Science

Performance Evaluation and Comparison of the

Fully Automated Urinalysis Analyzers UX-2000
and Cobas 6500

Downloaded from https://academic.oup.com/labmed/article/47/2/124/2937881 by guest on 01 December 2022

Bongkot Wesarachkitti, BSc, Varanya Khejonnit, BSc, Busadee Pratumvinit, MD,
Kanit Reesukumal, MD, Suriya Meepanya, BPH, Chanutchaya Pattanavin, BSc,
Preechaya Wongkrajang, MD*
Laboratory Medicine 47:2:124-133

DOI: 10.1093/labmed/lmw002

ABSTRACT demonstrated a higher level of agreement for red blood cells (Cobas
6500: R ¼ 0.94; UX-2000: R ¼ 0.78) and white blood cells (Cobas
Objective: To evaluate and compare the performances of the automated 6500: R ¼ 0.95; UX-2000: R ¼ 0.85). The UX-2000 demonstrated
urinalysis devices UX-2000 and Cobas 6500. higher sensitivity for small round cells, hyaline casts, pathological casts,
and bacteria. The median turnaround time was 1.5 minutes and
Method: A total of 258 urine specimens were collected from the 8.5 minutes for the Cobas 6500 and UX-2000, respectively.
routine specimen workload. We analyzed all specimens on both
automated instruments and recorded the turnaround time from each Conclusions: The 2 devices showed similar performance in technical
method. Physical, chemical, and sedimentary urine components were evaluation; they each reduce workload and increase time saving.
compared between the automated and the manual method for each However, manual examination by technicians is recommended for
analyzer. pathological specimens.

Results: The correlation of urine physical/chemical properties between Keywords: automated urine analyzer, urinalysis, Cobas 6500, Sysmex
the 2 instruments was excellent. The Cobas 6500 instrument UX-2000, instrumentation, manual urinalysis

Urinalysis is one of the most common screening tests in eliminate interobserver/intraobserver variation and save labor
clinical practice. In addition to evaluating the condition of the and time, making these analyzers an attractive alternative in
kidney and genitourinary systems, urinalysis can also identify a high-volume laboratory setting.
problems in other organs/systems (eg, liver, muscle).
Generally, urinalysis is composed of 3 component parts: Most analysis operations in the physical and chemical
physical, chemical, and microscopic examination.1-3 components of urinalysis are based on similar principles, such
as the refractometry/refractive index method for specific gravity
Many manufacturers have developed automated urine in the physical component and reflectance spectroscopy for
analyzers that integrate and perform all 3 urinalysis analytes in the chemical component. For the microscopic-
components. The use of automated urine analyzers can examination component, 2 technologies are available for
analyzing sediment in urine, including a built-in camera system
to take pictures of specimen and flow cytometry.4-6
Abbreviations
RBCs, red blood cells; WBCs, white blood cells; CV, coefficient of vari- Recently, Sysmex Corporation developed the UX-2000, a
ation; ICC, intraclass correlation coefficient; PPV, positive predictive fully automated urine analyzer that can evaluate all 3
value; NPV, negative predictive value
analysis components in a single efficient device. For
Department of Clinical Pathology, Faculty of Medicine, Siriraj Hospital, sediment analysis, the UX-2000 uses the fluorescence
Mahidol University, Bangkok, Thailand flow cytometry method. Roche Diagnostics also recently
*To whom correspondence should be addressed. developed and introduced a fully automated urine
[email protected] analyzer, the Cobas 6500. In contrast to the UX-2000,

C American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: [email protected]
V 124
 Science

Table 1. Characteristics of the UX-2000 and Cobas 6500 Analyzersa

General Characteristic UX-2000 Cobas 6500
Specimen application Pipetted Pipetted
Sample throughput per hour 200 (chemical part only) 240 (Cobas u 601 only)
100 (flow cytometry only) 116 (Cobas u 701 only)
150 (chemical part þ flow cytometry)
Specimen consumption 2.2 mL 2.3 mL

Downloaded from https://academic.oup.com/labmed/article/47/2/124/2937881 by guest on 01 December 2022

Required specimen volume 5 mL 2.8 mL
Data memory (tests) 10,000 10,000
Physical dimensions Width: 80 cm Width: 179 cm
Depth: 72 cm Depth: 53 cm
Height: 72 cm Height: 64.4 cm
Physical and Chemical Parts
Turbidity method Light-scattering Turbidimeter
Specific gravity method Refractometry (automatic glucose and Refractometry (automatic temperature
protein compensation) compensation)
Wave lengths used 430, 500, 565, 635, 760 nm 465, 528, 560, 615 nm

