04460715190V5

UREAL
Urea/BUN
Indicates cobas c systems on which reagents can be used
Order information Roche/Hitachi cobas c systems
Urea/BUN cobas c 311 cobas c 501/502
500 tests Cat. No. 04460715 190 System-ID 07 6303 9
Calibrator f.a.s. (12 x 3 mL) Cat. No. 10759350 190 Code 401
Calibrator f.a.s. (12 x 3 mL, for USA) Cat. No. 10759350 360 Code 401
Precinorm U plus (10 x 3 mL) Cat. No. 12149435 122 Code 300
Precinorm U plus (10 x 3 mL, for USA) Cat. No. 12149435 160 Code 300
Precipath U plus (10 x 3 mL) Cat. No. 12149443 122 Code 301
Precipath U plus (10 x 3 mL, for USA) Cat. No. 12149443 160 Code 301
Precinorm U (20 x 5 mL) Cat. No. 10171743 122 Code 300
Precipath U (20 x 5 mL) Cat. No. 10171778 122 Code 301
Diluent NaCl 9 % (50 mL) Cat. No. 04489357 190 System-ID 07 6869 3

English In the second reaction 2-oxoglutarate reacts with ammonium in the

presence of glutamate dehydrogenase (GLDH) and the coenzyme
System information
NADH to produce L-glutamate. In this reaction two moles of NADH are
For cobas c 311 analyzer:
oxidized to NAD+ for each mole of urea hydrolyzed.
UREAL: ACN 418 (serum/plasma)
U-BUN: ACN 421 (serum/plasma) GLDH
URELU: ACN 417 (urine) NH4+ + 2-oxoglutarate + NADH L-glutamate + NAD+ + H2O
UBUNU: ACN 428 (urine)
SUREA: ACN 419 (STAT, reaction time: 4, serum/plasma) The rate of decrease in the NADH concentration is directly proportional to the
SUBUN: ACN 427 (STAT, reaction time: 4, serum/plasma) urea concentration in the specimen and is measured photometrically.
SUREU: ACN 420 (STAT, reaction time: 4, urine)
Reagents - working solutions
SBUNU: ACN 429 (STAT, reaction time: 4, urine)
R1 NaCl 9 %
For cobas c 501 analyzer:
UREAL: ACN 418 (serum/plasma/urine) R2 TRIS buffer: 220 mmol/L, pH 8.6; 2-oxoglutarate: 73 mmol/L;
U-BUN: ACN 421 (serum/plasma/urine) NADH: 2.5 mmol/L; ADP: 6.5 mmol/L; urease (jack bean): 300 kat/L;
SUREA: ACN 419 (STAT, reaction time: 4, serum/plasma/urine) GLDH (bovine liver): 80 kat/L; preservative; nonreactive stabilizers
SUBUN: ACN 427 (STAT, reaction time: 4, serum/plasma/urine) Precautions and warnings
For in vitro diagnostic use.
For cobas c 502 analyzer: Exercise the normal precautions required for handling all laboratory reagents.
UREAL: ACN 8418 (serum/plasma) Safety data sheet available for professional user on request.
U-BUN: ACN 8421 (serum/plasma) Disposal of all waste material should be in accordance with local guidelines.
URELU: ACN 8417 (urine)
UBUNU: ACN 8428 (urine) Reagent handling
SUREA: ACN 8419 (STAT, reaction time: 4, serum/plasma) Ready for use.
SUBUN: ACN 8427 (STAT, reaction time: 4, serum/plasma)
SUREU: ACN 8420 (STAT, reaction time: 4, urine) Storage and stability
SBUNU: ACN 8429 (STAT, reaction time: 4, urine) UREAL
Intended use Shelf life at 2-8 C: See expiration date on
In vitro test for the quantitative determination of urea/urea nitrogen in human cobas c pack label.
serum, plasma and urine on Roche/Hitachi cobas c systems. On-board in use and refrigerated on the analyzer: 8 weeks

