgroup.htm).
Improving the quality of urinalysis results is another concern,
says Timo Kouri, MD, PhD, associate chief physician at Oulu University
Hospital, Finland, and chairman of the European project that produced
the guidelines. Dr. Kouri notes that the computer maxim "Garbage
in, garbage out" applies as well to urinalysis. "People have been
putting in junk and then throwing up their hands because they don’t
know the relevance of the results that come out," he says. Improving
the quality of urinalysis results means improving every step of
the process, starting from the preanalytical phase, including specimen
collection and transport. "Every detail should be outlined within
a standardized operating procedure," Dr. Kouri says.
The most dramatic advance in urinalysis has been the evolution
of automated instruments to replace visual microscopic analysis
of formed elements in urine. "This has been the biggest change in
urinalysis in the last 20 years," says Edward Fody, MD, chief of
pathology at Erlanger Medical Center in Chattanooga, Tenn. "The
coming of automated particle analysis systems has revolutionized
Adds Dr. Kouri, "Automated analysis and counting of cells or particles
in urine, which may also include casts or bacteria, saves time and
improves precision of counting."
Gifford Lum, MD, assistant chief of Pathology and Laboratory Medicine
Service at the VA Boston Healthcare System, notes that the microscopic
examination of urine is one of the last areas of the laboratory
to be automated. "The problem has always been that manual microscopic
examination of urine was tedious, so it was not done uniformly,"
he says. He compares the situation to cell counting in hematology.
"Before the coming of automated hematology instruments, there were
protocols not to do differentials on all CBCs," he says. Now that
has changed. "We will see the same thing happening with urinalysis,"
Dr. Lum predicts. "When it gets automated with flow cytometry, it
will be done automatically regardless of the results of dipstick
"Urines have languished," says Jeri Walters, MT, technical supervisor
at ACL Laboratories, Milwaukee. "Now urinalysis is finally catching
up with the rest of the laboratory in technology and automation.
The latest technology operates much like an automated hematology
instrument," says Walters, referring to the Sysmex UF-100, a flow
cytometer that performs automated analysis of formed elements in
urine. "It works much like our five-part differential analyzer,
doing screens and throwing flags for abnormalities." Walters finds
that automated screening for cells and particles affects attitudes
as well as accuracy. "It changes how you think about results," she
says. "They are no longer ’crummy close-enough urine results.’"
Speaking of the other major automated instruments for analyzing
formed elements in urine, from IRIS Diagnostics, Dr. Rock says,
"This instrument has enabled us to automate and operate full time."
Bacterial culture, the third part of a complete examination of
urine, "seems to be the most common microbiology laboratory test
in the world," says Dr. Kouri. It used to be routine for every patient
with symptoms possibly attributable to urinary tract infection,
he says. But the new European guidelines classify low- and high-risk
patients and recommend routine cultures only for high-risk cases.
In the new European guidelines, emphasis is on "medical need"
rather than general screening. "In some parts of the world, people
think of urinalysis to be done for everybody," Dr. Kouri says. "Now
we think first of medical need, then cost versus benefit." For patients
with diabetes or hypertension, for example, a sensitive analysis
detecting proteinuria or albuminuria is becoming more frequent.
"For other patients, it may not be justified to study urine at all,"
Dr. Kouri says.
The state of public health care is another consideration. In Finland
every child is examined by a public health doctor annually, Dr.
Kouri says. In Japan, a child may not have an annual examination
unless the parents organize it. "In that case, urine screening may
be a replacement for a physician," he postulates.
The situation at Chicago’s Stroger Hospital of Cook County may
be similar. According to Mariano Yogore, MD, director of the hospital’s
Adult Emergency Services Testing Center, the hospital has one of
the largest emergency services in the nation, serving 120,000 patients
each year. About 45,000 of these patients have urinalyses. "I think
there is some overuse," Dr. Yogore says. "Because of our volume,
patients are first seen by triage nurses or physician assistants,
who may order urinalysis as soon as a patient is interviewed and
examined." Also, many patients are economically disadvantaged and
non-English speaking. In this setting, urinalysis may be used as
a screening examination or in lieu of a medical history.
