Urinalysis: Efficiency, utility, and the ‘movement in the field’

December 2021—Four experts met on an Oct. 12 call to talk with CAP TODAY about urinalysis—the newest platforms, what labs need, labor solutions. CAP TODAY publisher Bob McGonnagle asked the questions. Providing their perspectives were Matthew Rhyner, PhD, MBA, Beckman Coulter; Jason Anderson, MPH, MT(ASCP), Sysmex America; Megan Nakashima, MD, Cleveland Clinic; and Keri Donaldson, MD, MSCE, Solvd Health and Penn State. Here’s what they had to say.

CAP TODAY’s guide to urinalysis instruments begins here.

Matt Rhyner, tell us about the exciting news we heard from Beckman Coulter at AACC.
Matthew Rhyner, PhD, MBA, VP and general manager, urinalysis, Beckman Coulter: We were excited to launch our DxU Iris integrated workcell featuring new versions of our digital microscopy and chemistry analyzer. It brings together workflow enhancements for our customers from a software and hardware perspective while retaining what they like about the digital microscopy platform, in particular with helping reduce manual reviews and making sediment analysis under a microscope unnecessary. We offer new zooming features and software workflow features, an enhanced aspiration module, and load/unload stations for higher-capacity customers. Installations will start this month.

Jason Anderson, is Sysmex seeing a need to integrate platforms within a network and have scalable platforms?
Jason Anderson, MPH, MT(ASCP), senior product manager, urinalysis solutions, IVD product marketing, Sysmex America: We see continuing demand for scalable and integrated laboratory testing solutions, and urinalysis is no exception. Our customers desire standardized technology from test strips to urine particle counting to ensure the comparability and continuity of results from their large core labs to their smaller stat labs and clinics. Our UN-Series Automated Urinalysis Solution is unique in that it employs scalable analyzer modules, and with this modular design, health networks can build right-size urinalysis solutions to fit their workflow needs. In addition, Sysmex will introduce the Care­sphere Workflow Solution for Urinalysis in the near future. With this technology, our customers will be able to further drive efficiencies in urinalysis processes and workflow across their organization through rule standardization, on-demand digital information, and management reporting capabilities.

Megan Nakashima, tell me about your need for and experience with integrated, scalable platforms at Cleveland Clinic, not only in the laboratories you run but in the institutions you serve within the network.
Megan Nakashima, MD, medical director, automated hematology, and staff pathologist, Cleveland Clinic: We see the need for being able to flex workflow wherever we can within a site, and if possible between sites. Like a lot of large systems, we have not only hospitals but also a plethora of small clinical sites that may or may not have the space or expertise to do this type of testing. In addition to being able to network one analyzer between people, having a more harmonized system that is scalable is also nice. If you have a line that uses the same strips—that goes from a basic strip reader to the full UF system—that to me has value.

Keri Donaldson, one of the themes we’ve always had is whether it’s possible to do more with urinalysis in terms of the total clinical care of the patient. Do you have a feeling about that?
Keri Donaldson, MD, MSCE, CEO, Solvd Health, and director of clinical genomics, Institute for Personalized Medicine, Penn State College of Medicine and Milton S. Hershey Medical Center: A significant amount of data is generated on somewhat of a ubiquitous fluid sampled commonly within the hospital system. And Beckman Coulter and Sysmex have moved the automation significantly as well as the reproducibility and the large amount of information that’s generated from these cells, sample to sample. It allows for the ability to ask additional questions or get clinically meaningful results from the same sample.

We have done historic early data work on using the images, whether they are images generated on a specific bacteria that could be isolated or overall the data generated from flow cytometric analysis, to talk about the types of bacteria present or not present. We did early work with Sysmex Japan talking about the type of bacteria that’s present and starting to move toward resistance profiles. None of that work is clinical in the U.S. yet. But once you talk about high-throughput, highly reproducible data points in the urine, there is more clinical information in the samples.

Matt, can you speak about the scalability of Beckman Coulter urinalysis solutions across larger networks and geographies?
Dr. Rhyner (Beckman Coulter): We offer that through our clinical informatic solutions. Specifically, our middleware solution allows for harmonization of processes across sites and within hospitals. We have a Command Central feature that allows multiple work­cells to be operated from a single point within a single hospital. We have a variety of solutions that harness advanced software tools to help with scalability, flexibility, and standardization. Our partnership in the U.S. with Arkray offers semiautomated and fully automated urine chemistry strips that are fully harmonized. So we offer a variety of solutions from small satellite hospitals to larger core labs, higher-volume facilities.

Megan, following the discussion from Keri, is it your view that urinalysis through the better analysis of what we’ve identified will prove to offer more clinical value?
Dr. Nakashima (Cleveland Clinic): There are a lot of possibilities. Flow cytometry in general is such a powerful tool that I have a feeling we’re not leveraging it enough in many different fields, particularly this one. At the same time, we’re seeing work being done with image analysis. If you were to go straight to an imaging-type system, there could be room there to get more data from what you’re looking at.

A standard desire or demand in urinalysis has always been to lower the percentage of manual reads. Megan, what’s your current manual review rate at Cleveland Clinic?
Dr. Nakashima (Cleveland Clinic): I believe that number is three percent—very low.

