IDMS-traceable creatinine

IDMS-traceable creatinine - Creat (IDMS)

IMPORTANT - Q and A

1) Does the current software program utilize the newer creat-IDMS value with the lower reference range of (0.66 – 1.25) or the traditional serum creatinine value with the reference range of (0.8- 1.5)?

The current Multi-CRCL program does NOT utilize the CREAT-IDMS value.   If the user selects 'Creatinine values reported as CREAT(IDMS)' under "Select serum creatinine reference standard" The CREAT-IDMS is converted into an approximate standard (conventional, old) creatinine value so that the calculated creatinine clearance values are in-line with the commonly reported values in package inserts, drug dosing guides and other references.

        [ Non-IDMS CREATININE (mg/dL) = creat-IDMS (mg/dL) x 1.065 + 0.067   ]
                Contact your local laboratory director. Alternatively , review these sample links: [1 ] [2 ]

2) What does IDMS stand for?
Isotope dilution mass spectrometry (IDMS) reference measurement procedure.

There are several reasons (and implications) why this new standardized value (creat-IDMS) is being reported by labs throughout the world, and the conventional value is being eliminated.....

Here are some direct quotes from a valuable reference site:
http://www.nkdep.nih.gov

1.Following implementation of revised calibration for serum creatinine methods, use of the IDMS-traceable Modification of Diet in Renal Disease (MDRD) Study equation will give a more accurate value for eGFR in adults. [Dave: wondering why? See "Serum creatinine assay errors" below.

2.The serum creatinine reference interval will change, in most cases, to lower values. The magnitude of change is likely to be between 5 to 20 percent.
[Dave: The greater accuracy of the IDMS value produces slightly lower creatinine values. When these lower values are used in conventional equations such as the Cockcroft and Gault equation, higher than expected results (clearances) are expected. ]

3.Creatinine clearance values based on measured serum and urine creatinine results may change. A new reference interval and interpretive criteria may need to be established for creatinine clearance.

4.Following implementation of revised calibration for serum creatinine methods, creatinine clearance estimating equations such as Cockcroft-Gault, Schwartz, or Counahan-Barratt will, in most cases, give values that are higher than those values obtained before creatinine method recalibration.

Pharmaceutical manufacturers have used the Cockcroft-Gault equation to estimate kidney
function, but there is no version of this equation available for use with an IDMS-traceable creatinine value.

Serum Creatinine Assay Errors and Revision
Since serum creatinine is the variable with the greatest impact in GFR prediction equations, the need for reliable serum creatinine measurements is of utmost importance. Commonly used creatinine assay methodologies include (1) alkaline picrate methods (e.g., Jaffe method [classic] and compensated [modified] Jaffe methods [used in MDRD study], (2) enzymatic methods, (3) high-performance liquid chromatography, (4) isotope dilution mass spectrometry (IDMS), (5) gas chromatography, and (6) liquid chromatography. Many factors may produce inherent errors in these assay methodologies, including patient-specific variables (diseases, dietary factors, pregnancy, hydration status, serum glucose values, blood pressure), variations in GFR measurements (measurement of serum and urine filtration markers, urine flow-rate assessment and collection), and errors in creatinine measurements due to the presence of interfering substances and assay methodology inaccuracies.

With the commonly used classic and modified Jaffe methods, up to 20% of the color reaction may be due to the presence of noncreatinine chromagens in the serum sample, thereby overestimating serum creatinine and therefore underestimating CLcr. This error is most significant within the normal reference range of serum creatinine values.

Other commonly used assays, such as the kinetic alkaline picrate assay, also report a serum creatinine value higher than actual (positive bias), thereby underestimating CLcr most significantly within the upper range of normal for creatinine values—values that define early-onset CKD.[16] A study of the effects of the Jaffe alkaline picrate assay procedure found that this method overestimates MDRD-calculated GFRs by approximately 50% in patients with a serum creatinine of 1.75 mg/dL.[17]

An NKDEP laboratory working group, formed for the purpose of reevaluating serum creatinine assay performance worldwide, determined that various serum creatinine assays are suboptimal for use as a universal predictor of a patient's actual serum creatinine value[16,18-22] and recommended reporting calculated GFR values over 60 mL/min/1.73 m2 as simply >60 mL/min/1.73 m2 when older serum creatinine assays are used. The NKDEP working group concluded that the lack of calibration standardization traceable to a single accurate standard results in differing degrees of accuracy with serum creatinine assay methods used by various assay kit manufacturers. The group further concluded that all current equations for estimating GFRs, including the MDRD equations and the Cockcroft–Gault equation, are less accurate in patients with normal and slightly increased serum creatinine. [23] This led the group to prepare recommendations to standardize and improve creatinine measurement.[24]

