0104460715190c501V12.

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 Roche/Hitachi 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
10171743 122 Precinorm U (20 x 5 mL) Code 300
10171735 122 Precinorm U (4 x 5 mL) Code 300
10171778 122 Precipath U (20 x 5 mL) Code 301
10171760 122 Precipath U (4 x 5 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 elevations may also be seen during periods of high protein intake.
Unpredictable levels occur with liver diseases.
System information
For cobas c 311 analyzer: Test principle
UREAL: ACN 418 (serum/plasma) Kinetic test with urease and glutamate dehydrogenase.2,3,4,5
U‑BUN: ACN 421 (serum/plasma) Urea is hydrolyzed by urease to form ammonium and carbonate.
URELU: ACN 417 (urine) Urease
UBUNU: ACN 428 (urine) Urea + 2 H2O 2 NH4+ + CO32-
SUREA: ACN 419 (STAT, reaction time: 4, serum/plasma)
In the second reaction 2‑oxoglutarate reacts with ammonium in the
SUBUN: ACN 427 (STAT, reaction time: 4, serum/plasma) presence of glutamate dehydrogenase (GLDH) and the coenzyme NADH to
SUREU: ACN 420 (STAT, reaction time: 4, urine) produce L‑glutamate. In this reaction two moles of NADH are oxidized to
SBUNU: ACN 429 (STAT, reaction time: 4, urine) NAD+ for each mole of urea hydrolyzed.
For cobas c 501 analyzer: GLDH
UREAL: ACN 418 (serum/plasma/urine) NH4+ + 2‑oxoglutarate + NADH L‑glutamate + NAD+ + H2O
U‑BUN: ACN 421 (serum/plasma/urine)
The rate of decrease in the NADH concentration is directly proportional to
SUREA: ACN 419 (STAT, reaction time: 4, serum/plasma/urine) the urea concentration in the specimen and is measured photometrically.
SUBUN: ACN 427 (STAT, reaction time: 4, serum/plasma/urine)
Reagents - working solutions
For cobas c 502 analyzer:
UREAL: ACN 8418 (serum/plasma) R1 NaCl 9 %
U‑BUN: ACN 8421 (serum/plasma) R2 TRIS buffer: 220 mmol/L, pH 8.6; 2‑oxoglutarate: 73 mmol/L;
URELU: ACN 8417 (urine) NADH: 2.5 mmol/L; ADP: 6.5 mmol/L; urease (jack bean):
UBUNU: ACN 8428 (urine) ≥ 300 µkat/L; GLDH (bovine liver): ≥ 80 µkat/L; preservative;
SUREA: ACN 8419 (STAT, reaction time: 4, serum/plasma) nonreactive stabilizers
SUBUN: ACN 8427 (STAT, reaction time: 4, serum/plasma) R1 is in position C and R2 is in position B.
SUREU: ACN 8420 (STAT, reaction time: 4, urine) Precautions and warnings
SBUNU: ACN 8429 (STAT, reaction time: 4, urine) For in vitro diagnostic use.
Exercise the normal precautions required for handling all laboratory
Intended use reagents.
In vitro test for the quantitative determination of urea/urea nitrogen in Disposal of all waste material should be in accordance with local guidelines.
human serum, plasma and urine on Roche/Hitachi cobas c systems. Safety data sheet available for professional user on request.
Summary1 Reagent handling
Urea is the major end product of protein nitrogen metabolism. It is Ready for use
synthesized by the urea cycle in the liver from ammonia which is produced
by amino acid deamination. Urea is excreted mostly by the kidneys but Storage and stability
minimal amounts are also excreted in sweat and degraded in the intestines
by bacterial action. UREAL
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.
On‑board in use and refrigerated on the analyzer: 8 weeks
Elevations in blood urea nitrogen concentration are seen in inadequate
renal perfusion, shock, diminished blood volume (prerenal causes), chronic Diluent NaCl 9 %
nephritis, nephrosclerosis, tubular necrosis, glomerular nephritis (renal
causes) and urinary tract obstruction (postrenal causes). Transient

