In urinalysis, automated microscopy making the difference

Ann Griswold, PhD

March 2014—Traditional urinalysis is messy. It’s tedious. It’s prone to variability. It’s nicknamed the “ugly stepchild” of the laboratory. Many are quick to note that it’s just a screening tool—with an emphasis on “just.”

But in recent years, urinalysis has been quietly tiptoeing into a new era. “We’re in the period of resurgence, using automated urine microscopics and urine chemistry to their full potential,” says Keri Donaldson, MD, assistant professor of pathology, medical director of hematology and thrombosis, and medical director of molecular diagnostics at Pennsylvania State University’s Milton S. Hershey Medical Center.

While automated methods for urine chemistry aren’t all that new, automated microscopy is transforming laboratories by allowing for more accurate, efficient, and standardized results.

But long before the automation, urinalysis once occupied a high position on the medical totem pole. “Even before there were such things as doctors, people were looking at the color of urine, the consistency of urine, the smell of urine,” Dr. Donaldson says.

That intense interest in urinalysis lasted well into the 20th century. “Decades ago, we had a golden time when urinalysis was very, very important and people were talking about blood versus urine. But over the years, people took a fair amount of what you could learn from urine for granted,” Dr. Donaldson says. “Newer diagnostic tests were introduced that are more descriptive and more specific than some of the findings that were historically available for urinalysis, and the focus on urine slipped away.”

The appreciation for urine didn’t disappear entirely, of course. It can reveal an array of information about the broad clinical picture.

“Our facility is a cancer hospital, so urinalysis ranks really high on the value scale,” says Annabelle B. Herrera, CLS, MT(ASCP), hematology supervisor of the clinical laboratory at the University of Southern California’s Norris Comprehensive Cancer Center. “Our clinicians monitor the protein content of the urine, for example, to determine if a patient can start chemotherapy. If the esterase is negative and you see a lot of white cells, then you suspect there might be some tumor cells. If they’re positive for esterase, you know they’re neutrophils and it could be an infection.”

Nancy Brunzel, MS, MLS(ASCP), author of Fundamentals of Urine and Body Fluid Analysis and assistant professor of clinical laboratory science at the University of Minnesota, calls urinalysis a “fluid biopsy of the kidney.”

“Urine is valuable, wonderful. There’s no other biopsy of an organ that we can get that’s noninvasive. In fact,” she says, “urinalysis gives you a good overview of what’s going on in several organ systems.”

One of the most valuable components of urinalysis—microscopy—continues to be performed by hand at many institutions, even large medical centers. Manual urine microscopy can be a long and tedious process with results that vary by laboratorian.

“As laboratorians, we need to more carefully adhere to the microscopic protocol written for our laboratory so that we’ll get the same result regardless of whether I’m doing the urinalysis or it’s done by a brand-new laboratorian, fresh out of school,” Brunzel says.

Individual labs strive to standardize urinalysis results by establishing reference ranges for their patient populations, reporting the number of blood cells per high-powered field. “The problem is that the number of cells you’re going to see per high-powered field depends on the method you use to get to that microscopic examination,” Brunzel says. “That varies all over the place.”

“When I got into the profession in the mid-’70s, urine was collected at the patient’s bedside. It might sit there for a couple hours, or it might get out to the nursing station and sit there even longer. When it got to the laboratory and back into the area that did the urinalysis testing, it might sit on the counter or get stuck in the refrigerator,” Brunzel recalls. “Then you took a well-mixed urine sample, plopped a drop on the slide, put a coverslip on it, and looked at it under the microscope. It was all very qualitative.”

Not much has changed in that regard, she worries. It’s still tricky to standardize the results of manual microscopy across institutions, given the myriad variations in the volume of urine being spun down, the speed and duration of centrifugation, and the volume of supernatant used to resuspend the sediment.

But even if all of those variables were held constant, Brunzel notes, other confounding factors exist. The microscope’s field of view may vary in size, for one. “Unfortunately, the oldest microscope in the lab is going to be in urinalysis. The scope that hematology no longer needs: ‘Oh well, it can go in urinalysis; they don’t need the greatest microscope.’”

Moreover, the number of high-powered fields observed can differ depending on how much time a laboratorian devotes to the slide. “If you’re sitting there with a rack of 20 urine samples, you’re not going to spend as much time on each one as if you had only three urine samples,” says Denise Gordon, MT(ASCP), hematology supervisor at Holy Name Medical Center, Teaneck, NJ. “You might hurry through it; you might not look at as many fields as you should.”

Automated urine microscopy has helped to achieve that goal. In recent years, automation has had a tremendous impact by allowing labs to standardize and improve the accuracy of urinalysis results. “We don’t have to worry about differences between techs reading a specimen, or the area of the slide they’re reading,” Gordon says.

Until recently, Gordon’s lab relied on a manually loaded Clinitek 500 instrument for urine chemistry, and performed labor-intensive manual microscopics on every positive specimen. A 1,000-bed medical center in a neighboring town continues to perform manual urine microscopy, she says, but at Holy Name, the workload became unsustainable. A single laboratorian was responsible for the coagulation and urinalysis workbenches, and he couldn’t keep up with the barrage of urine samples, especially when the hospital partnered with a large courier service. “We were processing about 90 urine samples a day. We were literally drowning in urine,” Gordon says. “As a manager, I found myself helping at the bench on many, many days, because it just wasn’t feasible for one person to do it all.”

Her lab purchased an AUWi system, which links the Clinitek Atlas Automated Urine Chemistry Analyzer to the Sysmex UF-1000i Urine Particle Analyzer. Racks containing urine specimens can be loaded into the Atlas, which automatically pipettes samples onto dipsticks and prints the urine chemistry results. Positive samples are sent to the UF-1000i, where the specimen is aspirated and subjected to flow cytometry. The system has transformed how her lab operates, she says. “Automating urinalysis has been the biggest change in my department in the past 10 years.”

“It’s been a godsend, because one person can now handle that bench easily. They can do the work and not be frustrated and overworked. It’s manageable,” she says. The system’s autoverification steps have proved particularly helpful. “Even lowering a turnaround time by one to two minutes can be instrumental.”

The application of flow cytometry to urinalysis was a game-changer, Gordon says. “Whoever took that next step was a genius.”

Though flow cytometry has been used in hematology assays for many years, it took a long time for the technology to transfer to urinalysis. Many hematology instruments offer body fluid analyses but are highly impractical to use for urinalysis, says Lorraine C. Smith, MBA, SH(ASCP), hematology technical leader in the Department of Pathology and Laboratory Medicine at the Medical Center of Central Georgia./p>

“Body fluid analysis is done in the urinalysis area. If you have a fairly decent-sized laboratory, it can get tedious for the urinalysis person to interrupt their workflow by going all the way over to the hematology instruments to run a fluid,” she says. “The second thing is that hematology instruments are meant to count thousands of white blood cells and thousands of red blood cells, but body fluids can have very few numbers of cells.”

Having a body fluid module on the urinalysis instrument means one person can perform both urine analyses and body fluids, and the system can be designed to detect and count very few cells.