The NKDEP's Creatinine Standardization Program, in conjunction with the Food and Drug Administration, is encouraging all manufacturers of creatinine assay kits to recalibrate routine serum creatinine methods to be traceable to an IDMS standard and to work with clinical laboratories to coordinate the release of this recalibrated assay with the introduction of a revision of the MDRD4 equation to estimate the GFR appropriate for use with these new assay standards. This new equation (MDRD4revised), in conjunction with the IDMS-traceable assay, allows GFR estimates to be reported up to 90 mL/min/1.73 m2; that is, only values over 90 should be reported as >90 mL/min/1.73 m2. The NKDEP working group also developed a website for health care professionals to provide and explain their creatinine standardization program recommendations and has added recommendations specifically for pharmacists for drug dosing.

Although the working group currently recommends the use of the revised four-variable MDRD equation for laboratories also using the IDMS-traceable creatinine assay, it also recommends the use of the original four-variable MDRD equation in the interim until all clinical laboratories can begin using the newer IDMS-traceable serum creatinine assay.

http://www.nkdep.nih.gov/labprofessionals/Pharmacists_and_Authorized_Drug_Prescribers.htm

Original MDRD Study Equation
Conventional units
GFR (mL/min/1.73 m²) = 186 x (S_cr)^-1.154 x (Age)^-0.203 x (0.742 if female) x (1.212 if African-American)

SI units
GFR (mL/min/1.73 m²) = 186 x (S_cr/88.4)^-1.154 x (Age)^-0.203 x (0.742 if female) x (1.212 if African-American)

NOTE: This equation should be used only with those creatinine methods that have not been calibrated to be traceable to IDMS.

IDMS-traceable MDRD Study Equation
Conventional units
GFR (mL/min/1.73 m²) = 175 x (S_cr)^-1.154 x (Age)^-0.203 x (0.742 if female) x (1.212 if African American)

SI units
GFR (mL/min/1.73 m²) = 175 x (S_cr/88.4)^-1.154 x (Age)^-0.203 x (0.742 if female) x (1.212 if African American)

NOTE: This equation should be used only with those creatinine methods that have been calibrated to be traceable to IDMS. If you do not know whether your laboratory uses a method that has been calibrated to be traceable to IDMS, talk to your in vitro diagnostics manufacturer representative.

References

1) Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16(1):31-41

2) Davis GA, Chandler MH. Comparison of creatinine clearance estimation methods in patients with trauma. Am J Health-Syst Pharm 1996;53:1028-32.

3) Dawson-Saunders B, Trapp RG. Basic and Clinical Biostatistics. 2nd ed. Norwalk, CT: Appleton & Lange; 1994.

4) Dettli LC. Drug dosage in patients with renal disease. Clin Pharmacol Ther 1974;16:274-80.

5) Drusano LG, Munice HL, Hoopes JM et al. Commonly used methods of estimating creatinine clearance are inadequate for elderly debilitated nursing home patients. J Am Geriatrics Soc 1998;36:437-41.

6) Hailemeskel B, Namanny M, Kurz A. Estimating aminoglycoside dosage requirements in patients with low serum creatinine concentrations. Am J Health-Syst Pharm 1997;54:986-7.

7) Jelliffe RW. Estimation of creatinine clearance when urine cannot be collected. Lancet 1971;1:975-6.

8) Levey AS, Greene T, Kusek JW, et al. A simplified equation to predict glomerular filtration rate from serum creatinine (Abstr) J Am Soc Nephrol 2000;(11):155A

9) Levey AS, Greene T, Schluchter MD, et al. Glomerular filtration rate measurements in clinical trials. Modification of Diet in Renal Disease Study Group and the Diabetes Control and Complications Trial Research Group. J Am Soc Nephrol 1993;4(5):1159-71

10) Levey AS. Assessing the effectiveness of therapy to prevent the progression of renal disease. Am J Kidney Dis 1993;22(1):207-14

11) Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130(6):461-70

12) Rhodes RS, Sims PJ, Culbertson VL et al. Accuracy of creatinine clearance estimates in geriatric males with elevated serum creatinine clearance. J Geriatric Drug Ther 1991;5:31-45.

13) Smythe M, Hoffman J, Kizy K et al. Estimating creatinine clearance in elderly patients with low serum creatinine concentrations. Am J Hosp Pharm 1994;51:189-204.