Summary1 Diluent NaCl 9 %

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 by amino acid
deamination. Urea is excreted mostly by the kidneys but minimal amounts are
also excreted in sweat and degraded in the intestines by bacterial action.
Determination of blood urea nitrogen is the most widely used screening
test for renal function. When used in conjunction with serum creatinine
determinations it can aid in the differential diagnosis of the three
types of azotemia: prerenal, renal and postrenal.
Elevations in blood urea nitrogen concentration are seen in inadequate
renal perfusion, shock, diminished blood volume (prerenal causes),
chronic nephritis, nephrosclerosis, tubular necrosis, glomerular nephritis
(renal causes) and urinary tract obstruction (postrenal causes). Transient
elevations may also be seen during periods of high protein intake.
Unpredictable levels occur with liver diseases.
Test principle
Kinetic test with urease and glutamate dehydrogenase.2,3,4,5
Urea is hydrolyzed by urease to form ammonium and carbonate.
Urease
Urea + 2 H2O 2 NH4+ + CO32-
2010-06, V 5 English
Shelf life at 2-8 C: See expiration date on
cobas c pack label.
On-board in use and refrigerated on the analyzer: 12 weeks
Specimen collection and preparation
For specimen collection and preparation, only use suitable
tubes or collection containers.
Only the specimens listed below were tested and found acceptable.
Serum
Plasma: Li-heparin and K2-EDTA plasma. Do not use ammonium heparin.
The sample types listed were tested with a selection of sample collection tubes
that were commercially available at the time of testing, i.e. not all available
tubes of all manufacturers were tested. Sample collection systems from
various manufacturers may contain differing materials which could affect
the test results in some cases. When processing samples in primary tubes
(sample collection systems), follow the instructions of the tube manufacturer.
Urine
Bacterial growth in the specimen and high atmospheric ammonia
concentrations as well as contamination by ammonium ions may
cause erroneously elevated results.
1/4 cobas c systems
 400/800

Urea/BUN

Order information
COBAS INTEGRA 500 Tests Cat. No. 04460715 190 Indicates analyzer(s) on which cobas c pack can be
Urea/BUN System-ID 07 6303 9 used
Calibrator f.a.s. 12 3 mL Cat. No. 10759350 190
Calibrator f.a.s. (for USA) 12 3 mL Cat. No. 10759350 360
System-ID 07 3718 6
Precinorm U 20 5 mL Cat. No. 10171743 122
System-ID 07 7997 0
Precipath U 20 5 mL Cat. No. 10171778 122
System-ID 07 7998 9
Precinorm U plus 10 3 mL Cat. No. 12149435 122
Precinorm U plus (for USA) 10 3 mL Cat. No. 12149435 160
System-ID 07 7999 7
Precipath U plus 10 3 mL Cat. No. 12149443 122
Precipath U plus (for USA) 10 3 mL Cat. No. 12149443 160
System-ID 07 8000 6

System information Urea + 2 H2O Urease

2 NH4+ + CO32-
COBAS INTEGRA Urea/BUN (UREAL)
Test UREL, test ID 0-003 for serum and plasma GLDH
Test URELU, test ID 0-004 for urine NH4+ + 2-oxoglutarate + NADH
L-glutamate + NAD+ + H2O
Intended use
In vitro test for the quantitative determination of the urea/BUN The rate of decrease in the NADH concentration is directly
(blood urea nitrogen) concentration in human serum, plasma, proportional to the urea concentration in the specimen. It is
and urine on COBAS INTEGRA systems. determined by measuring the absorbance at 340 nm.
Summary1
Reagents - working solutions
Urea is the major end product of protein nitrogen metabolism.
It is synthesized by the urea cycle in the liver from ammonia Components Concentrations
which is produced by amino acid deamination. Urea is excreted R Test
mostly by the kidneys but minimal amounts are also excreted in TRIS 220 45 mmol/L
sweat and degraded in the intestines by bacterial action. 2-Oxoglutarate 73 15 mmol/L
Determination of blood urea nitrogen is the most widely NADH 2.5 0.5 mmol/L
used screening test for renal function. When used in ADP 6.5 1.4 mmol/L
conjunction with serum creatinine determinations it
Urease (jack bean) 300 61 kat/L ( 3.7 kU/L)
can aid in the differential diagnosis of the three types of
GLDH (bovine) 80 16 kat/L ( 1.0 kU/L)
azotemia: prerenal, renal, and postrenal.
pH 8.6 8.6
Elevations in blood urea nitrogen concentration are seen in
inadequate renal perfusion, shock, diminished blood volume The reagent contains nonreactive stabilizers.
(prerenal causes), chronic nephritis, nephrosclerosis, tubular
necrosis, glomerular-nephritis (renal causes), and urinary Precautions and warnings
tract obstruction (postrenal causes). Transient elevations Pay attention to all precautions and warnings listed in this
may also be seen during periods of high protein intake. Method Manual, Chapter 1, Introduction.
Unpredictable levels occur with liver diseases.
Reagent handling
Test principle
Ready for use.
Kinetic test with urease and glutamate dehydrogenase.2,3,4,5
Urea is hydrolyzed by urease to form ammonium and carbonate. In
Storage and stability
the second reaction 2-oxoglutarate reacts with ammonium in the
presence of glutamate dehydrogenase (GLDH) and the coenzyme Shelf life at 2 to 8 C See expiration date on
NADH to produce L-glutamate. In this reaction two moles of cobas c pack label
NADH are oxidized to NAD for each mole of urea hydrolyzed. COBAS INTEGRA 400/400 plus systems
On-board in use at 10 to 15 C 8 weeks
COBAS INTEGRA 800 systems
On-board in use at 8 C 8 weeks

