0104460715190c501V13.

UREAL
Urea/BUN
Order information
Analyzer(s) on which cobas c pack(s) can be used
04460715 190 Urea/BUN 500 tests System‑ID 07 6303 9 cobas c 311, cobas c 501/502
10759350 190 Calibrator f.a.s. (12 x 3 mL) Code 401
12149435 122 Precinorm U plus (10 x 3 mL) Code 300
12149443 122 Precipath U plus (10 x 3 mL) Code 301
05117003 190 PreciControl ClinChem Multi 1 (20 x 5 mL) Code 391
05947626 190 PreciControl ClinChem Multi 1 (4 x 5 mL) Code 391
05117216 190 PreciControl ClinChem Multi 2 (20 x 5 mL) Code 392
05947774 190 PreciControl ClinChem Multi 2 (4 x 5 mL) Code 392
04489357 190 Diluent NaCl 9 % (50 mL) System‑ID 07 6869 3

English Urease

System information Urea + 2 H2O 2 NH4+ + CO32-

For cobas c 311 analyzer: In the second reaction 2‑oxoglutarate reacts with ammonium in the
UREAL: ACN 418 (serum/plasma) presence of glutamate dehydrogenase (GLDH) and the coenzyme NADH to
U‑BUN: ACN 421 (serum/plasma) produce L‑glutamate. In this reaction two moles of NADH are oxidized to
NAD+ for each mole of urea hydrolyzed.
URELU: ACN 417 (urine)
UBUNU: ACN 428 (urine) GLDH
SUREA: ACN 419 (STAT, reaction time: 4, serum/plasma) NH4+ + 2‑oxoglutarate + NADH L‑glutamate + NAD+ + H2O
SUBUN: ACN 427 (STAT, reaction time: 4, serum/plasma) The rate of decrease in the NADH concentration is directly proportional to
SUREU: ACN 420 (STAT, reaction time: 4, urine) the urea concentration in the specimen and is measured photometrically.
SBUNU: ACN 429 (STAT, reaction time: 4, urine) Reagents - working solutions
For cobas c 501 analyzer:
R1 NaCl 9 %
UREAL: ACN 418 (serum/plasma/urine)
U‑BUN: ACN 421 (serum/plasma/urine) R2 TRIS buffer: 220 mmol/L, pH 8.6; 2‑oxoglutarate: 73 mmol/L;
NADH: 2.5 mmol/L; ADP: 6.5 mmol/L; urease (jack bean):
SUREA: ACN 419 (STAT, reaction time: 4, serum/plasma/urine)
≥ 300 µkat/L; GLDH (bovine liver): ≥ 80 µkat/L; preservative;
SUBUN: ACN 427 (STAT, reaction time: 4, serum/plasma/urine)
nonreactive stabilizers
For cobas c 502 analyzer:
R1 is in position C and R2 is in position B.
UREAL: ACN 8418 (serum/plasma)
U‑BUN: ACN 8421 (serum/plasma) Precautions and warnings
URELU: ACN 8417 (urine) For in vitro diagnostic use.
Exercise the normal precautions required for handling all laboratory
UBUNU: ACN 8428 (urine) reagents.
SUREA: ACN 8419 (STAT, reaction time: 4, serum/plasma) Disposal of all waste material should be in accordance with local guidelines.
SUBUN: ACN 8427 (STAT, reaction time: 4, serum/plasma) Safety data sheet available for professional user on request.
SUREU: ACN 8420 (STAT, reaction time: 4, urine) Reagent handling
SBUNU: ACN 8429 (STAT, reaction time: 4, urine) Ready for use
Intended use Storage and stability
In vitro test for the quantitative determination of urea/urea nitrogen in UREAL
human serum, plasma and urine on Roche/Hitachi cobas c systems.
Shelf life at 2‑8 °C: See expiration date
Summary1
on cobas c pack
Urea is the major end product of protein nitrogen metabolism. It is
synthesized by the urea cycle in the liver from ammonia which is produced label.
by amino acid deamination. Urea is excreted mostly by the kidneys but On‑board in use and refrigerated on the analyzer: 8 weeks
minimal amounts are also excreted in sweat and degraded in the intestines
by bacterial action. Diluent NaCl 9 %
Determination of blood urea nitrogen is the most widely used screening test Shelf life at 2‑8 °C: See expiration date
for renal function. When used in conjunction with serum creatinine on cobas c pack
determinations it can aid in the differential diagnosis of the three types of label.
azotemia: prerenal, renal and postrenal.
Elevations in blood urea nitrogen concentration are seen in inadequate On‑board in use and refrigerated on the analyzer: 12 weeks
renal perfusion, shock, diminished blood volume (prerenal causes), chronic Specimen collection and preparation
nephritis, nephrosclerosis, tubular necrosis, glomerular nephritis (renal
causes) and urinary tract obstruction (postrenal causes). Transient For specimen collection and preparation only use suitable tubes or
elevations may also be seen during periods of high protein intake. collection containers.
Unpredictable levels occur with liver diseases. Only the specimens listed below were tested and found acceptable.
Serum
Test principle Plasma: Li‑heparin and K2‑EDTA plasma. Do not use ammonium heparin.
Kinetic test with urease and glutamate dehydrogenase.2,3,4,5 The sample types listed were tested with a selection of sample collection
Urea is hydrolyzed by urease to form ammonium and carbonate. tubes that were commercially available at the time of testing, i.e. not all
available tubes of all manufacturers were tested. Sample collection systems

