Estimating GFR

Xchange newsletter - Spring 2007

Early detection of CKD

Chronic kidney disease (CKD) affects around 10% of the population and is often asymptomatic until renal function is already severely reduced. Treatment can prevent, or at least delay, progression of CKD and the need for renal replacement therapy. Consequently, identification of those at risk from, or in the early stages of, CKD is vital.

In April 2006, the Department of Health recommended the most sensitive way to detect kidney disease was by use of a formula-based estimation of glomerular filtration rate. To ensure a consistent approach to reporting eGFR and to reduce inter-laboratory variation, an advisory group was established. Here we take a closer look at eGFR.

Back to basics

Serum creatinine is a simple test and a commonly used indicator of renal function. Creatinine is produced by muscles at a fairly constant rate. It is almost completely excreted by the kidneys and therefore can be used as a measure of how well they are working.

However, serum creatinine is not suitable for detecting early-stage kidney disease. In addition, levels are proportional to muscle mass and so vary depending on age and gender.

GFR

Glomerular filtration rate (GFR) is an alternative test of kidney function. It is defined as the volume of fluid filtered from the renal glomerular capillaries in a given period. Gold standard methods of assessing GFR are technically demanding, expensive, time consuming and unsuitable for widespread identification of CKD in the ‘at risk’ population.

Serum creatinine levels, combined with an algorithm that corrects for some of the more significant non-renal influences, provide an estimated GFR (eGFR). This approach improves sensitivity.

Standardisation

Lack of standardisation between creatinine assays has been shown to create errors of +/- 9-18 µmol/L, which equates to a 10-20% error of normal serum creatinine (88 µmol/L). In 2003, the College of American Pathologists distributed an educational sample with a certified creatinine concentration of 80 µmol/L. The average bias across methodologies was a positive 11 µmol/L (the Abbott bias observed was 9 µmol/L).

Despite these inter-laboratory variations, reporting eGFR still enables identification of CKD in patients who would be missed using serum creatinine alone.

The National Kidney Disease Education Program (NKDEP) encourages laboratories to automatically report eGFR when serum creatinine is ordered and has launched the Creatinine Standardisation Program using a National Institute of Standards and Technology (NIST) fresh frozen primary serum assigned by GC/LC-IDMS.

UK NEQAS

In the UK, the Department of Health rolled out eGFR from April 2006. UK NEQAS was part of the advisory group and probed the robustness and accuracy of creatinine measurements to ensure good, meaningful information on measuring and standardisation.

Data from an initial pilot were used to harmonise eGFR results by offering laboratories parameters to include in their eGFR algorithms.

Finlay Mackenzie, deputy director Wolfson EQA Laboratory, recommends that, "Method-specific slope adjustors should be used by laboratories in their calculation of eGFRs. This should express the eGFR in the same ‘currency’ as if those eGFRs had been derived from an IDMS traceable method. To date, we are satisfied with the response to the EQA scheme and ongoing monitoring will be implemented to ensure the slopes and intercepts remain valid."

For further information on the importance of eGFR visit the following websites.

• National Kidney Disease Education Program <www.nkdep.nih.gov>
• United Kingdom National External Quality Assessment Service <www.ukneqas.org.uk>
• Lab Tests Online UK <www.labtestsonline.org.uk>

New solutions coming soon!

Abbott has three assays currently in development. Both creatinine assays are planned to be traceable to the new standard.

1. Creatinine Next Generation Assay (A Jaffe Kinetic method - available soon)
2. Creatinine Enzymatic Assay (available in 2007)
3. Cystatin C (currently in development) – Cystatin C may serve as an alternative to creatinine for monitoring kidney function. Cystatin C has better diagnostic sensitivity so it may be especially useful in detecting early decreases in kidney function