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Urea/BUN

Shelf life at 2‑8 °C: See expiration date Assay type Rate A

on cobas c pack Reaction time / Assay points 10 / 16‑28 (STAT 4 / 16‑28)
label.
Wavelength (sub/main) 700/340 nm
On‑board in use and refrigerated on the analyzer: 12 weeks
Reaction direction Decrease
Specimen collection and preparation Units mmol/L (mg/dL, g/L)
For specimen collection and preparation only use suitable tubes or
collection containers. Reagent pipetting Diluent (H2O)
Only the specimens listed below were tested and found acceptable. R1 10 µL 90 µL
Serum
Plasma: Li‑heparin and K2‑EDTA plasma. Do not use ammonium heparin. R2 38 µL 110 µL
The sample types listed were tested with a selection of sample collection Sample volumes Sample Sample dilution
tubes that were commercially available at the time of testing, i.e. not all Sample Diluent (NaCl)
available tubes of all manufacturers were tested. Sample collection systems
from various manufacturers may contain differing materials which could Normal 2 µL – –
affect the test results in some cases. When processing samples in primary Decreased 6 µL 15 µL 120 µL
tubes (sample collection systems), follow the instructions of the tube
manufacturer. Increased 2 µL – –
Urine
cobas c 502 test definition
Bacterial growth in the specimen and high atmospheric ammonia
concentrations as well as contamination by ammonium ions may cause Assay type Rate A
erroneously elevated results.
Reaction time / Assay points 10 / 16‑28 (STAT 4 / 16‑28)
Stability in serum/plasma:6 7 days at 15‑25 °C Wavelength (sub/main) 700/340 nm
7 days at 2‑8 °C Reaction direction Decrease
1 year at (-15)‑(-25) °C Units mmol/L (mg/dL, g/L)
Stability in urine:6 2 days at 15‑25 °C Reagent pipetting Diluent (H2O)
7 days at 2‑8 °C R1 10 µL 90 µL
1 month at (-15)‑(-25) °C R2 38 µL 110 µL
Centrifuge samples containing precipitates before performing the assay. 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 Increased 4 µL – –
▪ General laboratory equipment Application for urine
Assay
cobas c 311 test definition
For optimum performance of the assay follow the directions given in this
document for the analyzer concerned. Refer to the appropriate operator’s Assay type Rate A
manual for analyzer‑specific assay instructions.
Reaction time / Assay points 10 / 10‑19 (STAT 4 / 10‑19)
The performance of applications not validated by Roche is not warranted
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)

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Urea/BUN

Reagent pipetting Diluent (H2O) In very rare cases, gammopathy, in particular type IgM (Waldenström’s
macroglobulinemia), may cause unreliable results.10
R1 10 µL 90 µL
Urine
R2 38 µL 110 µL
Drugs: No interference was found at therapeutic concentrations using
Sample volumes Sample Sample dilution common drug panels.9
Sample Diluent (NaCl) For diagnostic purposes, the results should always be assessed in
conjunction with the patient’s medical history, clinical examination and other
Normal 2 µL 3 µL 147 µL findings.
Decreased 2 µL 2 µL 178 µL ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory
Increased 2 µL – – when certain test combinations are run together on Roche/Hitachi
Calibration cobas c systems. The latest version of the carry‑over evasion list can be
found with the NaOHD/SMS/Multiclean/SCCS or the
Calibrators S1: H2O NaOHD/SMS/SmpCln1+2/SCCS Method Sheets. For further instructions
refer to the operator’s manual. cobas c 502 analyzer: All special wash
S2: C.f.a.s. programming necessary for avoiding carry‑over is available via the
Calibration mode Linear cobas link, manual input is not required.
Where required, special wash/carry‑over evasion programming must
Calibration frequency 2‑point calibration be implemented prior to reporting results with this test.
• after 4 weeks on board
• after reagent lot change Limits and ranges
• as required following quality control Measuring range
procedures 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
Roche/Hitachi cobas c systems automatically calculate the analyte Serum/plasma
concentration of each 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). Urea:
Serum/plasma Serum/plasma11
Icterus:7 No significant interference up to an I index of 60 for conjugated
and unconjugated bilirubin (approximate conjugated and unconjugated Adults 2.76‑8.07 mmol/L (16.6‑48.5 mg/dL)
bilirubin concentration: 1026 µmol/L (60 mg/dL)). Urine
Hemolysis:7 No significant interference up to an H index of 1000 24‑hour urine12 428‑714 mmol/24 h (25.7‑42.9 g/24 h),
(approximate hemoglobin concentration: 621 µmol/L (1000 mg/dL)).
corresponding to
Lipemia (Intralipid):7 No significant interference up to an L index of 1000. 286‑595 mmol/L (1.71‑3.57 g/dL)a
There is poor correlation between the L index (corresponds to turbidity) and
a) Based on average urine output of 1.2‑1.5 L/24 h
triglycerides concentration.
Ammonium ions may cause erroneously elevated results. Urea nitrogen (BUN):
Drugs: No interference was found at therapeutic concentrations using
common drug panels.8,9 Serum/plasma12
Adults (18‑60 years) 2.14‑7.14 mmol/L 6‑20 mg/dL