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Urea/BUN

from various manufacturers may contain differing materials which could Sample volumes Sample Sample dilution
affect the test results in some cases. When processing samples in primary
tubes (sample collection systems), follow the instructions of the tube Sample Diluent (NaCl)
manufacturer. Normal 2 µL – –
Urine Decreased 6 µL 15 µL 120 µL
Bacterial growth in the specimen and high atmospheric ammonia
concentrations as well as contamination by ammonium ions may cause Increased 2 µL – –
erroneously elevated results.
cobas c 502 test definition
Stability in serum/plasma:6 7 days at 15‑25 °C Assay type Rate A
7 days at 2‑8 °C Reaction time / Assay points 10 / 16‑28 (STAT 4 / 16‑28)
1 year at (-15)‑(-25) °C Wavelength (sub/main) 700/340 nm
Stability in urine:6 2 days at 15‑25 °C Reaction direction Decrease
7 days at 2‑8 °C Units mmol/L (mg/dL, g/L)
1 month at (-15)‑(-25) °C Reagent pipetting Diluent (H2O)
Centrifuge samples containing precipitates before performing the assay. R1 10 µL 90 µL
See the limitations and interferences section for details about possible R2 38 µL 110 µL
sample interferences.
Sample volumes Sample Sample dilution
Materials provided
Sample Diluent (NaCl)
See “Reagents – working solutions” section for reagents.
Normal 2 µL – –
Materials required (but not provided)
Decreased 6 µL 15 µL 120 µL
▪ See “Order information” section
▪ General laboratory equipment Increased 4 µL – –
Assay Application for urine
For optimum performance of the assay follow the directions given in this cobas c 311 test definition
document for the analyzer concerned. Refer to the appropriate operator’s
manual for analyzer‑specific assay instructions. Assay type Rate A
The performance of applications not validated by Roche is not warranted Reaction time / Assay points 10 / 10‑19 (STAT 4 / 10‑19)
and must be defined by the user.
Wavelength (sub/main) 700/340 nm
Application for serum and plasma
Reaction direction Decrease
cobas c 311 test definition Units mmol/L (mg/dL, g/L)
Assay type Rate A Reagent pipetting Diluent (H2O)
Reaction time / Assay points 10 / 10‑19 (STAT 4 / 10‑19) R1 10 µL 90 µL
Wavelength (sub/main) 700/340 nm R2 38 µL 110 µL
Reaction direction Decrease Sample volumes Sample Sample dilution
Units mmol/L (mg/dL, g/L) Sample Diluent (NaCl)
Reagent pipetting Diluent (H2O) Normal 2 µL 3 µL 147 µL
R1 10 µL 90 µL Decreased 2 µL 2 µL 178 µL
R2 38 µL 110 µL Increased 2 µL – –
Sample volumes Sample Sample dilution
cobas c 501/502 test definition
Sample Diluent (NaCl)
Assay type Rate A
Normal 2 µL – –
Reaction time / Assay points 10 / 16‑28 (STAT 4 / 16‑28)
Decreased 6 µL 15 µL 120 µL
Wavelength (sub/main) 700/340 nm
Increased 2 µL – –
Reaction direction Decrease
cobas c 501 test definition Units mmol/L (mg/dL, g/L)
Assay type Rate A Reagent pipetting Diluent (H2O)
Reaction time / Assay points 10 / 16‑28 (STAT 4 / 16‑28) R1 10 µL 90 µL
Wavelength (sub/main) 700/340 nm R2 38 µL 110 µL
Reaction direction Decrease Sample volumes Sample Sample dilution
Units mmol/L (mg/dL, g/L) Sample Diluent (NaCl)
Reagent pipetting Diluent (H2O) Normal 2 µL 3 µL 147 µL
R1 10 µL 90 µL Decreased 2 µL 2 µL 178 µL
R2 38 µL 110 µL Increased 2 µL – –