Microscopic Components
Specimen application Flow system Cuvette
Centrifuge No 2000 rpm for 10 seconds
Principle of analysis Fluorescence flow cytometry Digital imaging and particle recognition software
Stain Yes (fluorescence) No
Image None Monochrome
Output of images No images available Images available
a
The UX-2000 is manufactured by Sysmex Corporation; the Cobas 6500 by F. Hoffmann-La Roche Ltd.

the Cobas 6500 uses digital imaging for microscopic antiseptic-free containers for urine collection. We analyzed
examination. all specimens within 2 hours after our laboratory received
them. Each urine specimen was divided into 3 aliquots. The
The objective of this study was to evaluate performance and first and second parts were analyzed by one of the 2
time consumed by testing in performing a comparison automated analyzers, without centrifugation. The third
between the UX-2000 and the Cobas 6500 automated part was analyzed via the manual microscopic method.
urinalysis systems. Our evaluation included the physical, Each urine specimen was examined by 1 experienced
chemical, and microscopic examination component technician (VK).
processes.

Automated Urine Analyzers

Materials and Methods UX-2000

Urine Specimens The UX-2000 has 2 component analyzers in a single

platform, namely, a chemical component for analyzing the
We performed this study at the central laboratory of the physical and chemical parts of urine and a flow cytometry
Department of Clinical Pathology, Faculty of Medicine, component for microscopic examination of sediments.
Siriraj Hospital, Mahidol University, Bangkok, Thailand, Characteristics of the UX-2000 are described in Table 1.
between March and May 2015. The 258 total urine
specimens included in this study were excess, unidentified Analysis parameters of the physical and chemical parts of
specimens collected from the inpatient and outpatient the UX-2000 include specific gravity, turbidity, color,
departments. As such, this study was exempted from the glucose, protein, bilirubin, urobilinogen, pH, occult blood,
Siriraj Institutional Review Board research study approval ketone, nitrite, leukocyte esterase, creatinine, protein/
process. The laboratory had used clean, preservative-free, creatinine ratio, albumin, and albumin/creatinine ratio.

www.labmedicine.com Lab Medicine 2016;47:2;124–133 125

DOI: 10.1093/labmed/lmw002
Science

For the microscopic examination component, measurement and squamous epithelial cells, at a magnification of 400, in
of quantifiable components by flow cytometry principle is 10 small squares. Casts were evaluated using the low power
performed for red blood cells (RBCs), white blood cells field, at 100 magnification. The number of cells was
(WBCs), hyaline casts, bacteria, and epithelial cells. Other calculated according to the following equation;9
nonquantifiable components, such as crystals, yeast-like
cells, small round cells (including renal tubular cells, n  V pellet
Cell  106 =L ¼
transitional epithelial cells, and oval fat bodies), V chamber  V tube

Downloaded from https://academic.oup.com/labmed/article/47/2/124/2937881 by guest on 01 December 2022

spermatozoa, and pathological casts are detected and n ¼ number of cells counted in 10 small squares
flagged (thresholds defined by the user) for operator review V pellet ¼ volume of pellet after centrifugation
via manual examination because this analyzer cannot V chamber ¼ volume of 10 small squares
differentiate between those types of sediment.7
V tube ¼ total volume of urine in test tube

Cobas 6500

This analyzer consists of 2 component modules, namely, the

Evaluation Protocols and
Cobas u 601 for analyzing the physical and chemical specimen Analysis of Results
components and the Cobas u 701 for microscopic analysis.
Characteristics of the Cobas 6500 are shown in Table 1. Physical and Chemical Components