In Italy, urinalysis is one of the most commonly requested tests,
says Dr. Fogazzi, who is the author of a monograph on the urinary
sediment (Fogazzi GB, Ponticelli C, Ritz E. The Urinary Sediment.
An Integrated View. 2nd ed. Oxford: Oxford University Press;
1999). It is ordered at every office visit and every hospitalization.
"This has practical and important consequences," he says. "In my
last workshop, three or four of the 10 physicians attending had
to do microscopic sediment analysis every day on at least 300 urine
sediments. This implies inevitably poor quality and unreliable results."
Under the best of circumstances, physicians are given a lot of
information and urinalysis is just one more small piece, says Dr.
Rock. He cites an article in JAMA about 10 years ago that
evaluated clinicians’ performance in reviewing the medical chart.
"Urinalysis was the least looked at item on the medical report,"
he recalls. To Dr. Rock, this does not prove that urinalysis is
overordered for screening. "If there was ever a test that you could
justify for screening, urinalysis is it," he asserts. In his view,
it quickly provides an assessment of a variety of functions. "If
it is normal or negative, we have eliminated certain diseases from
primary consideration," he says. "But," he reiterates, "you have
to look at it and pay attention to the results."
In the quest for better urinalysis results, written or
clear-cut oral instructions to the patient on how to collect a urine
sample is the first step. "Here in our unit we have written instructions,"
says Dr. Fogazzi. "They could be improved, but it is a start." Frank
illustrations on how to collect a midstream urine are available
in many languages on the same Web site as the European guidelines.
"It is now possible to instruct the patient and afterward ask whether
there were any problems in specimen collection," Dr. Kouri says.
In Finland, specimens are divided into two categories based on the
answer—qualified or non-qualified or unknown.
"There are standards for a midstream urine," acknowledges Dr.
Rock, "but it is very hard to get." To avoid contamination, he recommends
processing urine specimens in two hours and refrigerating if necessary.
"We use the criterion of three or more epithelial cells/high power
field," he says. If this threshold is exceeded, the results are
labeled "Interpret with caution." "We routinely report the number
of epithelial cells we see," he adds.
Walters agrees: "Getting clean-catch midstream samples is always
going to be a problem. Someone might give the patient a piece of
paper with instructions and assume they understand our technical
terms. Or someone explains it in 20 seconds." Health care providers
should be aware that they need to instruct patients better.
Dr. Yogore calls proper specimen collection "one of most important
things that has to be followed in an ER setting, where we are overwhelmed
with patients." Unfortunately, he says, "Many patients in the population
we serve may not understand the instructions." Diagrams are provided
at the nurses’ station but may not be sufficient. "Contamination
due to improper collection, especially with females, is an ongoing
problem," Dr. Yogore says. "It is reflected in the need for repeat
Another step in improving urinalysis results is to centralize
specimen collection and improve the transportation chain. In large
countries—the U.S., Canada, Russia, Australia, parts of France,
the United Kingdom—this requires effective preservation with
either boric acid or mercury-chloride-based preservatives, Dr. Kouri
says. He calls mercury chloride, often used in the U.S., "not very
customer friendly" and "toxic." Dr. Kouri published this year in
Clinical Chemistry (2002; 48: 900-905) an evaluation of a
commercial boric-acid-based solution showing that it preserves bacterial
counts for two to three days as well as leukocytes and particles
for visual microscopy and automated analysis. "In the future," he
predicts, "development will again go toward preservatives for bacterial
culture and test strips and particle analysis because of centralization
of health care and lack of laboratory technologists all over the
Walters favors Becton Dickinson preservative tubes for samples
not analyzed within one hour of collection, such as outreach work.
