Frequently Asked Questions

1. When can I start using the new IDMS-Traceable MDRD Study equation?
   
   
2. How can IVD manufacturers obtain the SRM 967 from NIST?
   
   
3. What is the status of the commutability study being performed with SRM 967?
   
   
4. What should IVD manufacturers be doing at this time?
   
   
5. What should clinical laboratories be doing at this time?
   
   
6. What should software vendors be doing at this time?
   
   
7. What are the PT/EQA implications of the Creatinine Standardization Program? Will my lab fail a PT/EQA challenge as a result of recalibration?
   
   
8. The NKDEP recommends reporting serum creatinine values in mg/dL to two decimal places (e.g., 0.95 mg/dL). Is there any commercially available clinical technology that provides serum creatinine results with an accuracy of 0.01 mg/dL?
   
   
9. What is the FDA's stance on the Creatinine Standardization Program? If recalibration of routine methods will result in changes to serum creatinine reference intervals, will IVD manufacturers need to file 510ks for their methods?
   
   
10. What if providers ask about the applicability of the MDRD Study equation in patients who are aged 70 or older?
    
    
11. My lab is now using the Roche creatinine assay, which has already been calibrated to be traceable to IDMS reference materials. Should we be using the original conventional calibration MDRD equation for estimating GFR or using some type of correction factor?
    
    
12. NKDEP recommends reporting estimated GFR (eGFR) values greater than or equal to 60 mL/min/1.73 m² as "≥60 mL/min/1.73 m²" and not as an exact number. What is the basis for the recommendation, and would it be erroneous to continue to report the actual value above 60?
    
    

1. When can I start using the new IDMS-Traceable MDRD Study Equation?

Labs can begin using the IDMS-Traceable MDRD Study equation as soon as they begin to use a creatinine method that has been calibrated to be traceable to IDMS. Please note that the IDMS-Traceable MDRD Study equation should be used only with those creatinine methods that have been recalibrated to be traceable to IDMS. The original MDRD Study equation should be used with all other methods. Please see Suggestions for Laboratories for more information about the two equations. If you have any questions about the traceability of the calibration for the creatinine method in use in your laboratory, NKDEP recommends that you contact the reagent and/or calibrator manufacturer for assistance.

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2. How can IVD manufacturers obtain the SRM 967 from NIST?

The NKDEP will post this information when NIST announces the release of SRM 967.

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3. What is the status of the commutability study being performed with SRM 967?

The commutability study has been carried out. Both SRM 967 and CAP LN24 samples appear to be commutable with virtually all methods using EP14-A2's +/- 95% PI criteria. For more information on the commutability study results, please see the Eckfeldt presentation from the July 27, 2006 NKDEP Manufacturers' Forum. Please subscribe to free email updates from the NKDEP so that we can keep you apprised of NIST's release of SRM 967.

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4. What should IVD manufacturers be doing at this time?

Please let your customers know that you will be participating in the NKDEP Creatinine Standardization Program, and inform them of your anticipated timeline for this process. At least one IVD reagent and systems manufacturer has already recalibrated one or more of their creatinine methods to be traceable to IDMS, but, for most manufacturers, it is anticipated the standardization program will begin in 2006 and will require 1-2 years to be fully implemented in all routine clinical laboratories. The NKDEP has developed a letter that you can forward to your customers to help explain the rationale behind the recalibration program and the importance of participation by all stakeholders, including manufacturers, laboratories, clinicians, and proficiency testing providers. More specific recommendations for IVD manufacturers are posted on the NKDEP Recommendations section of this website.

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5. What should clinical laboratories be doing at this time?

Please begin reporting estimated GFR using the appropriate MDRD equation as described in detail on the Suggestions for Laboratories page. Please work with IVD manufacturers and software vendors to discuss and coordinate plans for recalibration so that you can begin using the IDMS-Traceable MDRD Study equation immediately upon availability of an IDMS-traceable method. Please see Suggestions for Laboratories for more detailed information for laboratories, review specific recommendations for clinical laboratories that are now posted on the NKDEP Recommendations section of this website, and subscribe to free email updates from the NKDEP so that we can keep you informed of new developments. Laboratory directors also should refer to the Clinical Laboratory News article, "NKDEP Launches Creatinine Standardization Program: Why Labs Should Recalibrate Serum Creatinine Methods, Report Estimated GFRs" (PDF, 489K).

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6. What should software vendors be doing at this time?