The Cobas u 601 can evaluate the following urine specimen For the physical component of urinalysis, we compared the
components: specific gravity, turbidity, color, glucose, specific gravity result from each of the 2 instruments. Specific
protein, bilirubin, urobilinogen, pH, occult blood, ketone, gravity was statistically evaluated by regression analysis and
nitrite, and leukocyte esterase. coefficient correlation (R). For the chemical component, we
evaluated pH, glucose, protein, urobilinogen, bilirubin, ketone,
When using the Cobas u 701, urine specimen is pipetted into blood, leukocyte esterase, and nitrites. Results from the
a special cuvette. Then, the cuvettes are centrifuged at chemical part were considered to be concordant if their results
2000 rpm for 10 seconds. A microscopic camera takes 15 were within 1 grading difference. Pairwise concordance rate
microscopic images that are then analyzed via particle between the 2 instruments was defined by the percent of
recognition software for the following parameters: RBCs, results within 61 grading from the best-fit line.5
WBCs, casts, bacteria, squamous epithelial cells, crystals,
yeasts, small round cells or nonsquamous epithelial cells,
spermatozoa, and pathologic casts.8 We calibrated the UX- Microscopic Evaluation Component
2000 and Cobas 6500 instrument modules and ensured that
they passed internal quality control procedures before Precision Test
analyzing specimens for this study.
To test for consistency of results, we analyzed 2-level urine
particle quality control specimens, including RBCs and
Manual Microscopic Method WBCs, 20 times within a single day for within-run
reproducibility and once per day in 20 separate days for
We examined all specimens via manual microscopy. We between-run precision. The precision of each measurement
centrifuged 10 mL of each urine specimen in a conical tube method was determined by coefficient of variation (CV).
at 2000 rpm for 5 minutes and discarded 9 mL of
supernatant. The remaining 1 mL of urine specimen material
was resuspended and pipetted onto a Vetriplast slide Linearity Test
(Vacutest Kima) and examined under a CX31 upright
microscope (Olympus Corporation). To estimate linearity (the ability of the instrument to count
urine particles in various specimen concentrations,
For counting cells in the chamber, we selected the middle compared with actual concentrations), we analyzed 2 urine
section in the grid and counted cells, such as RBCs, WBCs, specimens, the first with a high RBC count and the second

126 Lab Medicine 2016;47:2;124–133 www.labmedicine.com

126 DOI: 10.1093/labmed/lmw002
 Science

with high WBC counts. For linearity studies, a high

Table 2. Correlation Represented as
concentration of particles (abnormal) was produced by
Concordance Rate (%) and Concordance Rate
centrifugation and then diluted with normal urine to obtain a Within 6 1 Grading Difference (%) of Urinalysis
series of 5 concentrations. We analyzed each concentration Results Between the UX-2000 and Cobas 6500a
level using both automated urine analyzers and performed Parameter Concordance Concordance Rate Within
each test in duplicate. Linearity was determined by Rate (%) 6 1 Grading Difference (%)
regression analysis and coefficient correlation (R). Glucose 97 100

Downloaded from https://academic.oup.com/labmed/article/47/2/124/2937881 by guest on 01 December 2022

Protein 88 100
Urobilinogen 92 99
Bilirubin 88 98
Sediment Comparison pH 41 98
Ketone 96 100
Blood 65 96
We divided the sediment results from both automated Nitrite 94 94
analyzers and the manual methods used into 3 categories for Leukocyte esterase 76 100
evaluation. First, the data for RBCs and WBCs were a
The UX-2000 is manufactured by Sysmex Corporation; the Cobas 6500 by F.
converted into particles per mL. Agreements between the 3 Hoffmann-La Roche Ltd.

methods were assessed via coefficient correlation (R) and

Bland-Altman plotting.10 We used the intraclass correlation Data Analysis
coefficient (ICC) to test for agreement between methods,
with P <.05 considered to be statistically significant. For We performed statistical analysis using PASW Statistics for
interpretation of ICC values, we applied the Landis and Koch Windows, version 18.0 (SPSS, Inc), and Microsoft Excel
criteria, as follows: ICC of 0.00 to 0.20, 0.21 to 0.40, 0.41 to (Microsoft Corporation). For the Cobas 6500, we derived data
0.60, 0.61 to 0.80, and greater than 0.80, for slight results for statistical analysis of precision and linearity studies
agreement, fair agreement, moderate agreement, substantial from original data only. For sediment comparison against
agreement, and almost perfect agreement, respectively.11 manual microscopy assay results, 1 qualified staff member
Bongkot Wesarachkitti to reclassified digital images to show
Second, we categorized data for squamous epithelial cells, maximum obtainable performance. P <.05 was regarded as
small round cells, hyaline casts, pathological casts, and statistically significant.
crystals as being negative or positive. If a crystal was found
to be positive, it may have been identified according to its
specific urinary crystal character. We calculated specificity,
sensitivity, positive predictive value (PPV), and negative
Results
predictive value (NPV) for these data using the criterion
standard method of manual microscopy. Physical and Chemical Components

Third, to compare performance regarding identification and The coefficient correlation and linear regression of specific
measurement of bacteria for these 3 methods, results were gravity from the UX-2000 and the Cobas 6500 automated
considered concordant if they were within 1 grading urine analyzers were 0.97 and y ¼ 0.843x þ 0.160,
difference. We considered the pairwise concordance rate respectively. The pairwise table of the chemical component,
between automated analyzers and the manual method to be which demonstrated the concordance of the 2 systems, is
the reference method.2 summarized in Table 2.

