For VITROS XT 7600 Integrated Systems, use VITROS Chemistry Products FS Diluent Pack 2 for the dilution. Manual Sample Dilution. 1. Dilute the sample with ...
INSTRUCTIONS FOR USE UREA-CREA VITROS XT Chemistry Products UREA-CREA Slides Urea/Creatinine 684 4294 UREA Intended Use ............................................................................................................................................ 2 Summary and Explanation of the Test ..................................................................................................... 2 Principles of the Procedure ...................................................................................................................... 2 Warnings and Precautions ....................................................................................................................... 2 Reagents .................................................................................................................................................. 3 Specimen Collection, Preparation and Storage ........................................................................................ 3 Specimen Pretreatment ............................................................................................................................ 5 Testing Procedure .................................................................................................................................... 5 Calibration ................................................................................................................................................ 5 Quality Control .......................................................................................................................................... 6 Results ...................................................................................................................................................... 7 Limitations of the Procedure ..................................................................................................................... 7 Expected Values ....................................................................................................................................... 8 Performance Characteristics .................................................................................................................... 8 CREA Intended Use .......................................................................................................................................... 14 Summary and Explanation of the Test ................................................................................................... 14 Principles of the Procedure .................................................................................................................... 14 Warnings and Precautions ..................................................................................................................... 15 Reagents ................................................................................................................................................ 15 Specimen Collection, Preparation and Storage ...................................................................................... 16 Specimen Pretreatment .......................................................................................................................... 17 Testing Procedure .................................................................................................................................. 17 Calibration .............................................................................................................................................. 18 Quality Control ........................................................................................................................................ 18 Results .................................................................................................................................................... 19 Limitations of the Procedure ................................................................................................................... 19 Expected Values ..................................................................................................................................... 20 Performance Characteristics .................................................................................................................. 20 References ................................................................................................................................................... 26 Glossary of Symbols ................................................................................................................................. 27 Revision History .......................................................................................................................................... 28 Version 2.0 Pub. No. J65403_EN 1 of 29 INSTRUCTIONS FOR USE UREA Test UREA Urea Rx ONLY Intended Use For in vitro diagnostic use only. The UREA test within the VITROS XT Chemistry Products UREA-CREA Slides quantitatively measures urea concentration, reported either as urea nitrogen or as urea (UREA), in serum, plasma, and urine using VITROS XT 7600 Integrated Systems. Measurements obtained by this device are used in the diagnosis and treatment of certain renal and metabolic diseases. Summary and Explanation of the Test The major pathway of nitrogen excretion is in the form of urea that is synthesized in the liver, released into the blood, and cleared by the kidneys. A high serum urea nitrogen occurs in glomerulonephritis, shock, urinary tract obstruction, pyelonephritis, and other causes of acute and chronic renal failure. Severe congestive heart failure, hyperalimentation, diabetic ketoacidosis, dehydration, and bleeding from the gastrointestinal tract elevate urea nitrogen. Low urea nitrogen often occurs in normal pregnancy, with decreased protein intake, in acute liver failure, and with intravenous fluid administration.1 Principles of the Procedure The UREA test is a multilayered, analytical element coated on a polyester support. A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Water and nonproteinaceous components then travel to the underlying reagent layer, where the urease reaction generates ammonia. The semipermeable membrane allows only ammonia to pass through to the color-forming layer, where it reacts with the indicator to form a dye. The reflection density of the dye is measured and is proportional to the concentration of urea in the sample. Test Type and Conditions Test Type VITROS System* Approximate Incubation Time Temperature Colorimetric XT 7600 5 minutes 37 °C (98.6 °F) * Not all products and systems are available in all countries. Reaction Scheme H2NCONH2 + H2O urease 2NH3 + CO2 Wavelength 670 nm Reaction Sample Volume 4.3 L NH3 + ammonia indicator dye Warnings and Precautions For in vitro diagnostic use only. WARNING: Take care when handling materials and samples of human origin. Since no test method can offer complete assurance that infectious agents are absent, consider all clinical specimens, controls, and calibrators potentially infectious. Handle specimens, solid and liquid waste, and test components in accordance with local regulations and CLSI Guideline M292 or other published biohazard safety guidelines. Version 2.0 Pub. No. J65403_EN 2 of 29 INSTRUCTIONS FOR USE Reagents UREA Urea For specific warnings and precautions for calibrators, quality control materials, and other components, refer to the Instructions for Use for the appropriate VITROS product, or to other manufacturer's product literature. Reagents Slide Ingredients Reactive Ingredients per cm2 Urease (jack bean) 1.2 U and N-propyl-4-(2,6-dinitro-4chlorobenzyl)-quinolonium ethane sulfonate (ammonia indicator) 0.26 mg. Other Ingredients Pigment, binders, buffer, surfactants, stabilizers, chelator and crosslinking agent Slide Diagram 1. Upper slide mount 2. Spreading layer (TiO2) 3. Reagent layer · urease · buffer, pH 7.8 4. Semipermeable membrane 5. Indicator layer: ammonia indicator 6. Support Layer 7. Lower slide mount Reagent Handling Caution: Do not use slide cartridges with damaged or incompletely sealed packaging. · Inspect the packaging for signs of damage. · Be careful when opening the outer packaging with a sharp instrument so as to avoid damage to the individual product packaging. Reagent Preparation IMPORTANT: The slide cartridge must reach room temperature, 1828 °C (6482 °F), before it is unwrapped and loaded into the slide supply. 