She uses either a tube with a camouflage top and conical bottom,
designed for routine urinalysis, or a gray-top tube, designed for
microbiology. Gray-top tubes preserve urine elements well, Walters
finds. "The biggest shift we saw [with gray-top tubes] was a slight
elevation in specific gravity," she says. "Shifts in other chemical
components were minor compared to leaving a specimen sit for 12
As with many other changes in laboratory medicine, enthusiasm
for automated analysis of formed elements in urine is driven to
a large extent by economic constraints and the shortage of medical
technologists. In this climate, microscopic analysis of urine tends
to be restricted. "Like a lot of laboratories at a time of decreasing
staff and increasing pressures to perform, we were following a protocol,"
says Leo Serrano, FACHE, CLSup (NCA), executive director of laboratory
services at West Tennessee Healthcare, Jackson. Microscopic examination
was not done if dipstick results were all within normal limits and
the urine was clear, unless the ordering physician requested it.
"Even so, we were doing more than 200 urine microscopies every day,"
Serrano says. "So we started looking for an automated method."
Two approaches dominate automated particle analysis. Sysmex instruments
are flow cytometers, using forward scatter to classify particles
by size and two fluorochromes—one that stains membranes and
the other nucleic acids—to differentiate cells or casts based
on their contents.
IRIS Diagnostics’ instruments route samples through a flow cell
where a digital camera captures images of each particle. Images
are displayed on a computer screen and an operator identifies and
classifies each element by touching the screen. A newer IRIS instrument,
the 900 series, filters images through neural network-based pattern
recognition software, which automatically classifies elements based
on morphological characteristics.
Dr. Kouri has published a validation study comparing the accuracy
of the Sysmex UF-100 to visual microscopy. He found that the instrument
improved precision and accuracy and saved time and labor. It was
equal to microscopy for red blood cells, white blood cells, and
bacteria, which is what clinicians want to know about in most cases
(Am J Clin Pathol. 1999;112:25-35). A study conducted by
Professor Joris Delanghe of the University of Ghent (Clin Chem.
1999;45:118-122) corroborated Dr. Kouri’s results.
Validation data on the IRIS 400 series were presented in abstract
form at 1991 (Abs #91) and 1994 (Abs #58) ASCP/CAP meetings. This
work showed that the IRIS was at least as sensitive as standard
manual methods for most abnormalities and possibly more sensitive
From the point of view of nephrologists, however, automated instruments
are not helpful, Dr. Fogazzi notes. "These instruments don’t reliably
distinguish subtypes of casts and do not discriminate tubular from
transitional—superficial and deep—cells," he says. "In
addition, they don’t recognize lipid particles at all, which are
a frequent finding in patients with nephrotic syndrome and may be
diagnostic for lipid storage disorders such as Fabry’s disease."
So a nephrologist would have to look at all specimens that have
any particles. "But for general laboratories, where several hundreds
of sediments are analyzed every day, and most sediments are normal
and only a fraction contain abnormal findings, to have an instrument
like that is useful," he says.
Dr. Fody bought a Yellow IRIS in 1984 when he was at the Little
Rock, Ark., VA hospital. It produced reliable results and turned
a workstation where none of the medical technologists wanted to
work into "a very desirable workstation," he says. Earlier this
year he purchased a Model 500 IRIS for his lab at Erlanger Medical
Center. "There is definitely a technologist interaction," he says,
"and there always should be." A technologist has to verify the instrument’s
judgments, but they find looking at the computer screen easier and
faster than looking through a microscope.
Dr. Rock has two IRIS instruments at the University of Mississippi
and is upgrading to the 500 series. "My technologists really like
the IRIS and how it works for them," he says. The operator uses
a pointer, finger, pencil eraser, or the like to touch each element
on the screen for each category. "If the urine is negative, the
process goes very quickly," he says. "If there are lots of formed
elements, such as forms highly suspicious of casts or crystals,
we would do a manual microscopic analysis." Manual microscopic analysis
is necessary in from 10 to 20 percent of cases.
Whether the instrument is labor saving is not the key factor,
in Dr. Rock’s view. "For us, the IRIS helped to define urinalysis
as a workstation running 24/7 with one operator," he says. "It lends
itself to late-night shifts where you have various levels of expertise."
