Today, in the United States alone, there are 10 to 20 million people with chronic kidney disease, or CKD. Most cases of CKD exist for many years before progressing to end-stage renal disease (ESRD), a complete or near-complete failure of the kidneys.

Currently the most common cause of ESRD—type 2 diabetes—has been growing at a troubling rate, particularly among young adults. It's no wonder that public health officials urgently want to raise awareness of the seriousness of kidney disease and push for early detection and intervention.

Enter the National Kidney Disease Education Program (NKDEP)—an initiative of the National Institutes of Health—and the recent release of a major report by their Laboratory Working Group. The report, published in Clinical Chemistry's January 2006 issue, contains new recommendations for measuring serum creatinine and for reporting estimated glomerular filtration rate (GFR), two key indices of kidney function. The NKDEP's Creatinine Standardization Program is intended to reduce bias in the measurement of serum creatinine to yield more accurate estimates of GFR, thus delivering meaningful results to people in need.

The Recommendations

The NKDEP Laboratory Working Group was created to review and address the problems related to serum creatinine measurement for estimating GFR and to prepare recommendations to standardize and improve creatinine measurement. The group focused on the problem of calibration bias between laboratories that created the variability in estimated GFR. After studying the issues, it was decided that there was a need for a global standardization program that would involve a coordinated effort between IVD manufacturers, clinical laboratories, pharmacists, regulatory organizations and LIS vendors. In their January report, the Laboratory Working Group made two main recommendations:

• Laboratories should automatically report estimated GFR when serum creatinine is ordered.
• Laboratories should use the standard MDRD equation (derived from the Modification of Diet and Renal Disease study) when estimating GFR.

Automatically reporting estimated GFR is a practical way to identify people with kidney disease who might go untreated otherwise. If detected early, kidney disease can be slowed and in some cases even halted—which makes the accurate estimation of kidney function critical to patients and physicians. The NKDEP also suggests that labs use the standard MDRD equation to estimate GFR from serum creatinine, as it is highly reliable when the patient's age, sex and race are known.

Using the Standard MDRD Equation

The report also emphasized the fact that laboratorians must remember there are two different MDRD equations: the conventional calibration MDRD equation and the MDRD equation traceable to isotope dilution mass spectrometry (IDMS). The conventional calibration MDRD equation should be used only by labs currently using creatinine methods that have not been calibrated to be traceable to IDMS reference measurement procedures, while the IDMS-traceable MDRD equation should be used with creatinine methods that have been calibrated to be traceable to IDMS. Due to the complexity of implementing these equations, the NKDEP strongly recommends that laboratories work with their LIS vendors to apply the GFR calculations on their LIS systems.

Of the several methods currently available for creatinine measurements (Jaffe rate, enzymatic, etc.), the NKDEP considers the IDMS-traceable method to be the method of choice for establishing the true concentration of creatinine in serum because of its excellent specificity. All labs should eventually introduce serum creatinine methods that are calibrated to be IDMS-traceable so that there will be a uniform calibration standard within the clinical lab community.

The Next Step

The NKDEP's Creatinine Standardization Program will begin in earnest once the National Institute of Standards and Technology (NIST) releases a new serum creatinine reference material. The release of the material, expected around mid-2006, will mark the official start of the restandardization process for IVD manufacturers. Once material is made available, it will be several months until manufacturers can complete the restandardization process. This will lead to similar creatinine values across the various methods now available from different manufacturers.

In the coming months, the bulk of these restandardization efforts will fall on the IVD industry. IVD manufacturers will then provide information to clinical laboratories on the relationship between the restandardized method and the previous conventional calibration method. For Beckman Coulter, commitment to the Creatinine Standardization Program is a priority and we will continue to partner with clinical laboratories as this important scientific effort moves forward. As developments continue to occur, look for more information and program updates in future issues of Diagnostics Today Online.

Suggestions for Laboratories: What You Need to Know

The NKDEP encourages clinical laboratories to communicate with healthcare providers—including pharmacists—about the clinical issues associated with restandardizing serum creatinine measurement to be traceable to IDMS.

Be prepared to implement the following:

• Labs should contact their LIS vendor for information on how to set up the calculation for the MDRD equation for GFR estimation.
• Creatinine results should be reported to two decimal places when mg/dL units are used and nearest whole number when values are reported in µmol/L. This reduces the contribution of rounding-up errors and improves the precision of the result.
• Labs should notify the pharmacy and physicians that the serum creatinine reference interval will change after the restandardization. The effect on measured creatinine clearance will vary depending on the procedure used to calibrate serum measurements.
• For most patients, an estimated GFR using the MDRD equation is more accurate than a creatinine clearance calculated from serum and urine measurements.
• Following implementation by IVD manufacturers of restandardization (traceable to IDMS) for serum creatinine methods, other creatinine clearance and/or GFR estimating equations such as Cockcroft-Gault, Schwartz or Counahan-Barratt will give values that will be different in most cases.