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Urea/BUN

Adults (60‑90 years) 2.86‑8.21 mmol/L 8‑23 mg/dL Method comparison

Infants (< 1 year) 1.43‑6.78 mmol/L 4‑19 mg/dL Urea values for human serum, plasma and urine samples obtained on a
Roche/Hitachi cobas c 501 analyzer (y) were compared with those
Infants/children 1.79‑6.43 mmol/L 5‑18 mg/dL determined on Roche/Hitachi 917/MODULAR P analyzers (x), using the
corresponding Roche/Hitachi reagent.
Serum/plasma
Urine
Sample size (n) = 175
24‑hour urine12 428‑714 mmol/24 h (12‑20 g/24 h),
corresponding to Passing/Bablok13 Linear regression
286‑595 mmol/L (801‑1666 mg/dL)b y = 0.990x + 0.138 mmol/L y = 0.976x + 0.303 mmol/L
b) Based on average urine output of 1.2‑1.5 L/24 h
τ = 0.959 r = 0.998
Each laboratory should investigate the transferability of the expected values The sample concentrations were between 2.27 and 39.4 mmol/L (13.6 and
to its own patient population and if necessary determine its own reference
ranges. 237 mg/dL urea).
Specific performance data Urine
Representative performance data on the analyzers are given below. Sample size (n) = 267
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
protocol with repeatability (n = 21) and intermediate precision τ = 0.949 r = 0.998
(serum/plasma: 3 aliquots per run, 1 run per day, 21 days; urine: 3 aliquots
per run, 1 run per day, 10 days). The following results were obtained: The sample concentrations were between 39.0 and 1314 mmol/L
(234 and 7892 mg/dL urea).
Serum/plasma
References
Repeatability Mean SD CV
1 Rock RC, Walker WG, Jennings CD. Nitrogen metabolites and renal
mmol/L mmol/L % function. In: Tietz NW, ed. Fundamentals of Clinical Chemistry. 3rd ed.
(mg/dL urea) (mg/dL urea) Philadelphia: WB Saunders 1987;669–704.
Precinorm U 6.74 (40.5) 0.07 (0.4) 1.0 2 Richterich R, Colombo JP. Klinische Chemie. 4th ed. Basel: Karger S
1978:319-324.
Precipath U 23.4 (141) 0.2 (1) 0.9 3 Talke H, Schubert GA. Enzymatische Harnstoffbestimmung in Blut und
Human serum 1 9.18 (55.1) 0.09 (0.5) 1.0 Serum im optischen Test nach Warburg. Klin Wochenschr
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
Intermediate precision Mean SD CV end-point analyses of substrate, by use of a GeMSAEC Fast Analyzer.
Clin Chem 1972;18:829-840.
mmol/L mmol/L %
5 Sampson EJ, Baired MA, Burtis CA, et al. A coupled-enzyme
(mg/dL urea) (mg/dL urea) equilibrium method for measuring urea in serum: Optimization and
Precinorm U 6.66 (40.0) 0.08 (0.5) 1.2 evaluation of the AACC study group on urea candidate reference
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
Human serum 3 9.13 (54.8) 0.10 (0.6) 1.1 investigations, WHO/DIL/LAB/99.1 Rev.2:Jan 2002
Human serum 4 14.9 (89.5) 0.2 (1.2) 1.3 7 Glick MR, Ryder KW, Jackson SA. Graphical Comparisons of
Interferences in Clinical Chemistry Instrumentation. Clin Chem
1986;32:470-475.
Urine 8 Breuer J. Report on the Symposium “Drug effects in Clinical Chemistry
Repeatability Mean SD CV Methods”. Eur J Clin Chem Clin Biochem 1996;34:385-386.
9 Sonntag O, Scholer A. Drug interference in clinical chemistry:
mmol/L mmol/L % recommendation of drugs and their concentrations to be used in drug
(mg/dL urea) (mg/dL urea) interference studies. Ann Clin Biochem 2001;38:376-385.
Control level 1 161 (967) 4 (24) 2.2 10 Bakker AJ, Mücke M. Gammopathy interference in clinical chemistry
Control level 2 288 (1730) 3 (18) 1.2 assays: mechanisms, detection and prevention.
Clin Chem Lab Med 2007;45(9):1240-1243.
Human urine 1 324 (1946) 4 (24) 1.3 11 Löhr B, El-Samalouti V, Junge W, et al. Reference Range Study for
Human urine 2 137 (823) 3 (18) 1.9 Various Parameters on Roche Clinical Chemistry Analyzers. Clin Lab
2009;55:465-471.
Intermediate precision Mean SD CV 12 Wu AHB, ed. Tietz Clinical Guide to Laboratory Tests, 4th edition. St.
mmol/L mmol/L % Louis (MO): Saunders Elsevier 2006;1096.
(mg/dL urea) (mg/dL urea) 13 Bablok W, Passing H, Bender R, et al. A general regression procedure
for method transformation. Application of linear regression procedures
Control level 1 154 (925) 4 (24) 2.7 for method comparison studies in clinical chemistry, Part III. J Clin
Control level 2 280 (1682) 6 (36) 2.3 Chem Clin Biochem 1988 Nov;26(11):783-790.
Human urine 3 316 (1898) 6 (36) 2.0 A point (period/stop) is always used in this Method Sheet as the decimal
separator to mark the border between the integral and the fractional parts of
Human urine 4 133 (799) 3 (18) 2.4 a decimal numeral. Separators for thousands are not used.

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Urea/BUN

Symbols
Roche Diagnostics uses the following symbols and signs in addition to
those listed in the ISO 15223‑1 standard.
Contents of kit
Volume after reconstitution or mixing
GTIN Global Trade Item Number

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

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