Previous PageNext Page

Principle: | Clinical Significance: | Specimen: | Materials: | Reagents: | Standardization: | Procedure: | Limitations: | Results Derivation: | Expected Result(s) | Quality Control: | References:

Printer Friendly Version

Creatinine; i-STAT System

I. Principle:

The i-STAT System Creatinine is measured amperometrically. Creatinine is hydrolyzed to creatine in a reaction catalyzed by the enzyme creatinine amidohydrolase. Creatine is then hydrolyzed to sacrosine in a reaction catalyzed by the enzyme creatine amidinohydrolase. The oxidation of sarcosine, catalyzed by the enzyme sarcosine oxidase, produces hydrogen peroxide (H2O2). The liberated hydrogen peroxide is oxidized at the platinum electrode to produce a current, which is proportional to the sample creatinine concentration. Creatinine values assigned to i-STAT’s controls and calibration verification materials are traceable to the U.S. National Institute of Standards and Technology (NIST); Standard Reference Material SRM967. Select the Creatinine method traceable to IDMS Standard on the API survey.

II. Clinical Significance:

Elevated levels of creatinine are mainly associated with abnormal renal function and occur whenever there is a significant reduction in glomerular filtration rate or when urine elimination is obstructed. The concentration of creatinine is a better indicator of renal function than urea or uric acid because it is not affected by diet, exercise, or hormones. The creatinine level has been used in combination with BUN to differentiate between prerenal and renal causes of an elevated urea/BUN.

III. Specimen:

Lithium heparin whole blood venous sample is required. Fingerstick samples are not acceptable.

IV. Materials:

Dispo pipettes (CardinalHealth #P5201-3)

V. Reagents:

  1. i-STAT Creatinine cartridges - 25 cartridges/box (Abbott #03P84-25)
    1. Store stock cartridges at 2 - 8°C. Stable until expiration date on the box/cartridge.
    2. Cartridges must be at room temperature to be used for testing. The cartridges are stable for 2 weeks when stored at room temperature.
    3. Cartridges should be used immediately after opening pouch. If the pouch has been punctured, the cartridge should not be used.
    4. When cartridges are removed from the refrigerator the new 2 week expiration date must be written on each cartridge.
  2. i-STAT Level 1 Control (Abbott #06F12-01)
    1. Store control at 2 - 8°C. Stable until expiration date on the box.
    2. Allow the ampules to reach room temperature.
    3. Immediately before use, shake the ampule vigorously.
  3. i-STAT Level 3 Control (Abbott #06F14-01)
    1. Store control at 2 - 8°C. Stable until expiration date on the box.
    2. Allow the ampules to reach room temperature.
    3. Immediately before use, shake the ampule vigorously.
  4. i-STAT Calibration Verification Material (Abbott #06F1501)
    1. Store control at 2 - 8°C. Stable until expiration date on the box.
    2. Allow the ampules to reach room temperature.
    3. Immediately before use, shake the ampule.

VI. Standardization:

Cartridges are self-calibrating. Every cartridge includes a sealed foil pack, which contains a calibration solution with a known concentration. The concentration of Creatinine in the sample is calculated by comparing the sensors' response to the sample with that of the calibrant. A message and quality check code will be displayed if calibration fails.

VII. Procedure:

Refer to the “i-STAT; Operate” procedure.

VIII. Limitations:

  1. Ascorbate: 0.34 mmol/l ascorbate increases creatinine results by approximately 0.3 mg/dl.
  2. CO2:
    For creatinine values below 2 mg/dl:

    For PCO2 values above 40 mmHg, the values are increased by 6.9% for every 10 mmHg.
    For PCO2 values below 40 mmHg, the values are decreased by 6.9% for every 10 mmHg.
    [Cr]actual = [Cr]istat x {1 – (0.069 x [(PCO2 – 40)/10])}
    For creatinine values above 2 mg/dl:

    For PCO2 values above 40 mmHg, the values are decreased by 3.7% for every 10 mmHg.
    For PCO2 values below 40 mmHg, the values are increased by 3.7% for every 10 mmHg.
    [Cr]actual = [Cr]istat x {1 – (0.037 x [(40 - PCO2)/10])}
  3. The normal range of creatine concentration in plasma is 0.17 – 0.70 mg/dl (13-53 µmol/l) in males and 0.35 – 0.93 mg/dl (27-71 µmol/l) in females. Creatine may be elevated in patients using creatine supplements, experiencing muscle trauma or other primary or secondary myopathies, taking statins for hyperlipidemia control, or in patients with hyperthyroidism or a rare genetic defect of the creatine transporter protein.
  4. Hydroxyruea is a DNA synthesis inhibitor used in the treatment of various forms of cancer, sickle cell anemia and HIV infection. This drug is used to treat malignancies including melanoma, metastatic ovarian cancer and chronic myelogenous leukemia. It is also used in the treatment of polycythemia vera, thrombocytopenia and psoriasis. At typical doses ranging from 500 mg to 2 g/day, concentrations of hydroxyurea in patient’s blood may be sustained at approximately 100 to 500 µmol/L. Higher concentrations may be observed soon after dosing or at higher therapeutic doses.
  5. Acetaminophen has been shown to interfere at a concentration proscribed by the CLSI guideline, 1.32 mmol/L, which represents a toxic concentration, has been shown not to significantly interfere with i-STAT creatinine results.
  6. Acetylcysteine has been tested at two levels; the CLSI recommended level and a concentration of 0.30 mmol/L. The latter is 3 times the peak plasma therapeutic concentration associated with treatment to reverse acetaminophen poisoning. APOC has not identified a therapeutic condition that would lead to levels consistent with the CLSI recommended level. Acetylcysteine at a concentration of 10.2 mmol/L increased i-STAT creatinine results, while acetylcysteine at a concentration of 0.3 mmol/L did not significantly interfere with i-STAT creatinine results.
  7. Bromide has been tested at two levels; the CSLI recommended level and a therapeutic plasma concentration level of 2.5 mmol/L. The latter is the peak plasma concentration associated with halothane anesthesia, in which bromide is released. APOC has not identified a therapeutic condition that would lead to levels consistent with the CLSI recommended level. Bromide at a concentration of 37.5 mmol/L increased i-STAT creatinine results, while therapeutic range of bromide (2.5 mmol/L) did not significantly interfere with i-STAT creatinine results.

IX. Results Derivation:

  1. Creatinine results are displayed, and printed in mg/dl.
  2. Analytical Range: 0.20 - 20.0 mg/dl.
    Samples <0.2 mg/dl are reported as “
    <0.2 mg/dl”. Samples above the analytical range are reported as “>20.0 mg/dl”.
  3. Cartridge results flagged with *** indicates rejection of internal QC criteria. If this occurs, analyze the specimen again using another cartridge.
  4. A Quality Check message will occur if the analyzer detects a problem with the sample, sensors, mechanical or electrical functions of the analyzer during the test cycle. Refer to the i-STAT or i-Stat1 Troubleshooting guide for corrective action.

X. Expected Result(s) and/or Critical Values:

0.4 - 1.4 mg/dl

XI. Quality Control:

Note: The Creatinine I-STAT test cartridge was granted waived status 11/08. The control requirements listed in the procedure will continue to be used.