1. Remove the slide cartridges from storage. 2. Warm the wrapped cartridge at room temperature for 30 minutes when taken from the refrigerator or 60 minutes from the freezer. 3. Unwrap and load the cartridge into the slide supply. Note: Load the cartridges within 24 hours after they reach room temperature, 1828 °C (6482 °F). Reagent Storage and Stability VITROS XT UREA-CREA Slides are stable until the expiration date on the carton when they are stored and handled as specified. Do not use beyond the expiration date. Reagent Unopened Opened Refrigerated Frozen On-analyzer On-analyzer Storage Condition 28 °C (3646 °F) -18 °C ( 0 °F) System turned on System turned off Stability 4 weeks Until expiration date 2 weeks 2 hours · Do not store with or near ammonia, ammonia compounds, or amines. · Verify performance with quality control materials: If the system is turned off for more than 2 hours. After reloading cartridges that have been removed from the slide supply and stored for later use. Specimen Collection, Preparation and Storage Specimens Recommended · Serum · Plasma: Heparin (lithium and sodium) · Urine IMPORTANT: Certain collection devices have been reported to affect other analytes and tests.3 Owing to the variety of specimen collection devices available, Ortho Clinical Version 2.0 Pub. No. J65403_EN 3 of 29 UREA Urea INSTRUCTIONS FOR USE Specimen Collection, Preparation and Storage Diagnostics is unable to provide a definitive statement on the performance of its products with these devices. Confirm that your collection devices are compatible with this test. Specimens Not Recommended · Plasma4 : Sodium fluoride (Fluoride inhibits the enzyme urease.) · Urine: Glacial acetic acid as a preservative Concentrated hydrochloric acid as a preservative Boric acid (in any form) as a preservative Serum and Plasma Specimen Collection and Preparation Collect specimens using standard laboratory procedures.5,6 Note: For details on minimum fill volume requirements, refer to the operating instructions for your system. Patient Preparation No special patient preparation is necessary. Special Precautions Centrifuge serum and plasma specimens and remove the serum or plasma from the cellular material within 4 hours of collection.4 Specimen Handling and Storage · Handle and store specimens in stoppered containers to avoid contamination and evaporation. · Mix samples by gentle inversion and bring to room temperature, 1828 °C (6482 °F), prior to analysis. Specimen Storage and Stability: Serum and Plasma Storage Room temperature Refrigerated Frozen Temperature 1828 °C (6482 °F) 28 °C (3646 °F) -18 °C ( 0 °F) Stability 1 day 5 days 30 days Urine Specimen Collection and Preparation · Collect specimens using standard laboratory procedures.7 · Keep urine specimens refrigerated until analysis. Note: For details on minimum fill volume requirements, refer to the operating instructions for your system. Patient Preparation No special patient preparation is necessary. Special Precautions Urine specimens must be pretreated prior to processing. Refer to "Specimen Pretreatment" for instructions. Specimen Handling and Storage · Handle and store specimens in stoppered containers to avoid contamination and evaporation. · Mix samples by gentle inversion and bring to room temperature, 1828 °C (6482 °F), prior to analysis. Specimen Storage and Stability: Urine Storage Room temperature Refrigerated Frozen Temperature 1828 °C (6482 °F) 28 °C (3646 °F) -18 °C ( 0 °F) Stability 5 days 7 days 6 months 4 of 29 Pub. No. J65403_EN Version 2.0 INSTRUCTIONS FOR USE Specimen Pretreatment UREA Urea Specimen Pretreatment Urine Predilution Pretreatment is managed by the analyzer, no operator intervention is required. Testing Procedure Materials Provided VITROS XT Chemistry Products UREA-CREA Slides Materials Required but Not Provided · VITROS Chemistry Products Calibrator Kit 1 · Quality control materials, such as VITROS Chemistry Products Performance Verifier I and II for serum and plasma · VITROS Chemistry Products 7% BSA · Isotonic saline or reagent-grade water · VITROS Chemistry Products FS Diluent Pack 2 (BSA/Saline) (for on-analyzer dilution of serum and plasma samples) · VITROS Chemistry Products FS Diluent Pack 3 (Specialty Diluent/Water) (for on-analyzer dilution of urine samples) Operating Instructions · Check reagent inventories at least daily to ensure that quantities are sufficient for the planned workload. · For additional information, refer to the operating instructions for your system. IMPORTANT: Bring all fluids and samples to room temperature, 1828 °C (6482 °F), prior to analysis. Sample Dilution Serum and Plasma If urea nitrogen concentrations exceed the system's measuring (reportable or dynamic) range: On-Analyzer Sample Dilution Refer to the operating instructions for your system for more information on the On-Analyzer Dilution Procedure. For VITROS XT 7600 Integrated Systems, use VITROS Chemistry Products FS Diluent Pack 2 for the dilution. Manual Sample Dilution 1. Dilute the sample with 1 part sample and 1 part VITROS 7% BSA. 2. Reanalyze. 3. Multiply the results by 2 to obtain an estimate of the original sample's urea nitrogen concentration. Urine If urea nitrogen concentrations exceed the system's measuring (reportable or dynamic) range: On-Analyzer Sample Dilution Refer to the operating instructions for your system for more information on the On-Analyzer Dilution Procedure. For VITROS XT 7600 Integrated Systems, use VITROS Chemistry Products FS Diluent Pack 3 for the dilution. Manual Sample Dilution 1. Dilute the sample with 1 part sample and 1 part isotonic saline or reagent-grade water. 2. Reanalyze. 3. Multiply the results by 2 to obtain an estimate of the original sample's urea nitrogen concentration. Calibration Required Calibrators VITROS Chemistry Products Calibrator Kit 1 Note: The same VITROS Calibrator Kit is used to calibrate serum, plasma, and urine. However, specific supplementary assigned values (SAVs) are applied for each body fluid. Version 2.0 Pub. No. J65403_EN 5 of 29 UREA Urea INSTRUCTIONS FOR USE Quality Control Calibrator Preparation, Handling, and Storage Refer to the Instructions for Use for VITROS Calibrator Kit 1. Note: After reconstituting calibrators, do not dilute further when calibrating for urine. Calibration Procedure Refer to the operating instructions for your system. When to Calibrate Calibrate: · When the slide lot number changes. · When critical system parts are replaced due to service or maintenance. · When government regulations require. For example, in the USA, CLIA regulations require calibration or calibration verification at least once every six months. The UREA test within the VITROS XT UREA-CREA Slides may also need to be calibrated: · If quality control results are consistently outside acceptable range. · After certain service procedures have been performed. For additional information, refer to the operating instructions for your system. Calculations Reflectance from the slide is measured at 670 nm after the fixed incubation time. Once a calibration has been performed for each slide lot, urea nitrogen concentration in unknown samples can be determined using the software-resident endpoint colorimetric math model and the response obtained from each unknown test slide. Validity of a Calibration Calibration parameters are automatically assessed by the system against a set of quality parameters detailed in Review Assay Data screen on VITROS XT Integrated Systems. Failure to meet any of the pre-defined quality parameters results in a failed calibration. The calibration report should be used in conjunction with quality control results to determine the validity of a calibration. Measuring (Reportable or Dynamic) Range Fluid Conventional Units (mg/dL urea N) Serum/Plasma 2.0120.0 Urine* * After multiplying by a 21x dilution factor. 672520 For out-of-range samples, refer to "Sample Dilution." SI Units (mmol/L urea) 0.7142.83 23.91899.39 Alternate Units (mg/dL urea) 4.29257.40 143.725405.40 Traceability of Calibration The Values assigned to the VITROS Chemistry Products Calibrator Kit 1 for UREA are traceable to a CDC Urease/GLDH comparative method8 and National Institute of Standards and Technology (NIST) SRM® 912 urea standard reference material. Quality Control Quality Control Material Selection IMPORTANT: VITROS Performance Verifiers are recommended for use with VITROS XT Integrated Systems. Evaluate the performance of other commercial control fluids for compatibility with this test before using for quality control. · Control materials other than VITROS Performance Verifiers may show a difference when compared with other urea nitrogen methods if they: Depart from a true human matrix. Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives. · Do not use control materials stabilized with ethylene glycol. Serum · Some controls that are low in pH may show a negative bias that may be avoided by reconstituting lyophilates with a bicarbonate diluent instead of with water. 9 6 of 29 Pub. No. J65403_EN Version 2.0 INSTRUCTIONS FOR USE Results UREA Urea · Proficiency survey samples may show a negative bias similar to controls low in pH. Contact the testing agency for instructions because reconstituting with special diluents may affect other analyte values (e.g., reconstituting with sodium bicarbonate will affect sodium proficiency scores).10 · Ammonium bicarbonate diluent should not be used as it will cause a positive bias in test results. Urine For urine specimens, use commercially available urine control materials. IMPORTANT: If using a VITROS XT Integrated Systems in On-Analyzer Dilution Mode, do not manually dilute samples for analysis and do not multiply by a dilution factor after analysis. Refer to the operating instructions for your system for more information on the On-Analyzer Dilution Procedure. Quality Control Procedure Recommendations · Choose control levels that check the clinically relevant range. · Analyze quality control materials in the same manner as patient samples, before or during patient sample processing. · To verify system performance, analyze control materials: After calibration. According to local regulations or at least once each day that the test is being performed. After specified service procedures are performed. Refer to the operating instructions for your system. · If control results fall outside your acceptable range, investigate the cause before deciding whether to report patient results. · For general quality control recommendations, refer to Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Fourth Edition 11or other published guidelines. · For additional information, refer to the operating instructions for your system. Quality Control Material Preparation, Handling, and Storage Refer to the Instructions for Use for VITROS Chemistry Products Performance Verifier I and II or to other manufacturer's product literature. Results Reporting Units and Unit Conversion The VITROS XT Systems may be programmed to report UREA results in conventional, SI, and alternate units. Conventional Units mg/dL urea N SI Units mmol/L urea (mg/dL urea N x 0.3569) Alternate Units mg/dL urea (mg/dL urea N x 2.145) Limitations of the Procedure Known Interferences Ammonium ions may cause an increase in measured UREA value equivalent to the specimen's nitrogen content.12 Serum and Plasma The VITROS XT Chemistry Products UREA-CREA Slides method was screened for interfering substances following CLSI EP07.13,14 The substances listed in the table, when tested at the concentrations indicated, caused the bias shown. For substances that were tested and did not interfere, refer to "Specificity." Interferent Concentration Urea nitrogen Concentration Bias** Interferent* Conv. Units SI Units Conv. Units SI Units (mg/dL) (mmol/L) Conv. Units (mg/dL) SI Units (mmol/L) Total protein 12 g/dL 120 g/L 37 13 -4.3 -1.5 * It is possible that other interfering substances may be encountered. These results are representative; however, your results may differ somewhat due to test-to-test variation. The degree of interference at concentrations other than those listed might not be predictable. ** The bias is an estimate of the maximum bias observed. Version 2.0 Pub. No. J65403_EN 7 of 29 UREA Urea INSTRUCTIONS FOR USE Expected Values Other Limitations Certain drugs and clinical conditions are known to alter UREA concentrations in vivo. For additional information, refer to one of the published summaries.15,16 Expected Values Reference Interval The serum reference interval is the central 95% of results from an internal study of 3160 apparently healthy adults from a working population (612 females and 2548 males). The urine reference interval is based on an external study.17 Conventional Units (mg/dL urea N) SI Units (mmol/L urea) Alternate Units (mg/dL urea) Serum Male 920 3.27.1 1943 Female 717 2.56.1 1536 Urine 24hour 1220 g/day* 428714 mmol/day** 2643 g/day* * Urea nitrogen concentration (mg/dL) x 24-hour volume (dL) = mg/day. To convert mg/day to g/day, divide by 1000. ** Urea nitrogen concentration (mmol/L) x 24-hour volume (L) = mmol/day. Each laboratory should confirm the validity of these intervals for the population it serves. Performance Characteristics Detection Capability The Limit of Quantitation (LoQ) for the UREA test within the VITROS XT UREA-CREA Slides is 2.0 mg/dL for serum/ plasma and 67 mg/dL for urine. The total number of LoQ determinations was 72. The LoQ was established consistent with CLSI EP17.18 Fluid Type LoQ* Conventional Units (mg/dL Urea N) Serum/Plasma 2.0 Urine 67 * The Total Error goal used to accept the LoQ was 1.2 mg/dL for serum and 21 mg/dL Urea N for urine. SI Units (mmol/L ) 0.71 23.91 Method Comparison The plots and tables below show the results of a method comparison study with serum samples and urine samples analyzed on the VITROS XT 7600 Integrated System and with the Urease/GLDH comparative method.8 The tables also show the results of comparisons with serum and urine samples between the VITROS XT 7600 Integrated System and the VITROS Chemistry Products BUN/UREA Slides on a VITROS 5600 Integrated System. Testing followed CLSI EP09.19 8 of 29 Pub. No. J65403_EN Version 2.0 INSTRUCTIONS FOR USE Performance Characteristics Serum Conventional Units UREA Urea SI Units VITROS XT 7600 System (mg/dL) VITROS XT 7600 System (mmol/L) Comparative Method: Urease/GLDH (mg/dL) Comparative Method: Urease/GLDH (mmol/L) Conventional Units (mg/dL urea N) SI Units (mmol/L urea) Correlation Range of Range of n Slope Coefficient Sample Conc. Intercept Sy.x Sample Conc. Intercept XT 7600 vs. Comparative Method 124 1.05 0.998 3105 -0.43 1.84 1.237.6 -0.15 XT 7600 vs. 5600 124 1.04 0.999 3106 0.00 1.20 0.937.8 0.07 Comparisons made using the same patient samples tested with the VITROS Chemistry Products BUN/UREA Slides run on the VITROS 5600 Integrated System. Sy.x 0.66 0.45 Urine Conventional Units SI Units VITROS XT 7600 System (mg/dL) VITROS XT 7600 System (mmol/L) Version 2.0 Comparative Method: Urease/GLDH (mg/dL) Pub. No. J65403_EN Comparative Method: Urease/GLDH (mmol/L) 9 of 29 UREA Urea INSTRUCTIONS FOR USE Performance Characteristics Conventional Units (mg/dL urea N) SI Units (mmol/L urea) Correlation Range of Range of n Slope Coefficient Sample Conc. Intercept Sy.x Sample Conc. Intercept Sy.x XT 7600 vs. Comparative Method 128 1.05 0.999 1062456 -7.35 27.37 37.8 876.6 -2.62 9.77 XT 7600 vs. 5600 128 1.05 0.999 1052451 -13.21 23.73 38.0 892.1 -4.55 11.05 Comparisons made using the same patient samples tested with the VITROS Chemistry Products BUN/UREA Slides run on the VITROS 5600 Integrated System. Precision Precision was evaluated with patient pools and quality control materials on the VITROS XT 7600 Integrated System following CLSI EP05 .20 The data presented are a representation of test performance and are provided as a guideline. Variables such as sample handling and storage, reagent handling and storage, laboratory environment and system maintenance can affect reproducibility of test results. Serum Conventional Units (mg/dL urea N) System Mean Repeatability* Within Day** Within Lab*** Concentration SD CV % SD CV % SD CV % No. of Obs. 3 0.1 4.0 0.2 8.0 0.2 8.7 80 10 0.1 1.0 0.2 1.8 0.2 2.1 80 XT 7600 11 0.1 1.2 0.2 2.1 0.2 2.1 80 17 0.3 1.6 0.3 1.9 0.3 1.9 80 51 0.7 1.3 0.7 1.3 0.8 1.5 80 107 1.1 1.0 1.2 1.2 1.4 1.3 80 * Repeatability (formerly called within-run precision) was determined using two replicates per run. ** Within Day precision was determined using two runs per day with two replications per run. *** Within Lab precision was determined using a single lot of slides and a single calibration. No. of Days 20 20 20 20 20 20 SI Units (mmol/L urea) System Mean Repeatability* Concentration SD CV % Within Day** SD CV % Within Lab*** SD CV % 1.0 0.04 4.1 0.08 8.0 0.08 8.7 3.5 0.04 1.0 0.06 1.8 0.07 2.1 XT 7600 4.0 0.05 1.2 