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Calibration ACTION REQUIRED

Special Wash Programming: The use of special wash steps is mandatory
Calibrators S1: H2O when certain test combinations are run together on cobas c systems. The
S2: C.f.a.s. latest version of the carry‑over evasion list can be found with the NaOHD-
SMS-SmpCln1+2-SCCS Method Sheets. For further instructions refer to the
Calibration mode Linear operator’s manual. cobas c 502 analyzer: All special wash programming
necessary for avoiding carry‑over is available via the cobas link, manual
Calibration frequency 2‑point calibration input is required in certain cases.
• after 4 weeks on board
Where required, special wash/carry‑over evasion programming must
• after reagent lot change be implemented prior to reporting results with this test.
• as required following quality control
procedures Limits and ranges
Measuring range
Calibration interval may be extended based on acceptable verification of
calibration by the laboratory. Serum/plasma
Traceability: This method has been standardized against ID/MS. 0.5‑40 mmol/L (3.0‑240 mg/dL urea, 1.4‑112 mg/dL urea nitrogen)
Determine samples having higher concentrations via the rerun function.
Quality control Dilution of samples via the rerun function is a 1:3 dilution. Results from
Serum/plasma samples diluted using the rerun function are automatically multiplied by a
For quality control, use control materials as listed in the "Order information" factor of 3.
section. Urine
In addition, other suitable control material can be used. 1‑2000 mmol/L (6‑12000 mg/dL urea, 2.8‑5600 mg/dL urea nitrogen)
Urine Determine samples having higher concentrations via the rerun function.
Quantitative urine controls are recommended for routine quality control. Dilution of samples via the rerun function is a 1:1.8 dilution. Results from
samples diluted using the rerun function are automatically multiplied by a
The control intervals and limits should be adapted to each laboratory’s factor of 1.8.
individual requirements. Values obtained should fall within the defined
limits. Each laboratory should establish corrective measures to be taken if Determine samples having concentrations lower than the technical limit of
values fall outside the defined limits. 40 mmol/L (240 mg/dL urea and 112 mg/dL urea nitrogen) via the rerun
function. Samples are measured undiluted.
Follow the applicable government regulations and local guidelines for
quality control. Lower limits of measurement
Calculation Lower detection limit of the test
cobas c systems automatically calculate the analyte concentration of each Serum/plasma
sample. 0.5 mmol/L (3.0 mg/dL urea, 1.4 mg/dL urea nitrogen)
The lower detection limit represents the lowest measurable analyte level
Conversion factors: mmol/L urea x 6.006 = mg/dL urea that can be distinguished from zero. It is calculated as the value lying 3
mmol/L urea x 0.06006 = g/L urea standard deviations above that of the lowest standard (standard 1 + 3 SD,
repeatability, n = 21).
mmol/L urea nitrogen x 2.801 = mg/dL urea nitrogen
Urine
mmol/L urea nitrogen x 0.02801 = g/L urea nitrogen 1 mmol/L (6 mg/dL urea, 2.8 mg/dL urea nitrogen)
mg/dL urea x 0.467 = mg/dL urea nitrogen The lower detection limit represents the lowest measurable analyte level
When 24‑hour urine is used as the specimen, multiply the result by the that can be distinguished from zero. It is calculated as the value lying 3
24‑hour volume to obtain values in g or mmol/24 hours. standard deviations above that of the lowest standard (standard 1 + 3 SD,
repeatability, n = 21).
Limitations - interference
Expected values
Criterion: Recovery within ± 10 % of initial value at a urea concentration of
8.3 mmol/L (49.8 mg/dL urea, 23.2 mg/dL urea nitrogen) in serum/plasma Urea:
and at a urea concentration of 150 mmol/L (901 mg/dL urea, 421 mg/dL
urea nitrogen) in urine. Recovery within ± 10 % for drug interference. Serum/plasma11
Serum/plasma Adults 2.76‑8.07 mmol/L (16.6‑48.5 mg/dL)
Icterus:7 No significant interference up to an I index of 60 for conjugated Urine
and unconjugated bilirubin (approximate conjugated and unconjugated
bilirubin concentration: 1026 µmol/L (60 mg/dL)). 24‑hour urine12 428‑714 mmol/24 h (25.7‑42.9 g/24 h),
Hemolysis:7 No significant interference up to an H index of 1000 corresponding to
(approximate hemoglobin concentration: 621 µmol/L (1000 mg/dL)). 286‑595 mmol/L (1.71‑3.57 g/dL)a
a) Based on average urine output of 1.2‑1.5 L/24 h
Lipemia (Intralipid):7 No significant interference up to an L index of 1000.
There is poor correlation between the L index (corresponds to turbidity) and
triglycerides concentration. Urea nitrogen (BUN):
Ammonium ions may cause erroneously elevated results. Serum/plasma12
Drugs: No interference was found at therapeutic concentrations using Adults (18‑60 years) 2.14‑7.14 mmol/L 6‑20 mg/dL
common drug panels.8,9
Adults (60‑90 years) 2.86‑8.21 mmol/L 8‑23 mg/dL
In very rare cases, gammopathy, in particular type IgM (Waldenström’s
macroglobulinemia), may cause unreliable results.10 Infants (< 1 year) 1.43‑6.78 mmol/L 4‑19 mg/dL
Urine Infants/children 1.79‑6.43 mmol/L 5‑18 mg/dL
Drugs: No interference was found at therapeutic concentrations using
common drug panels.9
For diagnostic purposes, the results should always be assessed in Urine
conjunction with the patient’s medical history, clinical examination and other
findings.