Turnaround Time Microscopic Component

The amount of turnaround time in analyzing each specimen Precision and Linearity Testing
was recorded as Second. Results reported as
mean6 standard deviation data were normally distributed Within-run and between-run CVs of RBCs and WBCs for both
and median6 standard deviation if data were not normally instruments are presented in Table 3. We performed linearity
distributed. testing by analyzing 5 dilutions (5:0, 4:1, 3:2, 2:3, 1:4) of 2 urine

www.labmedicine.com Lab Medicine 2016;47:2;124–133 127

DOI: 10.1093/labmed/lmw002
Science

Table 3. Coefficients of Variation of Microscopic Analysis from UX-2000 and Cobas 6500a,b
Within Precision Between Precision

Level 1 (Low) Level 2 (High) Level 1 (Low) Level 2 (High)

Analyzer Parameter (cells/mL) mean 6 SD CV (%) mean 6 SD CV (%) mean 6 SD CV (%) mean 6 SD CV (%)
UX-2000 RBCs 38.80 6 2.44 6.3 181.75 6 4.68 2.6 41.99 6 3.99 9.5 191.26 6 10.47 5.5
WBCs 40.12 6 1.68 4.2 775.28 6 10.31 1.3 42.35 6 2.34 5.5 777.27 6 30.42 3.9

Downloaded from https://academic.oup.com/labmed/article/47/2/124/2937881 by guest on 01 December 2022

Cobas 6500 RBCs 0.0 (*) * 925.52 6 61.79 6.7 1.32 6 4.71 357 981.95 6 118.02 12
WBCs 0.0 (*) * 170.58 6 14.72 8.6 0.17 6 0.52 314.6 168.47 6 14.25 8.5
RBCs, red blood cells; WBCs, white blood cells
a
Indicates that SD and coefficient of variance (CV) cannot be calculated because the mean value of RBC and WBC results was 0 cells per mL.
b
The UX-2000 is manufactured by Sysmex Corporation; the Cobas 6500 by F. Hoffmann-La Roche Ltd.

specimens on both automated urine analyzers. One specimen Bacteria counts showed significant variation among the 3
had a high RBC count; the other had a high WBC count. methods (Figure 3). The UX-2000 vs manual microscopic
examination demonstrated stronger concordance (84%) than
For RBC analysis using 5 dilutions, cell concentrations the Cobas 6500 vs manual microscopic examination (71%).
ranged from 8964.6 cells per mL in undiluted urine to 1747.2
cells per mL in urine with 1:4 dilution for the UX-2000; and
from 2241.6 cells per mL in undiluted urine to 126.4 cells per Turnaround Time
mL in urine with 1:4 dilution for the Cobas 6500. For WBC
analysis in 5 dilutions, concentrations ranged from 12,712.2 The median turnaround time for processing of specimen on
cells per mL in undiluted urine to 2783.1 cells per mL in urine the UX-2000 assay was 500 6 215.3 seconds. The median
with 1:4 dilution for the UX-2000; and from 703.5 cells per mL processing turnaround time for the Cobas 6500 was
in undiluted urine to 135.9 cells per mL in urine with 1:4 93.5 6 29.7 seconds.
dilution for the Cobas 6500. The correlation coefficients (R)
for the UX-2000 and the Cobas 6500 results are shown in
Figure 1.
Discussion
The automated urinalysis method improves reproducibility. In
Sediment Comparison addition, it improves efficiency by increasing productivity/
throughput and reducing labor and the time needed to
We also examined the relationships between the 2 devices process urine specimens.
and manual assay for sedimentary analyses (Table 4). Bland-
Altman plots for all systems are shown in Figure 2. The plots In this study, we compared the performance of 2 fully
describe a tendency toward lower results for both automated automated urine analyzers. Many previous reports have also
analyzers, relative to the manual method in increasing RBC evaluated automated urine instruments, but our study is the
and WBC counts. first, to our knowledge, to compare fully automated 3-part
(physical, chemical, and sediment) urine analyzers and to
Results from the performance of cell and formed element evaluate the time consumed in specimen processing.
measurement by UX-2000 vs manual assay and Cobas 6500
vs manual assay are shown in Table 5. The Cobas 6500 The specific gravity measured by the 2 devices had excellent
demonstrated higher sensitivity and specificity than the UX- correlation. The advantages of the UX-2000 specific gravity
2000 in detection of yeast and squamous epithelial cells, assay include measurement by the refractometry method
whereas the UX-2000 more accurately identified small round and automatic correction using glucose and protein
cells, hyaline casts, and pathological casts. For crystals, the concentration values. We draw attention to this finding in
UX-2000 had lower sensitivity overall but higher specificity particular because high protein and glucose levels can
than the Cobas 6500. elevate specific gravity result when measured via

