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Creatinine
Standardization Recommendations
In vitro diagnostic (IVD)
manufacturers are crucial partners in the successful implementation of
the Creatinine Standardization Program. For IVD manufacturers, the
following steps are necessary:
- Continue using or recommending the
Original Modification of Diet in Renal Disease (MDRD) Study equation
for routine methods that have not
been calibrated to be traceable to IDMS.
- Calibrate serum creatinine
methods to be traceable to an isotope dilution mass spectrometry (IDMS)
reference measurement procedure. Standardization of method calibration
will reduce the interlaboratory bias in results and yield more accurate
estimated GFR (eGFR) when using the IDMS-traceable MDRD Study
equation.
- A new reference material with
IDMS-traceable creatinine values (NIST SRM 967) is now available
for calibrating routine methods (see information on SRM 967).
- Alternatively, routine methods
can be calibrated with the assistance of an existing IDMS reference
measurement laboratory. The Joint Committee for Traceability in
Laboratory Medicine (JCTLM) lists approved reference measurement
procedures and the submitting laboratories at www.bipm.fr/utils/en/xls/jctlm_listI.xls.
JCTLM also provides a list of laboratories that can provide reference
measurement services.
- Coordinate with customer
laboratories so that, upon using a method with IDMS-traceable
calibration, they immediately begin using the IDMS-traceable MDRD Study
equation. During the transition to IDMS-traceable calibration, methods
that produce results that have acceptable bias [as defined in Clinical
Chemistry 2006;52(1):5-18] when compared to an IDMS-traceable
method should use the IDMS-traceable MDRD Study equation.
- Communicate to customers the
clinical issues associated with introducing a serum creatinine method
that is calibrated to be traceable to IDMS. IVD manufacturers should:
- Provide a serum creatinine
reference interval appropriate for the method.
- The effect on measured
creatinine clearance will vary depending on the procedure used to
calibrate serum and urine measurements. Creatinine clearance values
based on measured serum and urine creatinine results may increase and a
new reference interval and interpretive criteria may need to be
established. Read NKDEP’s recommendations for clinical
laboratories for more information on using
creatinine clearance to assess kidney function.
- Describe the relationship between
creatinine results when measured by methods that have IDMS-traceable
calibration compared to the results obtained using methods with
traditional calibration. Include detailed descriptions (including
mathematical conversion factors, equations, or functions) of the impact
of a calibration change for both serum and urine creatinine values,
with emphasis on the 0.5 to 2.5 mg/dL (45 to 220 µmol/L)
range of interest. This information will ensure that customers or
laboratories using any of the pharmacy drug-dosing approaches can
adjust IDMS-traceable creatinine values for use with appropriate legacy
dosing reference tables and algorithms (such as serum creatinine value;
GFR or creatinine clearance based on estimating equations other than
the MDRD Study equation; or traditionally measured creatinine clearance
from serum and urine values). Read NKDEP’s
recommendations for clinical laboratories and for pharmacists and
authorized drug prescribers for more information on implications for
drug dosing.
- Communicate that equations, other
than the IDMS-traceable MDRD Study equation, used to estimate kidney
function, such as Cockcroft-Gault, Schwartz, or Counahan-Barratt, will
give values that, in most cases, are higher than the values obtained
using traditionally calibrated creatinine methods. This change in
calibration will affect interpretive criteria based on these estimates
of kidney function.
- Emphasize that creatinine
measurements at the low values usually observed in pediatric patients
have greater measurement variability than for values seen in adults.
Estimates of kidney function based on these values also will have
greater variability than for adults.
- Improve the precision of creatinine
methods to meet the total error goal for serum creatinine measurement
described in Figure 3 in the paper published in Clinical
Chemistry 2006;52(1):5-18 (reproduced below).
This figure provides an error budget for creatinine measurement in the
range 1.00-1.50 mg/dL (88.4-133 µmol/L) that will ensure less
than 10 percent increase in the relative error of the eGFR. An example
of method performance, in the absence of any interfering substances in
the serum sample, that would achieve this total error goal is
analytical imprecision (including interlaboratory calibration
variability) SD <0.08 mg/dL (7.1 µmol/L) and
analytical bias (compared to an IDMS reference measurement procedure)
<0.05 mg/dL (4.4 µmol/L) at a serum creatinine
concentration of 1.00 mg/dL (88.4 µmol/L).
- Ensure optimal
method performance at 1.00 mg/dL (88.4 µmol/L) for existing
and new methods, and ensure that comparable trueness and imprecision
extend throughout the analytical measurement range. Method imprecision
at concentrations <1.00 mg/dL (88.4 µmol/L) should be
addressed to reduce the uncertainty in eGFR for pediatric populations,
and possibly to allow extension of eGFR to values ≥60
mL/min/1.73 m2.
- Design instruments that report
serum creatinine values as mg/dL to two decimal places, or as
µmol/L to the nearest whole number. This will reduce the
contribution of a rounding error when using the MDRD Study equation.
- Address analytical nonspecificity issues
in routine serum creatinine methods. The NKDEP Laboratory Working Group
is currently developing recommendations for creatinine method
specificity requirements.
- Communicate with Proficiency
Testing and External Quality Assessment Scheme (PT/EQA) providers to
inform them when a revised creatinine calibration will become
effective, and work with the PT/EQA provider to develop appropriate
instrument/method peer groups for participants to be evaluated
appropriately. Read NKDEP’s recommendations for PT/EQA providers.
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