The NKDEP encourages you to provide your customers with the option to use either the original MDRD Study equation or the IDMS-Traceable MDRD Study equation—depending on which equation is appropriate for the creatinine method in use. Because there are legacy recommendations for drug dose adjustments based on other renal function assessment tools such as the Cockcroft-Gault (C-G) equation for estimating creatinine clearance, we recommend that you also offer an option to adjust the creatinine value used in the C-G equation to account for differences between IDMS-traceable creatinine results, compared to results reported with a legacy creatinine method calibration. Although the creatinine method manufacturer should provide the calibration adjustment parameters for each creatinine method, the software should offer the flexibility, at a minimum, to accept both constant and proportional adjustment parameters. In some instances, polynomial data transformations may be required. More specific recommendations for software vendors are posted on the NKDEP Recommendations section of this website. Please subscribe to free email updates from the NKDEP so that we can keep you informed of new developments.

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7. What are the PT/EQA implications of the Creatinine Standardization Program? Will my lab fail a PT/EQA challenge as a result of recalibration?

NKDEP is collaborating with PT/EQA providers and IVD manufacturers to recommend appropriate grading during the recalibration process (which is expected to occur during 2006-2007) so that laboratories do not fail a PT/EQA challenge as a result of creatinine method recalibrations undertaken by the IVD method/systems manufacturers. It is anticipated that bimodal distributions of results may be observed due to the simultaneous availability of two different calibration schemes in the population of customer laboratories during the transition. PT/EQA providers are asked to create new instrument/method peer groups that reflect the calibration status (conventional or IDMS-traceable) of serum and urine creatinine methods in use by participant laboratories. Participating laboratories will need to choose the correct instrument/method peer group for the creatinine calibration currently used by their laboratory. More specific recommendations for PT/EQA providers are posted on the NKDEP Recommendations section of this website. Please subscribe to free email updates from the NKDEP so that we can keep you apprised of how PT/EQA providers will be managing this process.

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8. The NKDEP recommends reporting serum creatinine values in mg/dL to two decimal places (e.g., 0.95 mg/dL). Is there any commercially available clinical technology that provides serum creatinine results with an accuracy of 0.01 mg/dL?

Most commercially available creatinine methods allow the user to select two decimals for reporting. This does not substantively affect the accuracy of the measurement, but it does reduce the imprecision introduced when rounding the result to a single decimal. This imprecision reduction is reflected as less imprecision in the estimated GFR using the MDRD Study equation, especially for creatinine values that correspond to eGFR near the 60 mL/min/1.73 m² threshold. Regarding the software for your system, there is likely a configuration setting that needs to be activated or modified to enable reporting results to two decimal places. Ask your equipment vendor and software vendor how to report to two decimal places.

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9. What is the FDA's stance on the Creatinine Standardization Program? If recalibration of routine methods will result in changes to serum creatinine reference intervals, will IVD manufacturers need to file 510ks for their methods?

IVD manufacturers should refer to "Deciding When to Submit a 510(k) for a Change to an Existing Device," found on the Internet at www.fda.gov/cdrh/ode/510kmod.pdf.

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10. What if providers ask about the applicability of the MDRD Study equation in patients who are aged 70 or older?

Chronic kidney disease is often missed among older patients due to expected age-related reduction in creatinine production. The NKDEP recommends reporting the estimated GFR (eGFR) value for individuals over age 70 because eGFR is a diagnostic tool and, while it has not been validated specifically in older adults, there is no strong evidence to doubt that it is a clinically appropriate tool.

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11. My lab is now using the Roche creatinine assay, which has already been calibrated to be traceable to IDMS reference materials. Should we be using the original MDRD Study equation for estimating GFR or using some type of correction factor?

Customers using Roche Creatinine methods should use the IDMS-Traceable MDRD Study equation.

• Roche Enzymatic Creatinine method is traceable to IDMS.
• Roche Global Creatinine Jaffe methods are traceable to IDMS.
• Roche US Creatinine Jaffe methods are directly traceable to SRM 914a and indirectly traceable to IDMS through a Masterlot.

Please see Suggestions for Laboratories for more information about which MDRD Study equation to use under which circumstances, and review specific recommendations for clinical laboratories posted on the NKDEP Recommendations.

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12. NKDEP recommends reporting estimated GFR (eGFR) values greater than or equal to 60 mL/min/1.73 m² as "≥60 mL/min/1.73 m²" and not as an exact number. What is the basis for the recommendation, and would it be erroneous to continue to report the actual value above 60?

There are several reasons to not report values above 60: 1) creatinine method standardization is not complete and there is variability among methods that has a greater impact at lower creatinine (which equates to a higher eGFR); 2) some creatinine methods have excessive imprecision that also has a greater influence on variability of results at lower creatinine/higher eGFR; and 3) the MDRD equation itself has greater variability at lower creatinine/higher eGFR. For these reasons and others, it would be erroneous to continue to report numeric values above 60. For more information, please refer to the "Estimating GFR" section of Suggestions for Laboratories and the NKDEP Laboratory Working Group report in Clinical Chemistry.