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24‑hour urine12 428‑714 mmol/24 h (12‑20 g/24 h), Passing/Bablok13 Linear regression

corresponding to y = 0.990x + 0.138 mmol/L y = 0.976x + 0.303 mmol/L
286‑595 mmol/L (801‑1666 mg/dL)b
τ = 0.959 r = 0.998
b) Based on average urine output of 1.2‑1.5 L/24 h
The sample concentrations were between 2.27 and 39.4 mmol/L (13.6 and
Each laboratory should investigate the transferability of the expected values
to its own patient population and if necessary determine its own reference 237 mg/dL urea).
ranges. Urine
Specific performance data Sample size (n) = 267
Representative performance data on the analyzers are given below.
Results obtained in individual laboratories may differ. Passing/Bablok13 Linear regression
Precision y = 1.006x - 6.50 mmol/L y = 1.035x - 14.1 mmol/L
Precision was determined using human samples and controls in an internal τ = 0.949 r = 0.998
protocol with repeatability (n = 21) and intermediate precision
(serum/plasma: 3 aliquots per run, 1 run per day, 21 days; urine: 3 aliquots The sample concentrations were between 39.0 and 1314 mmol/L
per run, 1 run per day, 10 days). The following results were obtained: (234 and 7892 mg/dL urea).
Serum/plasma References
1 Rock RC, Walker WG, Jennings CD. Nitrogen metabolites and renal
Repeatability Mean SD CV function. In: Tietz NW, ed. Fundamentals of Clinical Chemistry. 3rd ed.
mmol/L mmol/L % Philadelphia: WB Saunders 1987;669–704.
(mg/dL urea) (mg/dL urea) 2 Richterich R, Colombo JP. Klinische Chemie. 4th ed. Basel: Karger S
Precinorm U 6.74 (40.5) 0.07 (0.4) 1.0 1978:319-324.
3 Talke H, Schubert GA. Enzymatische Harnstoffbestimmung in Blut und
Precipath U 23.4 (141) 0.2 (1) 0.9 Serum im optischen Test nach Warburg. Klin Wochenschr
Human serum 1 9.18 (55.1) 0.09 (0.5) 1.0 1965;43:174.
Human serum 2 15.1 (90.7) 0.1 (0.6) 0.9 4 Tiffany TO, Jansen JM, Burtis CA, et al. Enzymatic kinetic rate and
end-point analyses of substrate, by use of a GeMSAEC Fast Analyzer.
Intermediate precision Mean SD CV Clin Chem 1972;18:829-840.
mmol/L mmol/L % 5 Sampson EJ, Baired MA, Burtis CA, et al. A coupled-enzyme
equilibrium method for measuring urea in serum: Optimization and
(mg/dL urea) (mg/dL urea) evaluation of the AACC study group on urea candidate reference
Precinorm U 6.66 (40.0) 0.08 (0.5) 1.2 method. Clin Chem 1980;26:816-826.
Precipath U 23.2 (139) 0.3 (2) 1.1 6 WHO Publication: Use of anticoagulants in diagnostic laboratory
investigations, WHO/DIL/LAB/99.1 Rev.2:Jan 2002.
Human serum 3 9.13 (54.8) 0.10 (0.6) 1.1 7 Glick MR, Ryder KW, Jackson SA. Graphical Comparisons of