2008-11, V 3 EN 1/4 UREAL

 Substrates
4 0 0 /8 0 0

Specimen collection and preparation COBAS INTEGRA 800 test definition

For specimen collection and preparation, only use suitable Measuring mode Absorbance
tubes or collection containers. Abs. calculation mode Kinetic
Only the specimens listed below were tested and found acceptable. Reaction direction Decrease
Serum 340/409 nm
Wavelength A/B
Plasma: Li-heparin, EDTA or fluoride plasma. Do not
Calc. first/last 27/36
use ammonium heparin.
Unit mmol/L
Urine: Bacterial growth in the specimen and high atmospheric
ammonia concentration as well as contamination by ammonium Serum, plasma
ions may cause erroneously elevated results. Reaction mode R-S
The sample types listed were tested with a selection of Urine
sample collection tubes that were commercially available Reaction mode D-R-S
at the time of testing, i.e. not all available tubes of all Predilution factor 50
manufacturers were tested. Sample collection systems from
various manufacturers may contain differing materials which Pipetting parameters
could affect the test results in some cases. When processing Serum, plasma, urine Diluent (H2O)
samples in primary tubes (sample collection systems), follow R 50 L 150 L
the instructions of the tube manufacturer. Sample 2 L 43 L
Stability in serum/plasma:6 7 days at 15-25 C Total volume 245 L
7 days at 2-8 C
Calibration
1 year at (-15)-(-25) C
Calibrator Calibrator f.a.s.
Stability in urine:6 2 days at 15-25 C
Use deionized water as zero
7 days at 2-8 C calibrator.
1 month at (-15)-(-25) C Linear regression
Calibration mode
Centrifuge samples containing precipitates before Calibration replicate Duplicate recommended
performing the assay. Calibration interval Each cobas c pack, every 4 weeks,
Materials provided and as required following quality
See Reagents - working solutions section for reagents. control procedures
Traceability: This method has been standardized against
Assay
SRM 909b.
For optimum performance of the assay follow the
directions given in this document for the analyzer Quality control
concerned. Refer to the appropriate operators manual for Quality control serum, Precinorm U or Precinorm U plus
analyzer-specific assay instructions. plasma Precipath U or Precipath U plus
Application for serum, plasma and urine Quality control urine Quantitative urine controls are
recommended for routine quality
COBAS INTEGRA 400/400 plus test definition control.
Control interval 24 hours recommended
Measuring mode Absorbance
Control sequence User defined
Abs. calculation mode Kinetic
Control after calibration Recommended
Reaction direction Decrease
Wavelength A/B 340/409 nm For quality control, use control materials as listed in
Calc. first/last 23/28 the Order information section. Other suitable control
Unit mmol/L material can be used in addition.
Serum, plasma The control intervals and limits should be adapted to
Reaction mode R-S each laboratorys individual requirements. Values obtained
should fall within the defined limits.
Each laboratory should establish corrective measures to
Urine
be taken if values fall outside the limits.
Reaction mode D-R-S
Follow the applicable government regulations and local
Predilution factor 50
guidelines for quality control.
Pipetting parameters
Calculation
Serum, plasma, urine Diluent (H2O) COBAS INTEGRA analyzers automatically calculate
R 50 L 95 L the analyte concentration of each sample. For more
Sample 2 L 98 L details, please refer to Data Analysis in the Online Help
Total volume 245 L (COBAS INTEGRA 400/400 plus/800 analyzers).
Conversion factors:
mmol/L urea 6.006 = mg/dL urea
mg/dL urea 0.167 = mmol/L urea
mg/dL urea 0.467 = mg/dL urea nitrogen
mmol/L urea = mmol/L urea nitrogen
mg/dL urea nitrogen x 0.357 = mmol/L urea
mmol/L urea nitrogen x 2.801 = mg/dL urea nitrogen