Jason, is three percent a possible outcome for anyone, not just specialists, using your instrumentation and software?
Jason Anderson (Sysmex): Correct. With our UN-Series solution, the brunt of the traditionally manual urine microscopic work is done automatically via fluorescent flow cytometry technology. Think of it as being similar to an automated differential in hematology—we’re doing that with urinalysis. We’re able to, in a standard, precise, and accurate way, measure and enumerate those particles. And for any particles that need to be subclassified, like crystals and pathologic casts, we have optional microscope-quality digital imaging to automate urine particle location for efficient confirmation when needed. We eliminate the need for manual microscopy with those two methodologies.

Matt, same question: Can you approach this rate of three or four percent?
Dr. Rhyner (Beckman Coulter): Yes, we have several case studies with those exact figures.

There are opportunities to improve the on-screen reviews and the amount of user interaction. We’re talking about driving down the number of touches required to produce reliable clinical results, at least in the standard urinalysis domain.

What Dr. Donaldson brought up about the additional information that could be derived from urine is interesting. Right now we report quite a few subcategories of particles, not all of which doctors use clinically; they use a much smaller subset. But medical technologists like all that information, so it’s a question of what’s most useful clinically. There are other analytes in the urine that are underappreciated.

Keri, what are your reflections on this discussion? Three or four percent sounds like a great attainment in urinalysis. There are many laboratories that would not be able to achieve such a low rate of manual review.
Dr. Donaldson (Solvd Health): The whole point of decreasing the percent of samples when there is need for a manual review is it gives folks who may or may not be skilled in the art of urinalysis additional time to focus on the samples that need the most attention, and I think these newer instruments make the lower review rates attainable.

What’s also inherent in that number is the majority of the samples are classified appropriately and quickly, and meaningful results are returned to the clinician. The fact that that number is coming down and is reproducible and able to be put in other people’s hands, from large centralized laboratories to smaller satellite laboratories, and standardized or harmonized across different sites, is a great thing.

To echo what Matt and Jason said, as this standardized data becomes more recognized, you will have additional data points, whether those are prognostic data points in terms of the presence or absence of different types of diseases and if that would change patient care, or flow cytometric results. You can talk about what types of bacteria are present and maybe even about early decisions on antibiotics. That’s the bleeding edge, if you will, of urinalysis—if you can get a urine result quickly before a culture result or a susceptibility result comes back. If you can have information sooner and make a better decision, then it can better impact patient care.

How does your expertise in urinalysis and developing advanced analyzers relate to the work you’re doing now as CEO of Solvd Health, which develops technologies that identify risk of disease?
Dr. Donaldson (Solvd Health): It’s all how you think about using data being generated from diagnostic tests to drive clinical decisions and eventually enable better patient care. From a method perspective, I’m an agnostic; I don’t care where the data comes from or how it’s generated. In urinalysis we’re talking about different types of information, whether it’s visual, image processing, or flow cytometric analysis.

With the work now at Solvd Health, the data source has changed. Instead of looking at flow cytometric analysis, we may be processing data from metagenomic analysis in bacterial colonies from the colon to detect early signs of lesions that could become cancerous. These are still data points. There may be more of them, and one could argue they may be more complex, but we process that data and look at it the same way, and at the end of the day there’s a patient and you’re trying to inform decisions around that patient’s care. As an example, we are part of a consortium using luminal microbiome data to improve the sensitivity of detecting advanced adenomas from 42 percent using tests that use traditional data modeling to more than 90 percent.

Some of our other testing identifies increased risk of developing opioid addiction for prescribing decisions.

Talk about urine as a specimen as it enables some of that work—is it a good or a bad specimen?
Dr. Donaldson (Solvd Health): It’s one of the oldest specimens for diagnostic testing. The information the new analyzers are producing allows us to look deeper in urine for additional data points. The most interesting from my perspective would be trying to make decisions—once the urine is positive or negative—on therapeutic selection, in particular with multidrug-resistant bacteria and decreasing the broader coverage as soon as possible, which has shown to be advantageous. Analyzers are getting closer to having that information available.

One of the most common reasons a person is put on antibiotics is for urinary tract infections. And the difference in days between a urine and culture result is maybe two to three. You take a two- to three-day difference in terms of antibiotic prescription or narrowing it from broad to narrow spectrum, that’s a lot of different antibiotics being given to people when you could narrow the resistance profile pretty quickly.

People at Beckman Coulter and Sysmex, to my knowledge, are moving down that same track of saying we can get to earlier detection and stewardship of antibiotics.
Dr. Donaldson (Solvd Health): Quite a few people I know are looking at it. I would encourage it.

Megan, does this sound intriguing as something you look to have on hand in the future at your laboratory?
Dr. Nakashima (Cleveland Clinic): From a systems perspective, yes. I am not involved in microbiology, but all the points Dr. Donaldson spoke to are what we strive toward as a health care system.

Megan, in our discussion last year you said tube manufacturers could do an enormous service if there were preservatives in all urine tubes. Matt, you had comments about how difficult that is. Like a lot of great ideas, the execution is not simple. Has anything come down the track to make it easier to provide preservatives?
Dr. Rhyner (Beckman Coulter): It continues to be a challenge. First, there are not many preservative tubes on the market. There are stringent CLSI guidelines on running urine samples within a specified time frame unless it’s in a preservative tube. There are questions, too, on the chemistry side more so than with microscopy about what effect preservatives might have, especially with semiquantitative chemistry strips. It’s a continuing topic of conversation.

We have preservative tube claims with the Arkray system, but it is something we will have to address as we look into future developments of new chemistry systems. Understanding better the interaction of the chemical preservatives with the color-changing pad on the strip is an area that merits investigation.