0.08 2.1 0.08 2.1 6.1 0.10 1.6 0.11 1.8 0.11 1.8 18.1 0.24 1.3 0.24 1.3 0.28 1.5 38.3 0.39 1.0 0.45 1.2 0.51 1.3 * Repeatability (formerly called within-run precision) was determined using two replicates per run. ** Within Day precision was determined using two runs per day with two replications per run. *** Within Lab precision was determined using a single lot of slides and a single calibration. No. of Obs. 80 80 80 80 80 80 No. of Days 20 20 20 20 20 20 10 of 29 Pub. No. J65403_EN Version 2.0 INSTRUCTIONS FOR USE Performance Characteristics UREA Urea Urine Conventional Units (mg/dL urea N) System Mean Concentration Repeatability* SD CV % Within Day** SD CV % Within Lab*** SD CV % 84 2.4 2.8 6.0 7.1 7.2 8.5 293 3.8 1.3 5.4 1.8 6.8 2.3 XT 7600 404 4.1 1.0 7.1 1.8 9.1 2.3 683 7.6 1.1 7.6 1.1 12.2 1.8 1453 14.0 1.0 19.5 1.3 19.5 1.3 2331 21.4 0.9 28.2 1.2 30.6 1.3 * Repeatability (formerly called within-run precision) was determined using two replicates per run. ** Within Day precision was determined using two runs per day with two replications per run. *** Within Lab precision was determined using a single lot of slides and a single calibration. No. of Obs. No. of Days 80 20 80 20 80 20 80 20 80 20 80 20 SI Units (mmol/L urea) System Mean Concentration Repeatability* SD CV % Within Day** SD CV % Within Lab*** SD CV % 30.0 0.85 2.8 2.13 7.1 2.55 8.5 104.6 1.36 1.3 1.92 1.8 2.44 2.3 XT 7600 144.1 243.9 1.47 1.0 2.53 1.8 3.25 2.3 2.70 1.1 2.73 1.1 4.35 1.8 518.4 5.00 1.0 6.95 1.3 6.95 1.3 832.1 7.65 0.9 10.06 1.2 10.93 1.3 * Repeatability (formerly called within-run precision) was determined using two replicates per run. ** Within Day precision was determined using two runs per day with two replications per run. *** Within Lab precision was determined using a single lot of slides and a single calibration. No. of Obs. No. of Days 80 20 80 20 80 20 80 20 80 20 80 20 Specificity Substances that Do Not Interfere Serum and Plasma The substances listed in the table below were tested with the UREA test within VITROS XT UREA-CREA Slides following CLSI EP0713,14 and found not to interfere, bias < 2.0 mg/dL (< 0.7 mmol/L) at 9 mg/dL (3.2 mmol/L) urea N and bias < 4.0 mg/dL (< 1.4 mmol/L) at 40 mg/dL (14.3 mmol/L) urea N at the concentration shown. Compound 5-Aminosalicylic acid 6-mercaptopurine Acetaminophen Alprazolam Amikacin Amlodipine besylate Ammonium chloride Amoxicillin Amphotericin B Ascorbic acid Atorvastatin calcium Benazepril -hydroxybutyrate Bilirubin, conjugated Bilirubin, unconjugated Calcium dobesilate Carbenicillin Cefazolin Cefoxitin Ceftriaxone Concentration 2.04 mg/dL 133 mol/L 0.2 mg/dL 13.1 mol/L 20 mg/dL 1324 mol/L 0.2 mg/dL 6.48 mol/L 14.4 mg/dL 246 mol/L 14 g/dL 245 nmol/L 5.35 mg/dL 1 mmol/L 7.53 mg/dL 206 mol/L 35.5 mg/dL 384 mol/L 60 mg/dL 3.42 mmol/L 69.3 mg/dL 600 Eq/L 2.04 mg/dL 48 mol/L 157 mg/dL 12.46 mmol/L 57.65 mg/dL 684 mol/L 40 mg/dL 684 mol/L 6 mg/dL 144 mol/L 1.43 mg/dL 37.8 mol/L 120 mg/dL 2643 mol/L 663 mg/dL 15.5 mmol/L 81 mg/dL 1460 mol/L Compound Hypaque (diatrizoate) Ibuprofen Insulin Intralipid Isoniazid Kanamycin L-pipecolic acid Levodopa Levothyroxine Lidocaine Lithium Acetoacetate Lovastatin Metformin Metronidazole N-Acetylcysteine Nafcillin Naproxen N-Ethyl glycine Nitrofurantoin Omeprazole Concentration 19.28 mg/dL 314 µmol/L 50 mg/dL 2425 µmol/L 3.12 µg/dL 5.38 nmol/L 2000 mg/dL 20 g/L 6 mg/dL 438 µmol/L 9 mg/dL 186 µmol/L 5.7 mg/dL 442 µmol/L 0.98 mg/dL 49.5 µmol/L 100 µg/dL 1.29 µmol/L 1.5 mg/dL 64 µmol/L 324 mg/dL 30 mmol/L 21 µg/dL 0.519 µmol/L 4.0 mg/dL 310 µmol/L 12.3 mg/dL 719 µmol/L 166.5 mg/dL 10.2 mmol/L 11.1 mg/dL 268 µmol/L 50 mg/dL 2170 µmol/L 0.53 mg/dL 51.2 µmol/L 0.4 mg/dL 16.8 µmol/L 0.84 mg/dL 24.3 µmol/L Version 2.0 Pub. No. J65403_EN 11 of 29 UREA Urea INSTRUCTIONS FOR USE Performance Characteristics Compound Cefuroxime Cephalothin Cholesterol Clindamycin (Cleocin) Cloxacillin Creatine Cyclosporin-a Dextran 40 Diphenhydramine Dipyrone (Metamizole) Dobutamine Dopamine Doxycycline Entecavir Ethambutol Ethamsylate Ethanol Flucytosine Furosemide Gadodiamide Gentamicin Gentisic acid Glipizide Glucose Glutathione Glyburide (Glybenclamide) Glycine ethyl ester Glycocyamidine Hemoglobin Concentration 60.1 mg/dL 1416 mol/L 180 mg/dL 4540 mol/L 500 mg/dL 13 mmol/L 5.1 mg/dL 120 mol/L 4.5 mg/dL 103.23 mol/L 9 mg/dL 707 mmol/L 0.563 mg/dL 4.69 mol/L 6 g/dL 60 g/L 0.50 mg/dL 19.6 mol/L 18 mg/dL 540 mol/L 121 g/dL 4.01 mol/L 90 g/dL 5.87 mol/L 3.0 mg/dL 67.5 mol/L 2.3 g/dL 0.083 mol/L 3 mg/dL 147 mol/L 6 mg/dL 228 mol/L 599 mg/dL 130 mmol/L 30 mg/dL 2.33 mmol/L 6 mg/dL 181 mol/L 86.0 mg/dL 1.5 mmol/L 3 mg/dL 62.8 mol/L 1.8 mg/dL 117 mol/L 0.30 mg/dL 6.73 mol/L 1000 mg/dL 56 mmol/L 92 mg/dL 3 mmol/L 0.192 mg/dL 3.89 mol/L 0.71 mg/dL 4.4 mg/dL 1000 mg/dL 51.2 mol/L 442 µmol/L 155 µmol/L Compound Oxycodone pH pH Phenobarbital Polymyxin B Polymyxin E (Colistin) Proline Propranolol Pseudoephedrine Pyruvate Rifampicin (Rifampin) Salicylic acid Sodium bicarbonate Spironolactone Streptomycin Sulbactam Sulfamethoxazole Sulfapyridine Sulfasalazine Tenofovir disoproxil Tetracycline Theophylline Tolazamide Tolbutamide Triglycerides Trimethoprim Uric acid Vancomycin Warfarin Concentration 0.05 mg/dL 1.59 µmol/L 6.8 6.8 8.8 8.8 69 mg/dL 2970 µmol/L 3.61 mg/dL 30 µmol/L 2.7 mg/dL 23.1 µmol/L 24 mg/dL 2.085 mmol/L 0.2 mg/dL 7.71 µmol/L 1 mg/dL 60.5 µmol/L 17.6 mg/dL 2 mmol/L 6.43 mg/dL 78.1 µmol/L 60 mg/dL 4.34 µmol/L 336 mg/dL 40 mmol/L 0.06 mg/dL 1.44 µmol/L 12.9 mg/dL 444 µmol/L 3 mg/dL 128.7 µmol/L 40 mg/dL 1.58 mmol/L 30 mg/dL 1200 µmol/L 30 mg/dL 754 µmol/L 177 g/dL 3.41 mol/L 2.4 mg/dL 54 µmol/L 6 mg/dL 333 µmol/L 40 mg/dL 1284 µmol/L 64.1 mg/dL 2.37 mmol/L 1500 mg/dL 16.9 mmol/L 4.2 mg/dL 145 µmol/L 23.5 mg/dL 12 mg/dL 7.5 mg/dL 1400 mmol/L 82.8 µmol/L 243 µmol/L Urine The substances listed in the table below were tested with the UREA test within VITROS UREA-CREA Slides following CLSI EP0713,14 and found not to interfere, bias < 90 mg/dL (< 32 mmol/L) at 900 mg/dL (321 mmol/L) urea N and bias < 140 mg/dL (< 50 mmol/L) at 1400 mg/dL (500 mmol/L) urea N at the concentration shown. 12 of 29 Pub. No. J65403_EN Version 2.0 INSTRUCTIONS FOR USE Performance Characteristics Compound Concentration 10% Thymol in isopropanol* 3.3 mL/L 3.3 mL/L Ammonium chloride 5.35 mg/dL 1 mmol/L Ascorbic acid 201 mg/dL 11.4 mmol/L Bilirubin, conjugated 57.65 mg/dL 684 µmol/L Bilirubin, unconjugated 40 mg/dL 684 µmol/L Creatine 131.1 mg/dL 10 mmol/L Hemoglobin 1000 mg/dL 155 µmol/L Intralipid 800 mg/dL 8 g/L Lithium Acetoacetate 324 mg/dL 30 mmol/L Magnesium chloride 571 mg/dL 60 mmol/L Pyruvate 17.6 mg/dL 2 mmol/L Rifampicin (Rifampin) 4.5 mg/dL 54.7 µmol/L Sodium bicarbonate 672 mg/dL 80 mmol/L Sodium fluoride* 5 g/L 119 mmol/L Sodium formate* 3.35 mg/dL 49.3 mmol/L Sodium oxalate 60 mg/dL 4.5 mmol/L Toluene* 1.3 mL/L 12.3 mmol/L Total Protein 50 mg/dL 0.5 g/L Uric acid 23.5 mg/dL * Substance is a common urine preservative 1400 µmol/L UREA Urea Version 2.0 Pub. No. J65403_EN 13 of 29 INSTRUCTIONS FOR USE CREA Test CREA Creatinine Rx ONLY Intended Use For in vitro diagnostic use only. The CREA test within the VITROS XT Chemistry Products UREA-CREA Slides quantitatively measures creatinine (CREA) concentration in serum, plasma, and urine using VITROS XT 7600 Integrated Systems. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes. Summary and Explanation of the Test Serum creatinine and urinary creatinine excretion is a function of lean body mass in normal persons and shows little or no response to dietary changes. The serum creatinine concentration is higher in men than in women. Since urinary creatinine is excreted mainly by glomerular filtration, with only small amounts due to tubular secretion, serum creatinine and a 24-hour urine creatinine excretion can be used to estimate the glomerular filtration rate. Serum creatinine is increased in acute or chronic renal failure, urinary tract obstruction, reduced renal blood flow, shock, dehydration, and rhabdomyolysis. Causes of low serum creatinine concentration include debilitation and decreased muscle mass. Exercise may cause an increased creatinine clearance. The creatinine clearance rate is unreliable if the urine flow is low. Principles of the Procedure The CREA test is a multilayered, analytical element coated on a polyester support. A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Creatinine diffuses to the reagent layer, where it is hydrolyzed to creatine in the rate-determining step. The creatine is converted to sarcosine and urea by creatine amidinohydrolase. The sarcosine, in the presence of sarcosine oxidase, is oxidized to glycine, formaldehyde, and hydrogen peroxide. The final reaction involves the peroxidase-catalyzed oxidation of a leuco dye to produce a colored product. Following addition of the sample, the slide is incubated. During the initial reaction phase, endogenous creatine in the sample is oxidized. The resulting change in reflection density is measured at 2 time points. The difference in reflection density is proportional to the concentration of creatinine present in the sample. Test Type and Conditions Test Type VITROS System* Approximate Incubation Time Temperature Two-point rate XT 7600 5.0 minutes 37 °C (98.6 °F) * Not all products and systems are available in all countries. Wavelength 670 nm Reaction Sample Volume 3.2 L Reaction Scheme creatinine + H2O creatinine amidohydrolase creatine creatine + H2O creatine amidinohydrolase sarcosine + urea sarcosine + O2 + H2O sarcosine oxidase glycine + formaldehyde + H2O2 H2O2 + leuco dye peroxidase dye + 2H2O Version 2.0 Pub. No. J65403_EN 14 of 29 INSTRUCTIONS FOR USE Warnings and Precautions CREA Creatinine Warnings and Precautions For in vitro diagnostic use only. WARNING: Take care when handling materials and samples of human origin. Since no test method can offer complete assurance that infectious agents are absent, consider all clinical specimens, controls, and calibrators potentially infectious. Handle specimens, solid and liquid waste, and test components in accordance with local regulations and CLSI Guideline M292 or other published biohazard safety guidelines. For specific warnings and precautions for calibrators, quality control materials, and other components, refer to the Instructions for Use for the appropriate VITROS product, or to other manufacturer's product literature. Reagents Slide Ingredients Reactive Ingredients per cm2 Creatinine amidohydrolase (Flavobacterium sp.,) 0.20 U; creatine amidinohydrolase (Alcaligenes sp.,) 3.6 U; sarcosine oxidase (Bacillus sp.) 0.55 U; peroxidase (horseradish root) 1.6 U and 2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis(4dimethylaminophenyl) imidazole (leuco dye) 32 µg. Other Ingredients Pigment, binders, surfactants, stabilizer, scavenger, chelator, buffer, dye solubilizer and cross-linking agent. Slide Diagram 1. Upper slide mount 2. Spreading layer (TiO2) 3. Reagent layer · creatinine amidohydrolase · creatine amidinohydrolase · sarcosine oxidase · peroxidase · leuco dye · buffer, pH 7.0 4. Support layer 5. Lower slide mount Reagent Handling Caution: Do not use slide cartridges with damaged or incompletely sealed packaging. · Inspect the packaging for signs of damage. · Be careful when opening the outer packaging with a sharp instrument so as to avoid damage to the individual product packaging. Reagent Preparation IMPORTANT: The slide cartridge must reach room temperature, 1828 °C (6482 °F), before it is unwrapped and loaded into the slide supply. 1. Remove the slide cartridges from storage. 2. Warm the wrapped cartridge at room temperature for 30 minutes when taken from the refrigerator or 60 minutes from the freezer. 3. Unwrap and load the cartridge into the slide supply. Note: Load the cartridges within 24 hours after they reach room temperature, 1828 °C (6482 °F). Reagent Storage and Stability VITROS XT UREA-CREA Slides are stable until the expiration date on the carton when they are stored and handled as specified. Do not use beyond the expiration date. Reagent Unopened Opened Refrigerated Frozen On-analyzer On-analyzer Storage Condition 28 °C (3646 °F) -18 °C ( 0 °F) System turned on System turned off Stability 4 weeks Until expiration date 2 weeks 2 hours · Do not store with or near ammonia, ammonia compounds, or amines. · Verify performance with quality control materials: If the system is turned off for more than 2 hours. After reloading cartridges that have been removed from the slide supply and stored for later use. Version 2.0 Pub. No. J65403_EN 15 of 29 CREA Creatinine INSTRUCTIONS FOR USE Specimen Collection, Preparation and Storage Specimen Collection, Preparation and Storage Specimens Recommended · Serum · Plasma: Heparin (lithium and sodium) · Urine IMPORTANT: Certain collection devices have been reported to affect other analytes and tests.3 Owing to the variety of specimen collection devices available, Ortho Clinical Diagnostics is unable to provide a definitive statement on the performance of its products with these devices. Confirm that your collection devices are compatible with this test. Specimens Not Recommended Do not use specimens obtained through catheters used to infuse hyperalimentation fluid. Refer to "Limitations of the Procedure." Serum and Plasma Specimen Collection and Preparation Collect specimens using standard laboratory procedures.5,6 Note: For details on minimum fill volume requirements, refer to the operating instructions for your system. Patient Preparation No special patient preparation is necessary. Special Precautions Centrifuge specimens and remove the serum or plasma from the cellular material within 4 hours of collection.4 Specimen Handling and Storage · Handle and store specimens in stoppered containers to avoid contamination and evaporation. · Mix samples by gentle inversion and bring to room temperature, 1828 °C (6482 °F), prior to analysis. Specimen Storage and Stability: Serum and Plasma Storage Room temperature Refrigerated Frozen Temperature 1828 °C (6482 °F) 28 °C (3646 °F) -18 °C ( 0 °F) Stability 5 days 30 days 6 months Urine Specimen Collection and Preparation · Collect specimens using standard laboratory procedures.7 · Keep refrigerated until analysis. Note: For details on minimum fill volume requirements, refer to the operating instructions for your system. Patient Preparation No special patient preparation is necessary. Special Precautions Urine specimens must be pretreated prior to processing. Refer to "Specimen Pretreatment" for instructions. Specimen Handling and Storage · Handle and store specimens in stoppered containers to avoid contamination and evaporation. · Mix samples by gentle inversion and bring to room temperature, 1828 °C (6482 °F), prior to analysis. 16 of 29 Pub. No. J65403_EN Version 2.0 INSTRUCTIONS FOR USE Specimen Pretreatment Specimen Storage and Stability: Urine Storage Room temperature Refrigerated Frozen Temperature 1828 °C (6482 °F) 28 °C (3646 °F) -18 °C ( 0 °F) Stability 3 days 5 days 6 months CREA Creatinine Specimen Pretreatment Urine Predilution Pretreatment is managed by the analyzer, no operator intervention is required. Testing Procedure Materials Provided VITROS XT Chemistry Products UREA-CREA Slides Materials Required but Not Provided · VITROS Chemistry Products Calibrator Kit 1 · Quality control materials, such as VITROS Chemistry Products Performance Verifier I and II for serum and plasma · VITROS Chemistry Products 7% BSA · Reagent-grade water · VITROS Chemistry Products FS Diluent Pack 2 (BSA/Saline) (for on-analyzer dilution of serum and plasma samples) · VITROS Chemistry Products FS Diluent Pack 3 (Specialty Diluent/Water) (for on-analyzer dilution of urine samples) Operating Instructions · Check reagent inventories at least daily to ensure that quantities are sufficient for the planned workload. · For additional information, refer to the operating instructions for your system. IMPORTANT: Bring all fluids and samples to room temperature, 1828 °C (6482 °F), prior to analysis. Sample Dilution Serum and Plasma If creatinine concentrations exceed the system's measuring (reportable or dynamic) range or if the analyzer displays a DP code (indicating high background density, usually due to an elevated creatine concentration): On-Analyzer Sample Dilution Refer to the operating instructions for your system for more information on the On-Analyzer Dilution Procedure. For VITROS XT 7600 Integrated Systems, use VITROS Chemistry Products FS Diluent Pack 2 for the dilution. Manual Sample Dilution 1. Dilute the sample with 1 part sample and 1 part VITROS 7% BSA. 2. Reanalyze. 3. Multiply the results by 2 to obtain an estimate of the original sample's creatinine concentration. Urine If creatinine concentrations exceed the system's measuring (reportable or dynamic) range: On-Analyzer Sample Dilution Refer to the operating instructions for your system for more information on the On-Analyzer Dilution Procedure. For VITROS XT 7600 Integrated Systems, use VITROS Chemistry Products FS Diluent Pack 3 for the dilution. Manual Sample Dilution 1. Dilute the sample with 1 part sample and 1 part reagent-grade water. 