UREAL 2/4 2008-11, V 3 EN

Substrates
4 0 0 /8 0 0

Limitations - interference7 Lower detection limit

Criterion: Recovery within 10 % of initial value. 1.0 mmol/L (0.006 g/dL urea, 2.8 mg/dL urea nitrogen)
Serum, plasma The detection limit represents the lowest measurable analyte
Icterus No significant interference. level that can be distinguished from zero. It is calculated as the
value lying three standard deviations above that of a zero sample
Hemolysis No significant interference. Hemolytic
(zero sample + 3 SD, within-run precision, n = 30).
specimens may cause high absorbance
flagging. Choose diluted sample treatment Expected values
for automatic rerun. Urea:8
Lipemia No significant interference. Lipemic Serum, plasma
specimens may cause high absorbance
Adults ( 65 y) < 8.3 mmol/L (< 50 mg/dL)
flagging. Choose diluted sample treatment
Adults (> 65 y) < 11.9 mmol/L (< 71 mg/dL)
for automatic rerun.
Anticoagulants Do not use ammonium heparin as an Urine
anticoagulant. 24 h urine < 580 mmol/24 h (< 35 g/24 h)
Drugs Therapeutic drug interference was tested 1st morning urine 150-500 mmol/L (0.9-3.0 g/dL)
according to the recommendations of
VDGHa. No interference was found. Urea nitrogen (BUN):

Other Ammonium ions may cause erroneously Serum, plasma9

elevated results. Adults (18-60 years) 6-20 mg/dL
In very rare cases gammopathy, in Adults (60-90 years) 8-23 mg/dL
particular type IgM (Waldenstrms Infant (< 1 year) 4-19 mg/dL
macroglobulinemia), may cause unreliable Infant/child 5-18 mg/dL
results.
Urine
a) Verband der Diagnostica und Diagnostica Gerte Hersteller
24 h urine10 800-1666 mg/dL (12-20 g/24 h)b
For diagnostic purposes, the results should always be b) Based on an average urine output of 1.2-1.5 L/24 h
assessed in conjunction with the patients medical history,
clinical examination and other findings. Each laboratory should investigate the transferability of
the expected values to its own patient population and if
ACTION REQUIRED necessary determine its own reference ranges.
Special wash programming: The use of special wash steps is
mandatory when certain test combinations are run together Specific performance data for serum and plasma
on COBAS INTEGRA analyzers. Refer to the Method Manual, Representative performance data on COBAS INTEGRA
Introduction, Extra Wash Cycles for further instructions. analyzers are given below. Results obtained in individual
Where required, special wash/carry-over evasion programming laboratories may differ.
must be implemented prior to reporting results with this test.
Precision
Measuring range Reproducibility was determined using human samples and
Serum, plasma controls in an internal protocol (within-run n = 20, between-run
0.5-40 mmol/L (3.0-240 mg/dL urea, 1.4-112 mg/dL urea nitrogen) n = 20). The following results were obtained:
Determine samples having higher concentrations via the rerun
Level 1 Level 2
function. Dilution of samples via the rerun function is a 1:10
dilution. Results from samples diluted by the rerun function Mean 4.1 mmol/L 31.0 mmol/L
are automatically multiplied by a factor of 10. (24.6 mg/dL) (186 mg/dL)
Lower detection limit CV within-run 2.3 % 0.89 %
0.5 mmol/L (3.0 mg/dL urea, 1.4 mg/dL urea nitrogen) CV between-run 3.9 % 2.8 %
The detection limit represents the lowest measurable analyte Method comparison
level that can be distinguished from zero. It is calculated as the Urea values for human serum and plasma samples obtained on
value lying three standard deviations above that of a zero sample a COBAS INTEGRA 700 analyzer with the COBAS INTEGRA
(zero sample + 3 SD, within-run precision, n = 30). Urea/BUN reagent (y) were compared to those determined
Urine with commercially available reagents for urea on a COBAS
1.0-2000 mmol/L (0.006-12 g/dL urea, 2.8-5600 mg/dL INTEGRA 700 analyzer (x) and an alternative manufacturers
urea nitrogen) clinical chemistry system (x). Samples were measured in
Determine samples having higher concentrations via the rerun duplicate. Sample size (n) represents all replicates.
function. Dilution of samples via the rerun function is a 1:3 COBAS INTEGRA Alternative
dilution. Results from samples diluted by the rerun function 700 analyzer system
are automatically multiplied by a factor of 3.
Sample size (n) 236 236
Determine samples having lower concentrations via the rerun
Corr. coefficient (r) 0.999 0.999
function. For samples with concentrations lower 40 mmol/L, the
(rs) 0.999 0.999
re-run function reduces the sample predilution factor to 2 (final
dilution 1 + 1 at COBAS INTEGRA 400/400 plus analyzers) or to Lin. regression y = 1.00x + 0.1 mmol/L y = 0.98x + 0.2 mmol/L
1 (undiluted at COBAS INTEGRA 800 analyzers). The results are Passing/Bablok11 y = 1.00x + 0.0 mmol/L y = 1.00x + 0.0 mmol/L
automatically multiplied by the reduced predilution factor. Values ranged from 1.1 to 38.1 mmol/L (6.61 to 229 mg/dL).