128 Lab Medicine 2016;47:2;124–133 www.labmedicine.com

128 DOI: 10.1093/labmed/lmw002
 Science

A B
10000 15000

WBC Count Measured (cells/µl)

RBC Count Measured (cells/µl)

8000 20000

6000 9000

4000 6000

Downloaded from https://academic.oup.com/labmed/article/47/2/124/2937881 by guest on 01 December 2022

2000 3000
y = 0.996x + 50.735 y = 0.986x + 525.855
R = 0.999 R = 0.995

0 0
0 5000 10000 0 3000 6000 9000 12000 15000
Calculated RBC Count (cells/µl) Calculated WBC Count (cells/µl)
C D
800

WBC Count Measured (cells/µl)

RBC Count Measured (cells/µl)

200
600
1500

400
1000

200
500
y = 1.206x - 490.940 y = 0.802x + 138.5
R = 0.997 R = 0.995

0 0
0 500 1000 1500 5000 2500 0 200 400 600
Calculated RBC Count (cells/µl) Calculated WBC Count (cells/µl)

Figure 1
Linearity results for red blood cell (RBC) and white blood cell (WBC) counts in specimens tested via the UX-2000 (Sysmex Corporation) and the
Cobas 6500 (F. Hoffmann-La Roche, Ltd.) instruments. A, RBC count as determined via UX-2000. B, WBC count as determined via UX-2000.
C, RBC count via Cobas 6500. D, WBC count via Cobas 6500. RBC indicates red blood cell; WBC indicates white blood cell.

Table 4. Correlation Coefficients Between the UX-2000 and Manual Microscopy and the Cobas 6500
and Manual Microscopy for Red Blood Cells and White Blood Cellsa
Variable Correlation Intraclass P Value
Coefficient (R) Correlation
Red blood cells UX-2000 vs manual 0.78 0.60 <.01
Cobas 6500 vs manual 0.94 0.87 <.01
White blood cells UX-2000 vs manual 0.85 0.56 <.01
Cobas 6500 vs manual 0.95 0.91 <.01
a
The UX-2000 is manufactured by Sysmex Corporation; the Cobas 6500 by F. Hoffmann-La Roche Ltd.

refractometry. The correction involves subtracting 0.003 for For the sediment component of automated urinalysis,
each gram per deciliter of protein and 0.004 for each gram between- and within-precision values for both methods were
per deciliter of glucose.2,12,13 Our performance evaluation of higher in specimens with fewer cells (control level 1). The
chemical component analysis for both instruments also precision data produced by the UX-2000 in this study were
yielded good correlation. similar to the precision data produced by the UF-1000i

www.labmedicine.com Lab Medicine 2016;47:2;124–133 129

DOI: 10.1093/labmed/lmw002
Science

Table 5. Diagnostic Accuracy of Sediment Analysis, Compared With Manual Microscopy

Variablea Sensitivity (%) Specificity (%) Positive Predictive Negative Predictive
Value (%) Value (%)
Yeasts
UX-2000 11.5 93.5 16.7 90.4
Cobas 6500 57.1 98.8 72.7 97.6
Squamous epithelial cells

Downloaded from https://academic.oup.com/labmed/article/47/2/124/2937881 by guest on 01 December 2022

UX-2000 18.2 86.4 11.1 91.9
Cobas 6500 36.4 94.1 36.4 94.1
Small round cells
UX-2000 57.7 86.6 32.6 94.8
Cobas 6500 11.5 100.0 100.0 91.0
Hyaline casts
UX-2000 50.0 85.9 12.5 97.7
Cobas 6500 10.0 98.8 25.0 96.5
Pathological casts
UX-2000 45.1 93.7 63.9 87.4
Cobas 6500 39.2 98.1 83.3 86.8
Crystals
UX-2000 32.7 99.0 90.0 84.5
Cobas 6500 67.3 98.5 92.5 91.7
a
The UX-2000 is manufactured by Sysmex Corporation; the Cobas 6500 by F. Hoffmann-La Roche Ltd.

