Guidelines for laboratories: calculating estimated GFR for children
In view of the ongoing global creatinine standardization initiative, the older equations for estimating glomerular filtration rate (GFR) in children and infants will no longer be valid. Blood, serum, and plasma creatinine values will generally be lower for methods that have been calibrated to be traceable to an isotope dilution mass spectroscopy (IDMS) reference-measurement procedure.
Below you fill find information on the following topics as they relate to estimating GFR for children:
Potential problems following recalibration to be traceable to IDMS
It is expected that the in vitro diagnostics (IVD) industry will complete the recalibration of routine blood, serum, or plasma creatinine methods during 2009. There are two principal measurement issues that affect estimated GFR differently in children than in adults.
- The generally lower serum creatinine concentration in children makes the influence of a measurement error proportionally larger than the same magnitude error in an adult sample.
- The generally lower serum total protein, particularly in very young children, can alter the relative magnitude of the influence of the nonspecific reaction of proteins in alkaline picrate (“Jaffe”) methods.
Enzymatic creatinine methods
For enzymatic creatinine methods, which are not influenced by total protein concentrations, modification of the coefficients in the Schwartz equation can be performed to permit a modified Schwartz equation to be used with blood, serum, or plasma creatinine methods that have calibration traceable to IDMS. Research to support a revised children’s equation has been accepted for publication (Schwartz GJ, et al. Formulas to estimate GFR in children with chronic kidney disease. J Am Soc Nephrol. 2008, in press). The new equations were based on an enzymatic creatinine method that had calibration traceable to an IDMS reference measurement procedure. One of the new equations was based on serum creatinine, height, and age and is referred as the interim Schwartz equation. The interim Schwartz equation is intended only for enzymatic creatinine methods with calibration traceable to IDMS. Laboratory personnel and clinicians can estimate GFR for children by using this
Alkaline picrate (“Jaffe”) methods
As the global market for creatinine is strongly dominated by alkaline picrate (“Jaffe”) methods, the influence of lower total protein concentrations in children remains a source of error in methods, regardless of whether or not they have been calibrated to be traceable to IDMS. Many routine methods use an approximate correction for the nonspecific contribution of total protein to a serum or plasma creatinine value by subtracting an “average” bias from all measured results. This average correction approach (called “compensation” by at least one IVD manufacturer) can be useful for adult samples with physiological concentration of total proteins. However, for infants and children with typically lower serum total protein concentrations than adults, the fixed correction may subtract too much from the measured creatinine concentration causing over-correction, an erroneously low creatinine result, and an erroneously high estimated GFR.
Some alkaline picrate (“Jaffe”) methods use other approaches to minimize the influence of protein interference on creatinine results. However, the difference in total protein between young children and adults may affect any alkaline picrate (“Jaffe”) method and cause erroneous creatinine results.
The combined effect of IDMS-traceable calibration and an erroneous correction for serum proteins can cause a relatively large error in the estimated GFR that is more pronounced in very young (ages <2 years) children.
At this time, there has not been any systematic investigation to develop modified coefficients for the Schwartz equation—nor any other pediatric equation—for use with alkaline picrate (“Jaffe”) creatinine methods that have calibration traceable to IDMS. Therefore, it is recommended not to estimate GFR for children when using an alkaline picrate (“Jaffe”) method with calibration traceable to IDMS.
In problem cases, a measured creatinine clearance or measured glomerular filtration rate may be indicated. Alternatively, serum/plasma cystatin C concentration may be considered as an alternative basis for GFR calculation. However, cystatin C methods are not standardized, and estimating equations are currently under evaluation.
Bilirubin and hemolysis interference
Caution should be used when the sample is hemolyzed or has elevated bilirubin. These interferents generally cause lower serum creatinine, but the magnitude varies with specific enzymatic or alkaline picrate (“Jaffe”) methods.
Delanghe JR. How to estimate GFR in children. Nephrol Dial Transplant. 2008 May 29. [E-pub ahead of print])
Dimeski G, McWhinney B, Jones B, et al. Extent of bilirubin interference with Beckman creatinine methods . Ann Clin Biochem 2008;45:91-92.
Owen LJ, Keevil BG. Does bilirubin cause interference in Roche creatinine methods? Clin Chem 2007;53(2):370-1.
Wuyts B, Bernard D, Van Den Noortgate N, et al. Reevaluation of formulas for predicting creatinine clearance in adults and children using compensated creatinine methods. Clin Chem 2003;49:1011-1014.