2. Reanalyze. 3. Multiply the results by 2 to obtain an estimate of the original sample's creatinine concentration. Version 2.0 Pub. No. J65403_EN 17 of 29 CREA Creatinine INSTRUCTIONS FOR USE Calibration Calibration Required Calibrators VITROS Chemistry Products Calibrator Kit 1 Note: The same VITROS Calibrator Kit is used to calibrate serum, plasma, and urine creatinine. However, specific supplementary assigned values (SAVs) are applied for each body fluid. Calibrator Preparation, Handling, and Storage Refer to the Instructions for Use for VITROS Calibrator Kit 1. Calibration Procedure Refer to the operating instructions for your system. When to Calibrate Calibrate: · When the slide lot number changes. · When critical system parts are replaced due to service or maintenance. · When government regulations require. For example, in the USA, CLIA regulations require calibration or calibration verification at least once every six months. The CREA test within the VITROS XT UREA-CREA Slides may also need to be calibrated: · If quality control results are consistently outside acceptable range. · After certain service procedures have been performed. For additional information, refer to the operating instructions for your system. Calculations Reflectance from the slide is read at 670 nm at two fixed time points during the incubation period, and the change in reflectance between these two readings is calculated. Once a calibration has been performed for each slide lot, creatinine concentration in unknown samples can be determined using the software-resident two-point rate math model and the change in reflectance calculated for each unknown test slide. Validity of a Calibration Calibration parameters are automatically assessed by the system against a set of quality parameters detailed in Review Assay Data screen on VITROS XT Integrated Systems. Failure to meet any of the pre-defined quality parameters results in a failed calibration. The calibration report should be used in conjunction with quality control results to determine the validity of a calibration. Measuring (Reportable or Dynamic) Range Fluid Conventional Units (mg/dL) Serum/Plasma 0.1514.0 Urine* 3.2346.5 * After multiplying by a dilution factor of 21. SI Units (mol/L) 131238 28330631 Alternate Units (mg/L) 1.5140 323465 For out-of-range samples, refer to "Sample Dilution." Traceability of Calibration The values assigned to the VITROS Chemistry Products Calibrator Kit 1 for Creatinine are traceable to a Gas Chromatography Isotope Dilution Mass Spectrometry (GC/IDMS) method21 and National Institute of Standards and Technology (NIST) SRM® 914 creatinine standard reference material. Quality Control Quality Control Material Selection IMPORTANT: VITROS Performance Verifiers are recommended for use with VITROS XT Integrated Systems. Evaluate the performance of other commercial control fluids for compatibility with this test before using for quality control. 18 of 29 Pub. No. J65403_EN Version 2.0 INSTRUCTIONS FOR USE Results CREA Creatinine · Controls that are reconstituted with deionized water should perform acceptably. · Control materials other than VITROS Performance Verifiers may show a difference when compared with other creatinine methods if they: Depart from a true human matrix. Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives. · Liquid serum and urine controls often contain high creatine levels and may give DP codes. · Do not use control materials stabilized with ethylene glycol. Urine For urine specimens, use commercially available urine control materials. IMPORTANT: If using a VITROS XT Integrated Systems in On-Analyzer Dilution Mode, do not manually dilute samples for analysis and do not multiply by a dilution factor after analysis. Refer to the operating instructions for your system for more information on the On-Analyzer Dilution Procedure. Quality Control Procedure Recommendations · Choose control levels that check the clinically relevant range. · Analyze quality control materials in the same manner as patient samples, before or during patient sample processing. · To verify system performance, analyze control materials: After calibration. According to local regulations or at least once each day that the test is being performed. After specified service procedures are performed. Refer to the operating instructions for your system. · If control results fall outside your acceptable range, investigate the cause before deciding whether to report patient results. · For general quality control recommendations, refer to Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Fourth Edition 11 or other published guidelines. · For additional information, refer to the operating instructions for your system. Quality Control Material Preparation, Handling, and Storage Refer to the Instructions for Use for VITROS Chemistry Products Performance Verifier I and II or to other manufacturer's product literature. Results Reporting Units and Unit Conversion The VITROS XT Systems may be programmed to report CREA results in conventional, SI, and alternate units. Conventional Units mg/dL SI Units µmol/L (mg/dL x 88.4) Alternate Units mg/L (mg/dL x 10) Limitations of the Procedure Known Interferences Serum and Plasma · Creatine: At a creatinine concentration of 1.5 mg/dL (133 mol/L), creatine greater than 8 mg/dL (707 mol/L) will be flagged with a DP code (because highly elevated creatine concentrations may cause excessive background density). For unflagged samples, residual bias because of creatine will be less than 0.15 mg/dL (13 mol/L). At a creatinine concentration of 14 mg/dL (1237 mol/L), creatine greater than 1 mg/dL (88 mol/L) will be flagged with a DP code. Residual bias for unflagged samples will be less than 2%. Refer to "Sample Dilution" for dilution instructions. · Proline: Patients receiving hyperalimentation fluids containing proline may show an increase of 0.2 mg/dL (18 mol/L). Do not collect specimens from intravenous fluid lines contaminated with hyperalimentation fluid. The VITROS XT Chemistry Products UREA-CREA Slides method was screened for interfering substances following CLSI EP07.13 ,14The substances listed in the table, when tested at the concentrations indicated, caused the bias shown. For substances that were tested and did not interfere, refer to "Specificity." Version 2.0 Pub. No. J65403_EN 19 of 29 CREA Creatinine INSTRUCTIONS FOR USE Expected Values Interferent Concentration Creatinine Concentration Bias** Interferent* Conv. Units SI Units Conv. Units (mg/dL) SI Units (mol/L) Conv. Units (mg/dL) SI Units (mol/L) Bilirubin, conjugated 58 mg/dL 684 mol/L 1.6 140 -0.16 -14 Dipyrone 9 mg/dL 270 mol/L 1.6 144 -0.20 -18 (Metamizole)*** 14 mg/dL 405 mol/L 4.9 434 -0.73 -64 Ethamsylate 4.1 mg/dL 156 mol/L 1.7 152 -0.18 -16 Glutathione 69 mg/dL 2.25 mmol/L 1.6 144 -0.23 -20 N-Ethyl glycine**** 0.40 mg/dL 38 mmol/L 1.7 147 0.21 18 Proline 18 mg/dL 1564 mol/L 1.7 152 0.24 21 1.6 138 -0.24 -21 Tolazamide 5.0 mg/dL 161 mol/L 4.6 409 -0.55 -49 15 g/dL 150 g/L 1.7 151 0.26 23 Total protein 12 g/dL 120 g/L 5.0 439 0.53 47 * It is possible that other interfering substances may be encountered. These results are representative; however, your results may differ somewhat due to test-to-test variation. The degree of interference at concentrations other than those listed might not be predictable. ** The bias is an estimate of the maximum bias observed. *** Dipyrone at 9 mg/dL is equivalent to 6X the equivalent of a 1000 mg oral dose, or 1.5X the equivalent of a 1000 mg intravenous dose.22 **** N-ethyl glycine is a metabolite of lidocaine and may be present at high levels in patients on long-term lidocaine therapy.23 Other Limitations Certain drugs and clinical conditions are known to alter creatinine concentration in vivo. For additional information, refer to one of the published summaries.15,16 Expected Values IMPORTANT: If using results to calculate an estimated glomerular filtration rate (eGFR), confirm that you are using the appropriate MDRD (Modification of Diet in Renal Disease) equation.24 Reference Interval The serum reference intervals are the central 95% of results from an external study of apparently healthy adults (serum: 180 males and 180 females). The urine reference intervals are based on a separate external study.25 Serum Male Female Urine Male Female Conventional Units 0.661.25 mg/dL 