2008-11, V 3 EN 3/4 UREAL

 Substrates
4 0 0 /8 0 0

Specific performance data for urine References

Representative performance data on COBAS INTEGRA 1. Rock RC, Walker WG, Jennings CD. Nitrogen metabolites
analyzers are given below. Results obtained in individual and renal function. In: Tietz NW, ed. Fundamentals of Clinical
laboratories may differ. Chemistry. 3rd ed. Philadelphia: WB Saunders 1987:669-704.
2. Richterich R, Colombo JP. Klinische Chemie. 4th ed.
Precision
Basel: Karger S 1978:319-324.
Reproducibility was determined using human samples and
3. Talke H, Schubert GA. Enzymatische Harnstoffbestimmung
controls in an internal protocol (within-run n = 20, between-run
in Blut und Serum im optischen Test nach Warburg.
n = 20). The following results were obtained:
Klin Wochenschr 1965;43:174.
Level 1 Level 2 4. Tiffany TO, Jansen JM, Burtis CA, Overton JB, Scott CD.
Mean 421 mmol/L 679 mmol/L Enzymatic kinetic rate and end-point analyses of substrate, by
(2.53 g/dL) (4.08 g/dL) use of a GeMSAEC Fast Analyzer. Clin Chem 1972;18:829-840.
CV within-run 1.3 % 1.2 % 5. Sampson EJ, Baired MA, Burtis CA, Smith EM, Witte DL,
Bayse DD. A coupled-enzyme equilibrium method for
CV between-run 1.8 % 1.8 %
measuring urea in serum: Optimization and evaluation
Method comparison of the AACC study group on urea candidate reference
Urea values for human urine samples obtained on a COBAS method. Clin Chem 1980;26:816-826.
INTEGRA 700 analyzer with the COBAS INTEGRA Urea/BUN 6. Guder WG, Narayanan S, Wisser H, Zawta B. List of Analytes;
reagent (y) were compared to those determined with commercially Pre-analytical Variables. Brochure in: Samples: From the
available reagents for urea on a COBAS INTEGRA 700 analyzer (x). Patient to the Laboratory. Darmstadt: GIT Verlag 1996.
7. Glick MR, Ryder KW, Jackson SA. Graphical Comparisons
COBAS INTEGRA 700 analyzer
of Interferences in Clinical Chemistry Instrumentation.
Sample size (n) 120 Clin Chem 1986;32:470-474.
Corr. coefficient (r) 0.999 8. Heil W, Koberstein R, Zawta B. Reference Ranges for
(rs) 0.998 Adults and Children. Pre-Analytical Considerations. 8th ed.
Lin. regression y = 1.0x + 1.3 mmol/L 2004 (Published by Roche Diagnostics).
Passing/Bablok11 y = 1.0x + 3.5 mmol/L 9. Tietz NW. Clinical Guide to Laboratory Tests, 3rd ed.
Values ranged from 56.6 to 796 mmol/L (0.340 to 4.78 g/dL). Philadelphia, PA: WB Saunders Co 1995:622-626.
10. Tietz NW. Fundamentals of Clinical Chemistry. Philadelphia,
PA: WB Saunders Co 1976:991.
11. Passing H, Bablok W, et al. A General Regression
Procedure for Method Transformation. J Clin Chem
Clin Biochem 1988;26:783-790.
FOR US CUSTOMERS ONLY: LIMITED WARRANTY
Roche Diagnostics warrants that this product will meet the
specifications stated in the labeling when used in accordance
with such labeling and will be free from defects in material and
workmanship until the expiration date printed on the label.
THIS LIMITED WARRANTY IS IN LIEU OF ANY OTHER
WARRANTY, EXPRESS OR IMPLIED, INCLUDING ANY
IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS
FOR PARTICULAR PURPOSE. IN NO EVENT SHALL ROCHE
DIAGNOSTICS BE LIABLE FOR INCIDENTAL, INDIRECT,
SPECIAL OR CONSEQUENTIAL DAMAGES.