Dr. Rock’s laboratory processes 300 to 400 urine specimens daily.
Every sample goes through both chemical and microscopic analysis.
"We have a large sick population and physicians want to hear all
negative microscopic results, particularly with oncology patients,"
Dr. Rock looked at an IRIS 900 series instrument, which is truly
walkaway in terms of loading, though it still requires a technologist
to look at images and verify classifications and do microscopy when
indicated. "We’ll reassess the 900 as our volume increases," he
At Stroger Hospital of Cook County, a large, new hospital has
just been built to replace the old one, and nearly all laboratories
will be integrated into a new central hospital laboratory. This
facility will have two IRIS 500 series instruments that will handle
about 65,000 urinalyses annually. A high percentage will get a microscopic
examination. Even though the IRIS 500 instrument does not batch
process, Dr. Yogore is confident it can manage the high volume because
of its reliability and speed.
"I myself have no experience with the IRIS," Dr. Yogore says.
He chose this vendor because the outpatient laboratory at Stroger
Hospital had been using an IRIS for several years. Most recently
the outpatient laboratory got a 900 series, but it has had problems
with the FESH unit, the front-end sample handler. "So," Dr. Yogore
says, "even though the 900 series can do batch testing, we selected
the -manual-loading 500 instrument. It is based on the 400 series,
which has a long history as a workhorse."
IRIS instruments save images, which is highly useful. The instruments
make it possible for the Stro-ger Hospital laboratory to compare
interpretation among different operators and standardize reporting,
Dr. Yogore says, which provides an excellent quality control mechanism
and a teaching tool.
In the laboratory at the VA Boston Healthcare System, Dr. Lum
has a Yellow IRIS that he inherited from another hospital when his
laboratory became the tertiary care center for the health system.
"My concern about the IRIS is that there is too much interaction
between operator and instrument," he observes. "A technologist has
to identify components such as WBCs, RBCs, casts, et cetera as they
come up on photo images. So I don’t really think it has freed up
any technical time or contributed to automation of urinalysis."
Flow cytometer-type instruments are the wave of the future, in
Dr. Lum’s view. Current flow cytometer-based instruments, such as
the Sysmex UF-100, are truly walkaway in terms of loading, he notes.
"I think the UF-100 is probably the way to go," Dr. Lum says. He
adds that flow cytometers can also do cell counts on several body
fluids, such as cerebrospinal, ascitic, and peritoneal fluids.
When Serrano was deciding on an automated instrument for urine
microscopies at West Tennessee Healthcare, he brought a Sysmex UF-100
into his laboratory and paralleled it with standard microscopic
examinations in an internal study. He took 3,000 dipstick-negative
urines and ran them through the UF-100. Anytime the UF-100 detected
what was considered a clinical abnormality—more than 5 WBCs/
µL, more than 3 RBCs/ µL, any casts, etc.—the specimen was
centrifuged and examined through the microscope. "Roughly 18 percent
of the 3,000 dipstick-negative urines had some sort of formed element
abnormality or the presence of some formed elements that we would
not have reported previously," Serrano says. "That got our attention."
The laboratory purchased a UF-100 about one year ago and now performs
flow-based microscopic analysis on every urinalysis, regardless
of dipstick results. "We have been very pleased with the findings,"
With the automated instrument, they were able to reduce staffing
in the area by one full-time equivalent. "Urinalysis microscopy
used to be a full-time assignment on day shift and evening shift
and part-time on night shift," Serrano says. Now it is an add-on
assignment on each of those shifts for the same person who does
manual analysis on differentials.
Originally Serrano set up the instrument so that flagged specimens
would be reviewed manually. "Now that we have confidence," he says,
"we set it up to autorelease most findings." Only certain flags
require validation. "We still have a person look at fine and coarse
granular casts and cellular formed casts," he says. "We trust the
instrument to detect RBCs and WBCs. We visually validate yeast and
yeast-like organisms." With this protocol, the number of microscopic
examinations has been reduced by about 80 percent, Serrano estimates.