0.521.04 mg/dL 10002000 mg/day* 8001800 mg/day* SI Units Alternate Units 58110 µmol/L 4692 µmol/L 6.612.5 mg/L 5.210.4 mg/L 884017680 µmol/day** 10002000 mg/day*** 707215912 µmol/day** 8001800 mg/day*** * Creatinine concentration (mg/dL) x 24-hour volume (dL) = mg/day. ** Creatinine concentration (µmol/L) x 24-hour volume (L) = µmol/day. *** Creatinine concentration (mg/L) x 24-hour volume (L) = mg/day. Each laboratory should confirm the validity of these intervals for the population it serves. Performance Characteristics Detection Capability The Limit of Quantitation (LoQ) for the CREA test within the VITROS XT UREA-CREA Slides is 0.15 mg/dL for serum/ plasma and 3.2 mg/dL for urine. The total number of LoQ determinations was 72 for serum and 64 for urine. The LoQ was established consistent with CLSI EP17.18 20 of 29 Pub. No. J65403_EN Version 2.0 INSTRUCTIONS FOR USE Performance Characteristics CREA Creatinine Fluid Type LoQ* Conventional Units mg/dL Serum/Plasma 0.15 Urine 3.2 * The Total Error goal used to accept the LoQ was 0.06 mg/dL for serum and 1.2 mg/dL for urine. SI Units mol/L 13 283 Method Comparison The plots and tables below show the results of a method comparison study with serum samples and urine samples analyzed on the VITROS XT 7600 Integrated System and with the Ortho Clinical Diagnostics comparative method (an HPLC method),26 which has demonstrated equivalence to the Gas Chromatography Isotope Dilution Mass Spectrometry (GC/IDMS) reference method. The tables also show the results of comparisons with serum and urine samples between the VITROS XT 7600 Integrated System and the VITROS Chemistry Products CREA Slides on a VITROS 5600 Integrated System. Testing followed CLSI EP09.19 Serum Conventional Units SI Units VITROS XT 7600 System (mg/dL) VITROS XT 7600 System (µmol/L) Comparative Method: HPLC (mg/dL) Comparative Method: HPLC (mol/L) Conventional Units (mg/dL) SI Units (µmol/L) Correlation Range of Range of n Slope Coefficient Sample Conc. Intercept Sy.x Sample Conc. Intercept Sy.x XT 7600 vs. Comparative Method 130 1.01 0.999 0.2613.40 -0.01 0.21 231185 -0.48 18.54 XT 7600 vs. 5600 130 1.00 1.000 0.20 13.49 -0.01 0.09 171193 -0.65 8.16 Comparisons made using the same patient samples tested with the VITROS Chemistry Products CREA Slides run on the VITROS 5600 Integrated System. Version 2.0 Pub. No. J65403_EN 21 of 29 CREA Creatinine Urine Conventional Units INSTRUCTIONS FOR USE Performance Characteristics SI Units VITROS XT 7600 System (mg/dL) VITROS XT 7600 System (µmol/L) Comparative Method: HPLC (mg/dL) Comparative Method: HPLC (mol/L) Conventional Units (mg/dL) SI Units (µmol/L) Correlation Range of Range of n Slope Coefficient Sample Conc. Intercept Sy.x Sample Conc. Intercept Sy.x XT 7600 vs. Comparative Method 116 1.01 0.999 13.6336.6 -0.83 4.30 120729758 -73.45 380.12 XT 7600 vs. 5600 116 1.01 0.998 13.0336.6 -0.93 5.36 115129751 -82.54 474.18 Comparisons made using the same patient samples tested with the VITROS Chemistry Products CREA Slides run on the VITROS 5600 Integrated System. Precision Precision was evaluated with patient pools and quality control materials on the VITROS XT 7600 Integrated System following CLSI EP05.20 The data presented are a representation of test performance and are provided as a guideline. Variables such as sample handling and storage, reagent handling and storage, laboratory environment and system maintenance can affect reproducibility of test results. Serum Conventional Units (mg/dL) System Mean Concentration Repeatability* SD CV % Within Day** SD CV % Within Lab*** SD CV % 0.66 0.007 1.1 0.008 1.2 0.011 1.7 0.85 0.010 1.2 0.012 1.4 0.014 1.6 XT 7600 0.86 0.012 1.4 0.012 1.4 0.014 1.6 5.41 0.030 0.6 0.040 0.7 0.084 1.6 9.41 0.068 0.7 0.072 0.8 0.163 1.7 12.62 0.090 0.7 0.107 0.8 0.220 1.7 * Repeatability (formerly called within-run precision) was determined using two replicates per run. ** Within Day precision was determined using two runs per day with two replications per run. *** Within Lab precision was determined using a single lot of slides and a single calibration. No. of Obs. 80 80 80 80 80 80 No. of Days 20 20 20 20 20 20 22 of 29 Pub. No. J65403_EN Version 2.0 INSTRUCTIONS FOR USE Performance Characteristics CREA Creatinine SI Units (mol/L) System Mean Concentration Repeatability* SD CV % Within Day** SD CV % Within Lab*** SD CV % 58 0.6 1.0 0.7 1.1 1.0 1.6 75 0.9 1.2 1.0 1.3 1.3 1.7 XT 7600 76 1.1 1.4 1.1 1.4 1.2 1.6 478 2.6 0.5 3.5 0.7 7.4 1.6 831 6.0 0.7 6.4 0.8 14.4 1.7 1116 7.9 0.7 9.4 0.8 19.4 1.7 * Repeatability (formerly called within-run precision) was determined using two replicates per run. ** Within Day precision was determined using two runs per day with two replications per run. *** Within Lab precision was determined using a single lot of slides and a single calibration. No. of Obs. 80 80 80 80 80 80 No. of Days 20 20 20 20 20 20 Urine Conventional Units (mg/dL) System Mean Concentration Repeatability* SD CV % Within Day** SD CV % Within Lab*** SD CV % 39.0 0.26 0.7 0.37 1.0 0.52 1.3 58.5 0.67 1.1 0.90 1.5 1.14 2.0 XT 7600 137.5 1.47 1.1 2.20 1.6 3.15 2.3 239.4 2.13 0.9 2.27 0.9 3.13 1.3 317.2 2.00 0.6 4.13 1.3 5.44 1.7 * Repeatability (formerly called within-run precision) was determined using two replicates per run. ** Within Day precision was determined using two runs per day with two replications per run. *** Within Lab precision was determined using a single lot of slides and a single calibration. No. of Obs. 80 80 80 80 80 No. of Days 20 20 20 20 20 SI Units (mol/L) System Mean Concentration Repeatability* SD CV % Within Day** SD CV % Within Lab*** SD CV % 3446 23 0.7 33 1.0 46 1.3 5169 59 1.1 79 1.5 101 2.0 XT 7600 12156 130 1.1 194 1.6 279 2.3 21161 188 0.9 200 0.9 277 1.3 28042 176 0.6 365 1.3 481 1.7 * Repeatability (formerly called within-run precision) was determined using two replicates per run. ** Within Day precision was determined using two runs per day with two replications per run. *** Within Lab precision was determined using a single lot of slides and a single calibration. No. of Obs. 80 80 80 80 80 No. of Days 20 20 20 20 20 Specificity Substances that Do Not Interfere Serum and Plasma The substances listed in the table below were tested with the CREA test within VITROS XT UREA-CREA Slides following CLSI EP0713,14 and found not to interfere, bias < 0.13 mg/dL (< 11.8 mol/L) at 1.5 mg/dL (132.6 mol/L) and bias < 0.44 mg/dL (< 39.2 mol/L) at 5 mg/dL (442.0 mol/L), at the concentration shown. Compound 5-Aminosalicylic acid 6-mercaptopurine Acetaminophen Alprazolam Amikacin Amlodipine besylate Ammonium chloride Amoxicillin Amphotericin B Concentration 2.04 mg/dL 133 mol/L 0.2 mg/dL 13.1 mol/L 20 mg/dL 1324 mol/L 0.2 mg/dL 6.48 mol/L 14.4 mg/dL 246 mol/L 14 g/dL 245 nmol/L 5.35 mg/dL 1 mmol/L 7.53 mg/dL 206 mol/L 35.5 mg/dL 384 mol/L Compound Ibuprofen Insulin Intralipid Isoniazid Kanamycin L-pipecolic acid Levodopa Levothyroxine Lidocaine Concentration 50 mg/dL 2425 µmol/L 3.12 µg/dL 5.38 nmol/L 2000 mg/dL 20 g/L 6 mg/dL 438 µmol/L 9 mg/dL 186 µmol/L 5.7 mg/dL 442 µmol/L 0.98 mg/dL 49.5 µmol/L 100 µg/dL 1.29 µmol/L 1.5 mg/dL 64 µmol/L Version 2.0 Pub. No. J65403_EN 23 of 29 CREA Creatinine INSTRUCTIONS FOR USE Performance Characteristics Compound Ascorbic acid Atorvastatin calcium Benazepril -hydroxybutyrate Bilirubin, unconjugated Calcium dobesilate Carbenicillin Cefazolin Cefoxitin Ceftriaxone Cefuroxime Cephalothin Cholesterol Clindamycin (Cleocin) Cloxacillin Cyclosporin-a Dextran 40 Diphenhydramine Dobutamine Dopamine Doxycycline Entecavir Ethambutol Ethanol Flucytosine Furosemide Gadodiamide Gentamicin Gentisic acid Glipizide Glucose Glyburide (Glybenclamide) Glycine ethyl ester Glycocyamidine Hemoglobin Hypaque (diatrizoate) Concentration 60 mg/dL 3.42 mmol/L 69.3 mg/dL 600 Eq/L 2.04 mg/dL 48 mol/L 157 mg/dL 12.46 mmol/L 40 mg/dL 684 mol/L 6 mg/dL 1.43 mg/dL 120 mg/dL 663 mg/dL 81 mg/dL 60.1 mg/dL 180 mg/dL 500 mg/dL 5.1 mg/dL 4.5 mg/dL 0.563 mg/dL 6 g/dL 0.50 mg/dL 121 g/dL 90 g/dL 3.0 mg/dL 2.3 g/dL 3 mg/dL 599 mg/dL 30 mg/dL 6 mg/dL 86.0 mg/dL 3 mg/dL 1.8 mg/dL 0.30 mg/dL 1000 mg/dL 144 µmol/L 37.8 mol/L 2643 mol/L 15.5 mmol/L 1460 mol/L 1416 mol/L 4540 mol/L 13 mmol/L 120 mol/L 103.23 mol/L 4.69 mol/L 60 g/L 19.6 mol/L 4.01 mol/L 5.87 mol/L 67.5 mol/L 0.083 mol/L 147 mol/L 130 mmol/L 2.33 mmol/L 181 mol/L 1.5 mmol/L 62.8 mol/L 117 mol/L 6.73 mol/L 56 mmol/L 0.192 mg/dL 3.89 mol/L 0.71 mg/dL 4.4 mg/dL 1000 mg/dL 19.28 mg/dL 51.2 mol/L 442 µmol/L 155 µmol/L 314 mol/L