COBAS INTEGRA, COBAS C, PRECINORM and PRECIPATH are trademarks of

Roche.
Other brand or product names are trademarks of their respective holders.
Significant additions or changes are indicated by a change bar in the margin.
2008, Roche Diagnostics

Roche Diagnostics GmbH, D-68298 Mannheim

Distribution in USA by:
Roche Diagnostics, Indianapolis, IN
US Customer Technical Support 1-800-428-2336

UREAL 4/4 2008-11, V 3 EN

UREAL
Urea/BUN
Stability in serum/plasma:6 7 days at 15-25 C Application for urine
7 days at 2-8 C
cobas c 311 test definition
1 year at (-15)-(-25) C
Assay type Rate A
Stability in urine:6 2 days at 15-25 C Reaction time / Assay points 10 / 10-19 (STAT 4 / 10-19)
7 days at 2-8 C Wavelength (sub/main) 700/340 nm
1 month at (-15)-(-25) C Reaction direction Decrease
Centrifuge samples containing precipitates before performing the assay.
Units mmol/L (mg/dL, g/L)
Materials provided Reagent pipetting Diluent (H2O)
See Reagents - working solutions section for reagents. R1 10 L 90 L
Materials required (but not provided) R2 38 L 110 L
See Order information section. Sample volumes Sample Sample dilution
General laboratory equipment Sample Diluent (NaCl)
Assay Normal 2 L 3 L 147 L
For optimum performance of the assay follow the directions given in Decreased 2 L 2 L 178 L
this document for the analyzer concerned. Refer to the appropriate Increased 2 L
operators manual for analyzer-specific assay instructions.
The performance of applications not validated by Roche is not cobas c 501/502 test definition
warranted and must be defined by the user. Assay type Rate A
Application for serum and plasma Reaction time / Assay points 10 / 16-28 (STAT 4 / 16-28)
Wavelength (sub/main) 700/340 nm
cobas c 311 test definition
Reaction direction Decrease
Assay type Rate A
Units mmol/L (mg/dL, g/L)
Reaction time / Assay points 10 / 10-19 (STAT 4 / 10-19)
Wavelength (sub/main) 700/340 nm Reagent pipetting Diluent (H2O)
Reaction direction Decrease R1 10 L 90 L
Units mmol/L (mg/dL, g/L) R2 38 L 110 L
Reagent pipetting Diluent (H2O) Sample volumes Sample Sample dilution
R1 10 L 90 L Sample Diluent (NaCl)
R2 38 L 110 L Normal 2 L 3 L 147 L
Decreased 2 L 2 L 178 L
Sample volumes Sample Sample dilution
Increased 2 L
Sample Diluent (NaCl)
Normal 2 L Calibration
Decreased 6 L 15 L 120 L Calibrators S1: H2O
Increased 4 L S2: C.f.a.s.
Calibration mode Linear
cobas c 501/502 test definition Calibration frequency 2-point calibration
Assay type Rate A - after 4 weeks on board
Reaction time / Assay points 10 / 16-28 (STAT 4 / 16-28) - after reagent lot change
Wavelength (sub/main) 700/340 nm - and as required following quality control
Reaction direction Decrease procedures
Units mmol/L (mg/dL, g/L)
Traceability: This method has been standardized against SRM 909b.
Reagent pipetting Diluent (H2O)
R1 10 L 90 L Quality control
Serum/plasma
R2 38 L 110 L
For quality control, use control materials as listed in the
Sample volumes Sample Sample dilution Order information section.
Sample Diluent (NaCl) Other suitable control material can be used in addition.
Normal 2 L Urine
Decreased 6 L 15 L 120 L Quantitative urine controls are recommended for routine quality control.
Increased 4 L The control intervals and limits should be adapted to each laboratorys
individual requirements. Values obtained should fall within the defined
limits. Each laboratory should establish corrective measures to be
taken if values fall outside the limits.
Follow the applicable government regulations and local guidelines
for quality control.