(Sysmex Corporation), as reported in a previous study.14 The study, we had a high proportion of abnormal urine
CV% from the between-run precision of the level 1 control for specimens, with a rate of positive results of sediment
the Cobas 6500 was very high (>300%) because the results analysis greater than 80%.
from day 1 to day 16 had no RBCs or WBCs present, but the
last 4 specimens (days 17 to 20) yielded RBC and WBC Specimens that contain higher microorganism
counts ranging from 1.32 through 21.12 cells per lL. This concentrations (eg, bacteria, yeast) have higher incidence of
situation may result from high concentration of particle error in RBC detection. In addition, Jiang et al report that low
material at the bottom of each specimen container that RBC concentration tended to yield false results in UF-1000i
occurs due to the low volume of control solution. Linearity of automated analysis. Moreover, high amounts of small round
RBCs and WBCs was excellent for both instruments. cells can interfere with detection of WBCs. Agreement
between the results of Cobas 6500 analysis and manual
In contrast to the findings of a previous study,14-15 the counting of RBCs and WBCs was excellent. This finding may
correlation of RBCs and WBCs as measured by the UX-2000 be attributable to the fact that the Cobas 6500 and the
in this study, which uses the same technology as the manual method both use imaging for measurement. The
Sysmex UF-1000i, demonstrated only substantial agreement Cobas 6500 and the UriSed (77 Elektronika Kft) use similar
with the manual method. Results from a study by Jiang et al technology. Several studies16-19 reported that the Urised
showed very good correlation for UF-1000i compared with instrument was highly reliable in measurement of RBCs and
the manual method for RBCs (R ¼ 0.96) and WBCs (R ¼ WBCs.
0.98).14 Manoni et al also found very satisfactory correlation
between the UF-1000i and microscopy: for RBCs, R ¼ 0.98; For small round cells and hyaline and pathological casts, the
for WBCs, R ¼1.00.15 Results from the microscopic method UX-2000 demonstrated greater sensitivity than the Cobas
in this study showed higher cell counts than results from the 6500, whereas the Cobas 6500 showed greater sensitivity for
UX-2000 instrument, as shown via Bland-Altman plotting. squamous epithelial cells, crystals, and yeasts. We point out
This finding may be explained by differences in the that the UX-2000 cannot distinguish small round cells,
equipment used in the manual method. For example, in the pathological casts, and crystals, which are clinically significant
Jiang et al study, the researchers used microscope slides entities in the diagnosis of renal disease. A positive result in
and cover glass, and in contrast, in the Manoni et al study, any of these 3 factor categories generated by the UX-2000
researchers used uncentrifuged specimens. Moreover, in our requires use of the microscopic method for confirmation and

130 Lab Medicine 2016;47:2;124–133 www.labmedicine.com

130 DOI: 10.1093/labmed/lmw002
 Science

Downloaded from https://academic.oup.com/labmed/article/47/2/124/2937881 by guest on 01 December 2022

Figure 2
Bland-Altman plots for red blood cell (RBC) and white blood cell (WBC) counts in specimens tested via the UX-2000 (Sysmex Corporation) and
the Cobas 6500 (F. Hoffmann-La Roche, Ltd.) instruments and in each instrument vs manual assays. A, RBC count via UX-2000 vs Cobas
6500. B, RBC count via UX-2000 vs manual assays. C, RBC count via Cobas 6500 vs manual assays. D, WBC count via UX-2000 vs Cobas
6500. E, WBC count via UX-2000 vs manual assays. F, WBC count via Cobas 6500 vs manual assays.

differentiation. In addition, the study from Sharda et al20 Our institution, Siriraj Hospital, is the largest comprehensive
showed that the manual microscopic examination of urine hospital in Thailand and the leading national referral center,
sediments in patients with acute kidney disease should be with 2600 beds for inpatients and with outpatient traffic that
performed in every case after using automated microscopy. exceeds 10,000 patients per day. Approximately 600
Bacteria counts from the UX-2000 showed stronger specimens are routinely submitted to our department for
correlation to the microscopic method than the Cobas 6500. urine examination every day. In 2014, the Department of
Clinical Pathology at our hospital changed its urinalysis
Regarding the time consumed by automated analyzers, the process. In our laboratory, we now use the fully automated
UX-2000 took approximately 4 times longer than the Cobas UX-2000 urine analyzer and we have established optimal
6500 to process a specimen. Also, approximately 80% of protocols for microscopic review after use of the UX-
specimens analyzed by the UX-2000 and found to have 2000.21 Although the combination of the UX-2000
abnormal results should have those results confirmed via the instrument and the manual microscopic method yield
manual microscopic method. Processes associated with the optimal results, our technicians perform microscopic review
manual microscopic method, such as centrifugation, in approximately 50% to 60% of cases. As a result, urinalysis
discarding specimen material, specimen slide set-up, and remains a high-volume, labor-intensive responsibility in our
manual microscopic review require more time and labor than laboratory.
the automated method. By comparison, only 10% of abnormal
specimens analyzed by the Cobas 6500 need to be further The laboratory workflows for the UX-2000 and the Cobas
analyzed via the conventional microscopic method. 6500 instruments are different, even when abnormal urine

www.labmedicine.com Lab Medicine 2016;47:2;124–133 131

DOI: 10.1093/labmed/lmw002
Science

A B
Manual Method Manual Method

4+ 2 0 0 2 2 9 22 4+ 1 0 0 1 0 2 15

3+ 0 0 1 6 2 3 1 3+ 0 0 0 0 1 6 5

2+ 0 0 2 4 1 3 0 2+ 1 0 0 3 3 3 2

1+ 0 5 11 4 3 1 0 1+ 1 0 10 10 3 4 0

Downloaded from https://academic.oup.com/labmed/article/47/2/124/2937881 by guest on 01 December 2022