Human serum 4 14.9 (89.5) 0.2 (1.2) 1.3 Interferences in Clinical Chemistry Instrumentation. Clin Chem
1986;32:470-475.
8 Breuer J. Report on the Symposium “Drug effects in Clinical Chemistry
Urine Methods”. Eur J Clin Chem Clin Biochem 1996;34:385-386.
Repeatability Mean SD CV 9 Sonntag O, Scholer A. Drug interference in clinical chemistry:
recommendation of drugs and their concentrations to be used in drug
mmol/L mmol/L % interference studies. Ann Clin Biochem 2001;38:376-385.
(mg/dL urea) (mg/dL urea)
10 Bakker AJ, Mücke M. Gammopathy interference in clinical chemistry
Control level 1 161 (967) 4 (24) 2.2 assays: mechanisms, detection and prevention.
Clin Chem Lab Med 2007;45(9):1240-1243.
Control level 2 288 (1730) 3 (18) 1.2
11 Löhr B, El-Samalouti V, Junge W, et al. Reference Range Study for
Human urine 1 324 (1946) 4 (24) 1.3 Various Parameters on Roche Clinical Chemistry Analyzers. Clin Lab
Human urine 2 137 (823) 3 (18) 1.9 2009;55:465-471.
12 Wu AHB, ed. Tietz Clinical Guide to Laboratory Tests, 4th edition. St.
Intermediate precision Mean SD CV Louis (MO): Saunders Elsevier 2006;1096.
mmol/L mmol/L % 13 Bablok W, Passing H, Bender R, et al. A general regression procedure
(mg/dL urea) (mg/dL urea) for method transformation. Application of linear regression procedures
for method comparison studies in clinical chemistry, Part III. J Clin
Control level 1 154 (925) 4 (24) 2.7 Chem Clin Biochem 1988 Nov;26(11):783-790.
Control level 2 280 (1682) 6 (36) 2.3 A point (period/stop) is always used in this Method Sheet as the decimal
Human urine 3 316 (1898) 6 (36) 2.0 separator to mark the border between the integral and the fractional parts of
a decimal numeral. Separators for thousands are not used.
Human urine 4 133 (799) 3 (18) 2.4
Symbols
Method comparison Roche Diagnostics uses the following symbols and signs in addition to
Urea values for human serum, plasma and urine samples obtained on a those listed in the ISO 15223‑1 standard (for USA: see dialog.roche.com for
cobas c 501 analyzer (y) were compared with those determined on definition of symbols used):
Roche/Hitachi 917/MODULAR P analyzers (x), using the corresponding
Roche/Hitachi reagent. Contents of kit
Serum/plasma Volume after reconstitution or mixing
Sample size (n) = 175 GTIN Global Trade Item Number

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COBAS, COBAS C, PRECINORM, PRECIPATH and PRECICONTROL are trademarks of Roche.

All other product names and trademarks are the property of their respective owners.
Additions, deletions or changes are indicated by a change bar in the margin.
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