How is kidney function assessed in children?

A:As in adults, measured glomerular filtration rate (mGFR) is considered the best overall index of kidney function in pediatric health and disease. GFR is measured by determining the clearance of an ideal filtration marker (e.g., inulin, iohexol, and iothalamate). These procedures may be complex and time consuming, which limits their availability and use in routine clinical practice. As a result, estimated GFR (eGFR) is commonly used.

Importantly, equations used to estimate GFR differ between adults and children. More than 10 equations currently exist for determining pediatric eGFR. Some are based on serum creatinine or cystatin C individually, and others include a combination of biomarkers. Pediatric eGFR equations commonly account for other variables, such as age, sex, and height or weight. Estimating equations that include a combination of biomarkers correlate better with mGFR, when compared to eGFR equations that employ only creatinine or cystatin C.

What is the best eGFR equation to use in children?

Currently, the best equations for estimating GFR in children are those developed and validated within the CKiD (Chronic Kidney Disease in Children) study cohorts, published in 2009 and 2012. Commonly referred to as the CKiD Schwartz equations, these incorporate serum creatinine (Scr), cystatin C (Scys) and blood urea nitrogen (BUN) with variables for height and sex.

When using eGFR equations, it is imperative to remember that an equation performs best when applied to a similar patient population and using measurement methods that are equivalent to those used in the equation’s development. The CKiD Schwartz equations were developed using data from children with chronic kidney disease and an isotope dilution mass spectrometry (IDMS)-traceable enzymatic creatinine method. They have been optimized for the type of cystatin C assay used (e.g. 2009 CKiD Schwartz for turbidimetric cystatin C and 2012 CKiD Schwartz for nephelometric cystatin C). The 2009 Schwartz CKiD is the most widely used multivariate pediatric eGFR equation: 39.1 x [height (m) / Scr (mg/dL)]0.516 × [1.8 / Scys (mg/L)]0.294 × [30 / BUN (mg/dL)]0.169 × 1.099male × [height (m) / 1.4]0.188

If measurement of cystatin C is not readily available, what is the best creatinine-based eGFR equation for use in children?

In children, the most frequently used creatinine-based eGFR equation is the revised bedside Schwartz: [(0.413 × Height (cm)) / Scr (mg/dL)]. This is recommended by the National Kidney Disease Education Program for use with creatinine methods with calibration traceable to IDMS.

Unlike the original bedside Schwartz [(k × Height (cm)) / Scr (mg/dL), k varies by age and sex], the revised bedside equation does not account for sex differences, even though beginning in early adolescence, factors affecting creatinine generation are known to differ between sexes, potentially impacting accuracy of eGFR.

Changes in creatinine measurement and calibration over time caused the original Schwartz equation to overestimate GFR compared with the mGFR. Use of an IDMS-traceable creatinine value with the original Schwartz equation will overestimate GFR by 20–40%.

Despite its convenience, there is room for improvement in the accuracy of the revised bedside Schwartz equation, and new eGFR equations are continually being investigated for use in pediatrics.

Brenda Suh-Lailam, PhD, is an assistant director of clinical chemistry and mass spectrometry at Ann & Robert H. Lurie Children’s Hospital of Chicago, and an assistant professor of pathology at Northwestern University Feinberg School of Medicine in Chicago, Ill.