cobas c systems 2/4 2010-06, V 5 English

04460715190V5

UREAL
Urea/BUN
Calculation Lower limits of measurement
Roche/Hitachi cobas c systems automatically calculate the analyte Lower detection limit of the test
concentration of each sample. Serum/plasma
Conversion factors: mmol/L urea x 6.006 = mg/dL urea 0.5 mmol/L (3.0 mg/dL urea, 1.4 mg/dL urea nitrogen)
mmol/L urea x 0.06006 = g/L urea The lower detection limit represents the lowest measurable analyte
mmol/L urea nitrogen x 2.801 = mg/dL urea nitrogen level that can be distinguished from zero. It is calculated as the value
mmol/L urea nitrogen x 0.02801 = g/L urea nitrogen lying three standard deviations above that of the lowest standard
mg/dL urea x 0.467 = mg/dL urea nitrogen (standard 1 + 3 SD, repeatability, n = 21).
Urine
When 24-hour urine is used as the specimen, multiply the result by the 1 mmol/L (6 mg/dL urea, 2.8 mg/dL urea nitrogen)
24-hour volume to obtain values in g or mmol/24 hours. The lower detection limit represents the lowest measurable analyte
level that can be distinguished from zero. It is calculated as the value
Limitations - interference7
lying three standard deviations above that of the lowest standard
Criterion: Recovery within 10 % of initial value at a urea concentration (standard 1 + 3 SD, repeatability, n = 21).
of 8.3 mmol/L (49.8 mg/dL urea, 23.2 mg/dL urea nitrogen).
Expected values
Serum/plasma
Icterus: No significant interference up to an I index of 60 (approximate Urea:10
conjugated and unconjugated bilirubin concentration: 1026 mol/L (60 mg/dL)). Serum/plasma
Hemolysis: No significant interference up to an H index of 1000 (approximate Adults ( 65 y) < 8.3 mmol/L (< 50 mg/dL)
hemoglobin concentration: 621 mol/L (1000 mg/dL)). Adults (> 65 y) < 11.9 mmol/L (< 71 mg/dL)
Lipemia (Intralipid): No significant interference up to an L index of Urine
1000. There is poor correlation between the L index (corresponds 24-hour urine < 580 mmol/24 h (< 35 g/24 h)
to turbidity) and triglycerides concentration.
1st morning urine 150-500 mmol/L (0.9-3.0 g/dL)
Ammonium ions may cause erroneously elevated results.
Drugs: No interference was found at therapeutic concentrations Urea nitrogen (BUN):
using common drug panels.8,9 Serum/plasma11
In very rare cases, gammopathy, in particular type IgM (Waldenstrms Adults (1860 years) 6-20 mg/dL
macroglobulinemia), may cause unreliable results. Adults (6090 years) 8-23 mg/dL
Urine Infants (< 1 year) 4-19 mg/dL
Drugs: No interference was found at therapeutic concentrations Infants/children 5-18 mg/dL
using common drug panels.9 Urine
For diagnostic purposes, the results should always be assessed in conjunction 24-hour urine12 800-1666 mg/dL (12-20 g/24 h)a
with the patients medical history, clinical examination and other findings. a) Based on an average urine output of 1.2-1.5 L/24 h
ACTION REQUIRED Each laboratory should investigate the transferability of the expected values to
Special Wash Programming: The use of special wash steps is mandatory its own patient population and if necessary determine its own reference ranges.
when certain test combinations are run together on Roche/Hitachi cobas c
systems. The latest version of the Carry over evasion list can be found with Specific performance data
the NaOHD/SMS/Multiclean/SCCS or the NaOHD/SMS/SmpCln1 + 2/SCCS Representative performance data on the analyzers are given below.
Method Sheets. For further instructions refer to the operator manual. Results obtained in individual laboratories may differ.
cobas c 502 analyzer: All special wash programming necessary for avoiding
Precision
carry over is available via the cobas link, manual input is not required.
Precision was determined using human samples and controls in an internal
Where required, special wash/carry over evasion programming must
protocol. Repeatability* (n = 21), intermediate precision** (serum/plasma:
be implemented prior to reporting results with this test.
3 aliquots per run, 1 run per day, 21 days; urine: 3 aliquots per run, 1 run
Limits and ranges per day, 10 days). The following results were obtained:
Measuring range Serum/plasma
Serum/plasma Repeatability* Mean SD CV
0.5-40 mmol/L (3.0-240 mg/dL urea, 1.4-112 mg/dL urea nitrogen) mmol/L (mg/dL urea) mmol/L (mg/dL urea) %
Determine samples having higher concentrations via the rerun function. Precinorm U 6.74 (40.5) 0.07 (0.4) 1.0
Dilution of samples via the rerun function is a 1:3 dilution. Results from samples Precipath U 23.4 (141) 0.2 (1) 0.9
diluted by the rerun function are automatically multiplied by a factor of 3.
Human serum 1 9.18 (55.1) 0.09 (0.5) 1.0
Urine Human serum 2 15.1 (90.7) 0.1 (0.6) 0.9
1-2000 mmol/L (6-12000 mg/dL urea, 2.8-5600 mg/dL urea nitrogen)
Determine samples having higher concentrations via the rerun function. Dilution Intermediate Mean SD CV
of samples via the rerun function is a 1:1.8 dilution. Results from samples precision** mmol/L (mg/dL urea) mmol/L (mg/dL urea) %
diluted by the rerun function are automatically multiplied by a factor of 1.8. Precinorm U 6.66 (40.0) 0.08 (0.5) 1.2
Determine samples having concentrations lower than the technical limit Precipath U 23.2 (139) 0.3 (2) 1.1
of 40 mmol/L (240 mg/dL urea and 112 mg/dL urea nitrogen) via the Human serum 3 9.13 (54.8) 0.10 (0.6) 1.1
rerun function. Samples are measured undiluted. Human serum 4 14.9 (89.5) 0.2 (1.2) 1.3