At ACL Laboratories, Walters chose between the two automated instruments
for microscopic analysis in much the same way that several other
laboratorians did—based on the experience of a colleague.
ACL Laboratories is a large merged core laboratory and one of the
merged sites had a positive experience doing beta site testing with
the UF-100. "We were pretty confident there was nothing else on
the market at this time with that level of technology and sophistication
for urinalysis," she says. Previously she had had an IRIS 900 series
instrument, but, she says, "that was still very labor intensive.
It was better than manual, but still subject to technologist-to-technologist
variation and fatigue."
After about eight months, she finds the UF-100 advantageous. "A
big step up for urinalysis is the increase in precision you get
out of this technology," she says. "It is more reproducible than
manual methods, where there are too many variables." She finds that
the UF-100 saves about one FTE. "It depends on patient acuity,"
she notes. "If you have a lot of clear, colorless urines, they will
go through anything fast."
Walters has set up protocol to verify anything that has a possible
pathological finding, such as increased renal cells, pathological
casts, and the presence of yeast or sperm. "We will accept RBCs
and WBCs from the instrument," she says.
One possible screening criterion her lab has studied is the crystal
flag. "We weren’t sure if it was really significant," Walters says.
So she compared detection of abnormal samples with all flags set
except the crystal flag versus screening with the crystal flag activated.
Among 610 samples, overall sensitivity for abnormal samples without
the crystal flag was 96.9 percent and specificity was 89.8 percent,
with a false-negative rate of three percent. (The only samples missed
had yeasts without WBCs, suggesting contamination.) "So we really
feel the crystal flag was not significant," Walters concludes. As
a screening test, the negative clinical accuracy (negative predictive
value) was 99.4 percent, which, Walters says, "is right where we
In contrast to analysis of formed elements, which is being
applied more widely, microbiological culture should be used more
judiciously. According to the European guidelines, no urine testing
should be done in low-risk women—basically adult women with
recurrent cystitis or urgency symptoms or dysuria but without fever
and without known diseases predisposing to urinary tract infection
(UTI). "A rapid test, such as a test strip, is insensitive," Dr.
Kouri says, "and culture may be sensitive but it is useless." It
is usually possible to determine the organism without investigation,
based on the pathogens prevailing in the community, and to prescribe
antibiotics empirically. "Empiric treatment saves perhaps one-third
to one-half of urine bacterial cultures," Dr. Kouri says. All other
symptomatic patients belong to the high-risk group, whose specimens
should be sent for bacterial culture, including identification of
species and antimicrobial susceptibility testing.
Dr. Rock finds that some clinicians treat empirically based on
symptoms and results of urine chemistry. "If a patient is symptomatic
and the dipstick is positive for protein or leukocyte esterase or
nitrite-reducing bacteria, that is a presumptive diagnosis of a
bacterial UTI," he says. "If it is a first-time infection or an
uncomplicated UTI, treating empirically is all right," he says.
"But for repeated infections or in a patient with kidney disease
you would get a culture." Dr. Rock distinguishes between office
use of urinalysis and hospital or clinic use. "Office physicians
are more likely to use dipstick information as a basis for treatment,"
he notes, "while hospital-based physicians will more likely get
a microscopic examination."
In the future, Dr. Kouri foresees automated urine bacterial cultures,
as well as wider adoption of automated test strip measurement. "Fully
automated instruments for test strips already exist," he says. "For
urine bacterial culture, there are only some big robots in research
laboratories." However, he expects automation at the basic level
of growth and primary typing during the next 10 or 20 years.
For now, Dr. Rock emphasizes getting the most out of urinalysis
as it is currently done. He compares urinalysis to blood pressure
reading. "Both are important parts of patient management," he notes,
"but both need the physician to look at the result in the context
of the whole patient." If he had to stress one message, he says,
it would be, "Every time you order a routine urinalysis, be sure
to check it closely for useful information."
William Check is a medical writer in Wilmette, Ill.