Compound Lithium Acetoacetate Lovastatin Metformin Metronidazole N-Acetylcysteine Nafcillin Naproxen Nitrofurantoin Omeprazole Oxycodone pH pH Phenobarbital Polymyxin B Polymyxin E (Colistin) Propranolol Pseudoephedrine Pyruvate Rifampicin (Rifampin) Salicylic acid Sodium bicarbonate Spironolactone Streptomycin Sulbactam Sulfamethoxazole Sulfapyridine Sulfasalazine Tenofovir disoproxil Tetracycline Theophylline Tolbutamide Triglycerides Trimethoprim Uric acid Vancomycin Warfarin Concentration 324 mg/dL 30 mmol/L 21 µg/dL 0.519 µmol/L 4.0 mg/dL 310 µmol/L 12.3 mg/dL 719 µmol/L 15 mg/dL 0.92 mmol/L 11.1 mg/dL 50 mg/dL 0.4 mg/dL 0.84 mg/dL 0.05 mg/dL 6.8 8.8 69 mg/dL 3.61 mg/dL 2.7 mg/dL 0.2 mg/dL 1 mg/dL 17.6 mg/dL 4.8 mg/dL 60 mg/dL 336 mg/dL 0.06 mg/dL 12.9 mg/dL 3 mg/dL 40 mg/dL 30 mg/dL 30 mg/dL 177 g/dL 2.4 mg/dL 6 mg/dL 64.1 mg/dL 268 µmol/L 2170 µmol/L 16.8 µmol/L 24.3 µmol/L 1.59 µmol/L 6.8 8.8 2970 µmol/L 30 µmol/L 23.1 µmol/L 7.71 µmol/L 60.5 µmol/L 2 mmol/L 58.6 mol/L 4.34 µmol/L 40 mmol/L 1.44 µmol/L 444 µmol/L 128.7 µmol/L 1.58 mmol/L 1200 µmol/L 754 µmol/L 3.41 mol/L 54 µmol/L 333 µmol/L 2.37 mmol/L 1500 mg/dL 16.9 mmol/L 4.2 mg/dL 23.5 mg/dL 12 mg/dL 7.5 mg/dL 145 µmol/L 1400 mmol/L 82.8 µmol/L 243 µmol/L Urine The substances listed in the table below were tested with the CREA test within VITROS XT UREA-CREA Slides following CLSI EP0713 ,14 and found not to interfere, bias< 5.8 mg/dL (< 511 mol/L) at 60 mg/dL (5304 mol/L) and bias < 17 mg/dL (< 1503 mol/L) at 200 mg/dL (17680 mol/L) , at the concentration shown. Compound 10% Thymol in isopropanol* 12N Hydrochloric acid* Ammonium chloride Ascorbic acid Bilirubin, conjugated Bilirubin, unconjugated Boric acid* Concentration 3.3 mL/L 6.7 mL/L 5.35 mg/dL 201 mg/dL 57.65 mg/dL 40 mg/dL 5.3 mg/mL 3.3 mL/L 6.7 mL/L 1 mmol/L 11.4 mmol/L 684 µmol/L 684 µmol/L 85.7 mmol/L 24 of 29 Pub. No. J65403_EN Version 2.0 INSTRUCTIONS FOR USE Performance Characteristics Compound Concentration Boric acid/Sodium formate 5.3 mg/mL 85.7 mmol/L (combined)* 3.35 mg/mL 49.3 mmol/L Creatine 131.1 mg/dL 10 mmol/L Glacial Acetic Acid* 10 mL/L 10 mL/L Hemoglobin 1000 mg/dL 155 µmol/L Intralipid 800 mg/dL 8 g/L Lithium Acetoacetate 324 mg/dL 30 mmol/L Magnesium chloride 571 mg/dL 60 mmol/L Pyruvate 17.6 mg/dL 2 mmol/L Rifampicin (Rifampin) 4.5 mg/dL 54.7 µmol/L Sodium bicarbonate 672 mg/dL 80 mmol/L Sodium fluoride* 5 g/L 119 mmol/L Sodium formate* 3.35 mg/mL 49.3 mmol/L Sodium oxalate 60 mg/dL 4.5 mmol/L Toluene* 1.3 mL/L 12.3 mmol/L Total Protein 50 mg/dL 0.5 g/L Uric acid 23.5 mg/dL 1400 µmol/L * Substance is a common urine preservative CREA Creatinine Version 2.0 Pub. No. J65403_EN 25 of 29 UREA-CREA Urea/Creatinine INSTRUCTIONS FOR USE References References 1. Tietz NW (ed). Fundamentals of Clinical Chemistry. ed. 3. Philadelphia: WB Saunders; 967; 1987. 2. CLSI. Protection of Laboratory Workers from Occupationally Acquired Infections; Approved Guideline - Fourth Edition. CLSI document M29-A4. Wayne, PA: Clinical and Laboratory Standards Institute; 2014. 3. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988. 4. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield, IL: College of American Pathologists; 1992. 5. CLSI. Collection of Diagnostic Venous Blood Specimens. 7th ed. CLSI standard GP41. Wayne, PA: Clinical and Laboratory Standards Institute; 2017. 6. CLSI. Procedures and Devices for the Collection of Diagnostic Capillary Blood Specimens; Approved Standard Sixth Edition. CLSI document GP42-A6. Wayne, PA: Clinical and Laboratory Standard Institute; 2008. 7. CLSI. Urinalysis; Approved Guideline Third Edition. CLSI Document GP16-A3.Wayne, PA: Clinical and Laboratory Standards Institute; 2009. 8. Sampson EJ, et al. A coupled-enzyme equilibrium method for measuring urea in serum: optimization and evaluation of the AACC study group on urea candidate reference method. Clin. Chem. 1980; 26:816-26. 9. Knoll E, Hafner F, Dettmer K, Wisser H. The Determination of Calcium, Glucose, Urea, and Uric Acid Using the Kodak EKTACHEM Multilayer Film Technology: An Evaluation. J. Clin. Chem. Clin. Biochem. 20:491-498; 1982. 10. Libeer JC, Cooreman W, Theunis L. Factitiously Low Recoveries of Urea in Control Sera by the Kodak Ektachem Method. Clin. Chem. 40:494-495; 1994 11. CLSI. Statistical Quality Control for Quantitative Measurements Procedures: Principles and Definitions. Fourth Edition. CLSI guideline C24, Wayne, PA: Clinical and Laboratory Standards Institute; 2016. 12. Tietz NW (ed). Fundamentals of Clinical Chemistry. ed. 3. Philadelphia: WB Saunders; 676679; 1987. 13. CLSI. Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: Clinical and Laboratory Standards Institute; 2018. 14. CLSI. Supplemental Tables for Interference Testing in Clinical Chemistry. 1st ed. CLSI. CLSI supplement EP37. Wayne, PA: Clinical and Laboratory Standards Institute; 2018. 15. Young DS. Effects of Drugs on Clinical Laboratory Tests. ed. 4. Washington D.C.: AACC Press; 1995. 16. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990. 17. Rock RC, Walker WG, Jennings CD. Nitrogen Metabolites and Renal Function. In Tietz NW (ed). Fundamentals of Clinical Chemistry. ed 3. 669-700. 18. CLSI. Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline Second Edition. CLSI document EP 17-A2. Wayne, PA: Clinical and Laboratory Standards Institute; 2012. 19. CLSI. Measurement Procedure Comparison and Bias Estimation Using Patient Samples. 3rd ed. CLSI guideline EP09c. Wayne, PA: Clinical and Laboratory Standards Instituted; 2018. 20. CLSI. Evaluation of Precision Performance of Quantitative Measurement Procedures; Approved Guideline--Third Edition. CLSI document EP05-A3 [ISBN 1-56238-968-8]. CLSI, 940 West Valley Road, Wayne, PA 19087-1898 USA; 2014. 21. Siekmann L. Measurement of creatinine in human serum by isotope dilution mass spectrometry. J Clin Chem Clin Biochem 23:137144; 1985. 22. Bagnoud M-A, Reymond J-Ph. Interference of Metamizol (Dipyrone) on the Determination of Creatinine with the Kodak Dry Chemistry Slide Comparison with the Enzymatic Method from Boehringer. Eur. J. Clin. Chem. Clin. Biochem. 31: 753757; 1993. 23. Sena SF, Syed D, Romeo R, Krzymowski GA, McComb RB. Lidocaine Metabolite and Creatinine Measurements in the Ektachem 700: Steps to Minimize its Impact on Patient Care. Clin. Chem. 34:10; 1988. 24. National Kidney Disease Education Program. http://www.nkdep.nih.gov 25. McPherson R, Pincus M (eds.). Henry's Clinical Diagnostics and Management by Laboratory Methods, 21st edition. Philadelphia: Saunders Elsevier [ISBN-13: 978-1-4160-0287-1; 1410; 2006. 26. Ambrose RT, Ketchum DF, Smith JW. Creatinine Determined by "High Performance" Liquid Chromatography. Clin. Chem. 29: 256-259; 1983. 26 of 29 Pub. No. J65403_EN Version 2.0 INSTRUCTIONS FOR USE Glossary of Symbols Glossary of Symbols UREA-CREA Urea/Creatinine Version 2.0 Pub. No. J65403_EN 27 of 29 UREA-CREA Urea/Creatinine INSTRUCTIONS FOR USE Revision History Revision History Date of Revision 2019-01-17 Version 2.0 Description of Technical Changes* · Initial implementation in US · Updated (UREA-CREA): Intended Use- Revised for clarity Specimen Type- Added lithium and sodium Sample Dilution- Manual Sample Dilution instructions updated for Serum/ Plasma and Urine Limitations of the Procedure- Interferents Removed and Interferents Values updated in Serum/Plasma Table Specificity- Bias Statement updated for Serum/Plasma and Urine, compounds added and concentration values updated in Serum/Plasma Table References Removed · Updated (UREA): pH and Bias information removed from "Other Limitations" 2018-08-16 1.0 · Implemented for outside the US Only · Initial version of Instructions for Use * The change bars indicate the position of a technical amendment to the text with respect to the previous version of the document. When this Instructions For Use is replaced, sign and date below and retain as specified by local regulations or laboratory policies, as appropriate. Signature Obsolete Date 28 of 29 Pub. No. J65403_EN Version 2.0 INSTRUCTIONS FOR USE Revision History UREA-CREA Urea/Creatinine Ortho-Clinical Diagnostics Felindre Meadows Pencoed Bridgend CF35 5PZ United Kingdom Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, NY 14626 USA VITROS is a registered trademark of Ortho Clinical Diagnostics. © Ortho Clinical Diagnostics 2018-2019. Version 2.0 Pub. No. J65403_EN 29 of 29AH XSL Formatter V6.2 MR9 for Windows (x64) : 6.2.11.20953 (2015/05/28 17:24JST) Antenna House PDF Output Library 6.2.693 (Windows (x64))