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UREAL
Urea/BUN
Urine References
Repeatability* Mean SD CV 1. Rock RC, Walker WG, Jennings CD. Nitrogen metabolites and renal
mmol/L (mg/dL urea) mmol/L (mg/dL urea) % function. In: Tietz NW, ed. Fundamentals of Clinical Chemistry. 3rd
ed. Philadelphia: WB Saunders 1987:669704.
Control level 1 161 (967) 4 (24) 2.2
2. Richterich R, Colombo JP. Klinische Chemie. 4th ed. Basel:
Control level 2 288 (1730) 3 (18) 1.2 Karger S 1978:319-324.
Human urine 1 324 (1946) 4 (24) 1.3 3. Talke H, Schubert GA. Enzymatische Harnstoffbestimmung in Blut und
Human urine 2 137 (823) 3 (18) 1.9 Serum im optischen Test nach Warburg. Klin Wochenschr 1965;43:174.
4. Tiffany TO, Jansen JM, Burtis CA, Overton JB, Scott CD. Enzymatic
Intermediate Mean SD CV
kinetic rate and end-point analyses of substrate, by use of a GeMSAEC
precision** mmol/L (mg/dL urea) mmol/L (mg/dL urea) %
Fast Analyzer. Clin Chem 1972;18:829-840.
Control level 1 154 (925) 4 (24) 2.7 5. Sampson EJ, Baired MA, Burtis CA, Smith EM, Witte DL, Bayse DD.
Control level 2 280 (1682) 6 (36) 2.3 A coupled-enzyme equilibrium method for measuring urea in serum:
Human urine 3 316 (1898) 6 (36) 2.0 Optimization and evaluation of the AACC study group on urea candidate
Human urine 4 133 (799) 3 (18) 2.4 reference method. Clin Chem 1980;26:816-826.
* repeatability = within-run precision
6. Use of Anticoagulants in Diagnostic Laboratory Investigations. WHO
Publication WHO/DIL/LAB/99.1 Rev.2. Jan. 2002.
** intermediate precision = total precision / between run precision / between day precision
7. Glick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences
Method comparison in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
Urea values for human serum, plasma and urine samples obtained 8. Breuer J. Report on the Symposium Drug effects in Clinical Chemistry
on a Roche/Hitachi cobas c 501 analyzer (y) were compared with Methods. Eur J Clin Chem Clin Biochem 1996;34:385-386.
those determined on Roche/Hitachi 917/MODULAR P analyzers (x), 9. Sonntag O, Scholer A. Drug interference in clinical chemistry:
using the corresponding Roche/Hitachi reagent. recommendation of drugs and their concentrations to be used in drug
Serum/plasma interference studies. Ann Clin Biochem 2001;38:376-385.
Sample size (n) = 175 10. Heil W, Koberstein R, Zawta B. Reference Ranges for Adults
Passing/Bablok13 Linear regression and Children. Pre-Analytical Considerations. 8th ed. 2004
y = 0.990x + 0.138 mmol/L y = 0.976x + 0.303 mmol/L (Published by Roche Diagnostics).
11. Tietz NW. Clinical Guide to Laboratory Tests, 3rd ed. Philadelphia,
= 0.959 r = 0.998
PA: WB Saunders Co 1995:622-626.
The sample concentrations were between 2.27 and 39.4 mmol/L 12. Tietz NW. Fundamentals of Clinical Chemistry. Philadelphia,
(13.6 and 237 mg/dL urea). PA: WB Saunders Co 1976:991.
Urine 13. Passing H, Bablok W et al. A General Regression Procedure for Method
Sample size (n) = 267 Transformation. J Clin Chem Clin Biochem 1988;26:783-790.
Passing/Bablok13 Linear regression FOR US CUSTOMERS ONLY: LIMITED WARRANTY
y = 1.006x - 6.50 mmol/L y = 1.035x - 14.1 mmol/L Roche Diagnostics warrants that this product will meet the specifications
= 0.949 r = 0.998 stated in the labeling when used in accordance with such labeling and
The sample concentrations were between 39.0 and 1314 mmol/L will be free from defects in material and workmanship until the expiration
(234 and 7892 mg/dL urea). date printed on the label. THIS LIMITED WARRANTY IS IN LIEU OF ANY
OTHER WARRANTY, EXPRESS OR IMPLIED, INCLUDING ANY IMPLIED
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