FEW 10 16 12 2 2 0 0 FEW 1 9 6 5 1 1 2

RARE 0 0 0 0 0 0 0 RARE 21 38 25 4 2 2 0

NEG 45 45 15 8 1 2 1 NEG 32 19 15 1 1 0 0

NEG RARE FEW 1+ 2+ 3+ 4+ NEG RARE FEW 1+ 2+ 3+ 4+

Concordance rate 34% Concordance rate 43%
Concordance rate 71% Concordance rate
within +1 grading within +1 grading 84%

Number of samples: 258 Number of samples: 258

Figure 3
Comparison of pairwise bacteria between the UX-2000 (Sysmex Corporation) and manual microscopy and the Cobas 6500 (F. Hoffman-La
Roche Ltd.) and manual microscopy. A, UX-2000; B, Cobas 6500. The shaded area ( ) represents number of cases within 1 grade difference;
( ), the same-grade agreement; NEG, negative.

Table 6. Summary of Advantages and Disadvantages of the UX-2000 and Cobas 6500a
UX-2000 Cobas 6500
Advantage Less space needed Less volume required
Uses uncentrifuged specimen No reagents required
More reliable for specific gravity in specimens that Images available for review
contain a large amount of glucose or protein Higher sensitivity for red blood cells, white blood cells,
Higher sensitivity for small round cells, casts, and bacteria yeasts, crystals, and squamous epithelial cells
Disadvantage Reagent required (fluorescent) Less reliable for specimens that contain a large amount
Higher turnaround time of glucose or protein
Flagged results need to be confirmed by manual Ultracentrifugation of sample can cause sediment loss
microscopy (50%-60%)
a
The UX-2000 is manufactured by Sysmex Corporation; the Cobas 6500 by F. Hoffmann-La Roche Ltd.

results require confirmation by staff. In the UX-2000, the quite different. For the UX-2000, the rate of manual method
computer checks an abnormal urine-specimen result to is about 50% to 60%, in contrast with a rate of 10% to 20% for
determine whether it requires further review. If the the Cobas 6500. Hence, labor needs are less, and
specimen requires review via the conventional method, staff turnaround time is significantly reduced.
members will centrifuge it and review the centrifuged Based on our findings, the UX-2000 and the Cobas 6500
specimen via microscopy. The Cobas 6500 is easier and instruments demonstrated many advantages and drawbacks
more convenient to use than the UX-2000, given that after a (Table 6). The limitations of this study were the small sample
urine specimen is processed, any portion that tested as size; the limited diversity of the specimens; and the small
being abnormal can be reviewed by evaluating its image in number of pathological urine specimens, especially for casts
the computer (except for turbid or mucous specimens, which and yeasts. Also, we did not perform any clinical follow-up or
need to be manual reviewed via microscope). So, the rate of gather any information about the clinical consequences of
conventional manual method between the 2 analyzers is urine microscopy results.

132 Lab Medicine 2016;47:2;124–133 www.labmedicine.com

132 DOI: 10.1093/labmed/lmw002
 Science

In conclusion, the UX-2000 and Cobas 6500 devices showed 6. Chien TI, Kao JT, Liu HL, et al. Urine sediment examination: a comparison
of automated urinalysis systems and manual microscopy. Clin Chim Acta.
similar performance in physical/chemical characteristics and 2007;384:28–34.
reliability in measurement of certain urinary parameters, such 7. Fully automated integrated urine analyzer UX-2000 instructions for use.
as RBCs and WBCs for the Cobas 6500 and small round Sysmex Corporation; 2010-2011.
R
V
cells, hyaline casts, and pathological casts for the UX-2000. 8. Cobas 6500 urine analyzer series, version 1.0.0, Operator’s Manual. F.
Hoffman-La Roche, Ltd.;2014-05.
Both machines can reduce workload, increase time savings,
9. Ottiger C, Huber AR. Quantitative urine particle analysis: integrative ap-
and decrease human error in preparations for microscopic proach for the optimal combination of automation with UF-100 and

Downloaded from https://academic.oup.com/labmed/article/47/2/124/2937881 by guest on 01 December 2022

analysis, such as centrifugation. However, examination by microscopic review with KOVA cell chamber. Clin Chem. 2003;
49:617–623.
skilled technicians is recommended for pathological urine
10. Bland JM, Altman DG. Statistical methods for assessing agreement
specimens. LM between two methods of clinical measurement. Lancet. 1986;8:307–310.
11. Landis JR, Koch GG. The measurement of observer agreement for cat-
egorical data. Biometrics. 1977;33:159–174.
Acknowledgments 12. Chadha V, Garg U, Alon US. Measurement of urinary concentration: a crit-
ical appraisal of methodologies. Pediatr Nephrol. 2001;16:374–382.