  1. Endogenous Control:
    The i-STAT System internal controls monitor the entire analytical process. The i-STAT System continuously monitors its electronic and mechanical components, thermal control subsystem, pressure transducers, battery voltage, temperature, and the flow of calibrant solution and sample within the cartridge. The performance of individual sensors and the integrity of the calibrant fluid is verified by comparing signals produced by the sensors in the calibrant fluid against factory established, statistically based expectation values. If at any point during the testing cycle a problem is detected, the analyzer stops, resets, and displays a message describing the problem and the next step to be taken.
  2. Exogenous Controls:
    1. Equivalent QC (EQC):
      The internal QC for this test monitors the complete analytic process; it is first level EQC. Therefore, the i-STAT Level 1 and Level 3 Controls are routinely run once per month. Since the Electronic Simulator is performed on each i-STAT System each day of use and the Internal Cartridge Controls monitor the entire analytic process, the monthly EQC will be performed on a representative i-STAT unit at each site. Baseline EQC testing will be performed on a representative i-STAT unit within the UCL system and will be scanned into the record.
    2. The i-STAT Level 1 and Level 3 Controls are also run for each lot number of each shipment received regardless of whether the lot number has changed.
    3. This EQC level 1 testing system is low volume. It doesn’t generate enough external control data to derive operational control parameters in house on a per lot basis. (In the first five months of operation only eight trials per level were acquired.) Limited retrospective experience indicates that the G3+, Crea cartridge i-STAT Creatinine testing system will reliably recover something very close to the manufacturer’s package insert mean at both levels but the posted ranges are generous with respect to the system’s typical performance, early problem detection and the clinical application. We will use the manufacturer’s Value Assignment Sheets means, specific for the i-STAT CLEW software version, control lot number and the cartridge lot number, with the following acceptable ranges for the external controls:
      L1: X +/- 0.5 mg/dl
      L3: X +/- 0.2 mg/dl
      If control results are within these acceptable ranges, the cartridges can be used. Record results on the i-STAT System QC log. Record on each box of controls that was received in the shipment, that QC was OK.
    4. If control results are not acceptable, repeat them once. If control results are still not acceptable, notify Supervisor and the Office of the Technical Director so replacement cartridges can be obtained.
    5. The Control Value Assignment Sheets will be distributed following i-STAT software upgrades; they can also be obtained at www.i-stat.com/products/valsheets.
  3. Electronic Simulator:
    The Electronic Simulator will be run each shift of use. The Electronic Simulator provides an independent check on the ability of the analyzer to take accurate and sensitive measurements of voltage, current and resistance from the cartridge. An analyzer will pass or fail this electronic test depending on whether or not it measures these signals within limits specified in the analyzer software. Refer to the
    i-STAT Operate procedure for instructions on performing the Electronic Simulator Test.
  4. The criteria for accepting or rejecting a patient run is stated in the “Quality Control, General” protocol in the Quality Assurance manual.
  5. On receipt of new cartridges, verify that the transit temperatures were satisfactory using the four-window temperature indicator strip included with the cartridge boxes.
  6. Analytical Range:
    0.20 - 20 mg/dl
  7. Calibrator:
    Calibrator solution is included in the test cartridge.
  8. Calibration Frequency:
    Every cartridge is calibrated with calibration solution of known concentration that is contained in the cartridge.
  9. Calibration Verification:
    Calibration verification is performed every 6 months using the i-STAT Calibration Verification material. Since the Electronic Simulator is performed on each i-STAT each shift of use and the Internal Cartridge Controls monitor the entire analytic process, Calibration Verification will be performed on a representative i-STAT unit at each site.

    Note: i-Stat’s position is that it is the cartridges, or more specifically, the sensors, rather than the analyzers that are subject to the six-month check on the accuracy of the reportable range. This supports the i-Stat claim that all analyzers that pass the Electronic Simulator test are equivalent, which should preclude the testing of three levels, twice a year, on each and every analyzer on site.
  10. Control Ranges:
    Acceptable control ranges are obtained from the manufacturer’s control value assignment sheets.

XII. References:

  1. i-Stat Creatinine Test Information Sheet. Abbott Point of Care. East Windsor, NJ. 1/25/05
  2. i-Stat Control package insert. Abbott Point of Care. East Windsor, NJ. 9/15/06
  3. i-Stat Calibration Verification Control set package insert. Abbott Point of Care. East Windsor, NJ.
  4. i-STAT Creatinine Information Sheet. Abbott Point of Care. East Windsor, NJ. Art: 714183-00M 9-2-08.
  5. i-Stat Technical Bulletin: Packaging Updates. Abbott Point of Care. Abbott Park, IL. June 15, 2010.
  6. i-STAT Creatinine Information Sheet. Abbott Point of Care. Abbott Park, IL. Art. 71418300R 9/17/2010.

 

  1. April 2008 L. McGovern
  2. October 2008 S. Raymond (Revised: X.2.C.)
  3. November 2008 L. McGovern (Revised: I.; X.2.C.; XI.4.; X.2.E.)
  4. February 2009 L. McGovern (Revised: X.Note, added)
  5. December 2010 L. McGovern (Revised: VII.; XI.6.)

 

Comprehensive Review:

Pathologist:

Technical Director:

 

Interim Review:
July 2010 L. McGovern (Revised: III.1.; XII.5.)
July 2011 B. Speetzen (no changes)


Printer Friendly Version