Guidelines for laboratories: Calculating estimated GFR for children
At this time, all laboratories should be using creatinine methods calibrated to be IDMS traceable. In the US and other countries, nearly all methods from the major global manufacturers now have calibration traceable to an IDMS reference measurement procedure. Consequently, the older equations for estimating glomerular filtration rate (GFR) in children and infants are no longer valid.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 causing estimates of GFR to be too high.
Below you will find information on the following topics as they relate to estimating GFR for children:
Potential problems following recalibration to be traceable to IDMS
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 some 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 have been performed to permit a modified Schwartz equation to be used with blood, serum, or plasma creatinine methods that have calibration traceable to IDMS. 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 Bedside Schwartz equation. Although the Bedside Schwartz equation was based on a single enzymatic creatinine method with calibration traceable to IDMS, it is expected to be suitable for use with other enzymatic as well as alkaline picrate ("Jaffe") methods with calibration traceable to IDMS. The equation provides a relationship between creatinine and GFR in the CKid population of children with kidney disease. Note that there may be important differences among methods regarding the influence of both endogenous (e.g., protein, ketone bodies, bilirubin, hemolysis) and exogenous (e.g., drugs) substances on the accuracy of a creatinine measurement for a given patient sample.
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 some 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. Note that there are differences among alkaline picrate ("Jaffe") methods regarding influence of protein on creatinine results.
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"). Further investigation is needed to more completely understand the influence of protein on commonly used methods for creatinine.
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.
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 estimation. However, cystatin C methods are not standardized, and published estimating equations are only suitable for the method and population used to develop the equation.
Bilirubin and hemolysis interference
Caution should be used when the sample is hemolyzed or has elevated bilirubin. These interferences generally cause lower serum creatinine, but the magnitude varies with specific enzymatic or alkaline picrate ("Jaffe") methods.
March 1, 2012