Research authors Wongkrajang, Pratumvinit, and 13. Strasinger SK, Di Lorenzo MS. Physical examination. In: SK Strasinger,
MS Di Lorenzo, eds. Urinalysis and Body Fluids. 6th ed. Philadelphia: F.
Reesukumal were supported by a Chalermphrakiat Grant A. Davis Company, 2014;59–70.
from the Faculty of Medicine Siriraj Hospital, Mahidol 14. Jiang T, Chen P, Ouyang J, Zhang S, Cai D. Urine particles analysis: per-
University, Bangkok, Thailand. We thank Julaporn Pooliam, formance evaluation of Sysmex UF-1000i and comparison among urine
flow cytometer, dipstick, and visual microscopic examination. Scand J
MSc, for her assistance with statistical analysis. Also, we Clin Lab Invest. 2011;71:30–37.
thank Roche Diagnostics for providing the Cobas 6500 and 15. Manoni F, Tinello A, Fornasiero L, et al. Urine particle evaluation: a com-
all supplies that we used in the present study. parison between the UF-1000i and quantitative microscopy. Clin Chem
Lab Med. 2010;48:1107–1111.
16. Zaman Z, Fogazzi GB, Garigali G, Croci MD, Bayer G, Kranicz T. Urine
sediment analysis: Analytical and diagnostic performance of sediMAX – a
References new automated micro scopy image-based urine sediment analyser. Clin
Chim Acta. 2010; 411:147–154.
1. European Confederation of Laboratory Medicine. European urinalysis 17. Yu lu O. Comparison of fully automated
€ksel H, Kiliç E, Ekinci A, Evliyaog
guidelines. Scand J Clin Lab Invest Suppl. 2000;231:1–96. urine sediment analyzers H800-FUS100 and LabUMat-UriSed with man-
ual microscopy. J Clin Lab Anal. 2013;27:312–316.
2. Rabinovich A, Arzoumanian L, Curcio K, Dougherty B, Abdel-Baset H.
Urinalysis Approved Guidelines. 3rd ed. Clinical and Laboratory 18. Ma J, Wang C, Yue J, et al. Clinical laboratory urine analysis: comparison
Standards Institute (CLSI) GP16-A3. 2009;29:1–33. of the UriSed automated microscopic analyzer and the manual micros-
copy. Clin Lab. 2013;59:1297–1303.
3. McPherson RA, Ben-Ezra J. Basic examination of urine. In: RA
McPherson, MR Pincus, eds. Henry’s Clinical Diagnosis and 19. Bottini PV, Martinez MH, Garlipp CR. Urinalysis: comparison between
Management by Laboratory Methods. 22nd ed. Philadelphia: Elsevier microscopic analysis and a new automated microscopy image-based
Saunders, 2011:445–479. urine sediment instrument. Clin Lab. 2014;60:693–697.
4. National Health Service (NHS) Purchasing and Supply Agency: Centre for 20. Sharda N, Bakhtar O, Thajudeen B, Meister E, Szerlip H. Manual urine mi-
Evidence-Based Purchasing (CEP). CEP evidence review: automated croscopy versus automated urine analyzer microscopy in patients with
urine screening systems (CEP 10030); 2010. acute kidney injury. Lab Medicine. 2014;45(4):e152–155.
5. Chien T-I, Lu J-Y, Kao J-T, et al. Comparison of three automated urinaly- 21. Khejonnit V, Pratumvinit B, Reesukumal K, Meepanya S, Pattanavin C,
sis systems—Bayer Clinitek Atlas, Roche Urisys 2400 and Arkray Aution Wongkrajang P. Optimal criteria for microscopic review of urinalysis
Max for testing urine chemistry and detection of bacteriuria. Clin Chim following use of automated urine analyzer. Clin Chim Acta. 2015;
Acta. 2007;377:98–102. 439:1–4.

www.labmedicine.com Lab Medicine 2016;47:2;124–133 133

DOI: 10.1093/labmed/lmw002