Glomerular filtration rate (GFR) is a measure of how well the kidneys filter blood and is considered the best overall index of kidney function. Measured GFR (mGFR) can be calculated from the plasma or urinary clearance of exogenous filtration markers that are either infused or given as a single bolus. While mGFR is considered the gold standard and most accurate approximation to true GFR, it is an invasive and time-consuming study with technical challenges and problems with compliance (1). A more accessible, cost and time-effective approach consists of the use of equations that give an estimated GFR (eGFR) from measured concentration of endogenous markers, such as creatinine and cystatin C.
The CKD-EPI creatinine eGFR equation is the most widely used in adult populations for kidney function monitoring, with new guidelines recommending the removal of the race correction factor from the equation (2). While the debate on race correction was not of concern for eGFR equations used in pediatric population, estimation of GFR in the pediatric group faces its own challenges. Assessment of kidney function in children must consider the wide variation in muscle mass and the changes in creatinine reference ranges with age and sex in this group (3). To overcome this limitation, some equations developed to estimate GFR incorporate cystatin C, which is independent of muscle mass (4). Nevertheless, the existing equations for pediatric population have been mainly developed within cohorts that have chronic kidney disease and need further evaluation in children with normal kidney function (4). Consequently, even when plasma measurements used to estimate GFR are available, reporting eGFR together with laboratory results is still not widely implemented for children.
Aiming to select an equation to estimate GFR and report the calculation with laboratory measurements offered at our institution to assess kidney function, we conducted a retrospective study in a pediatric cohort from a diverse ethnicity, age, and disease states. We compared the performance of several eGFR equations with the mGFR calculated from multiple blood sample collection after intravenous tracer injection (Tc-99mDTPA). The best overall performances with the highest correlations, the lowest biases, and the highest percent within the 30% error (P30) from mGFR were obtained using the CKiD (4) and CKD-EPI CysC (5) equations. More recently, the Under 25 (U25) eGFR equations have been proposed for the use in pediatric and young adult populations, but guidelines are yet to be implemented (6).
In our study, the performances of these equations were lower than in the original studies, perhaps due to the diversity in ethnicity, age, diseases states of our cohort and the comparison to an mGFR derived from a different tracer. Assay standardization of creatinine and cystatin C traceable to their respective reference materials should provide more consistency in results across different laboratories and open avenue to further explore the performance of the existing equations and development of new equations in multiethnic groups, especially in pediatric population. Implementation of equations to estimate GFR in pediatric population should be offered by the laboratory whenever plasma measurements used to estimate GFR are available. They can provide insightful information about the patient’s changes in renal function over time and guide management. The selection of the appropriate equation to implement should be done in collaboration with the clinical team and will depend on the tests offered at the institution, test utilization, and the overall performance of the equation. Notably, while the equations are not definitive, they offer a better screening strategy to identify those at risk.
- Seegmiller JC, Eckfeldt JH, Lieske JC. Challenges in Measuring Glomerular Filtration Rate: A Clinical Laboratory Perspective. Adv Chronic Kidney Dis 2018;25:84-92.
- Delgado C, Baweja M, Crews DC, Eneanya ND, Gadegbeku CA, Inker LA, Mendu ML, et al. A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. Am J Kidney Dis 2021 Sep 22. Epub 2021/09/27 as doi: 10.1053/j.ajkd.2021.08.003.
- Schwartz GJ, Work DF. Measurement and estimation of GFR in children and adolescents. Clin J Am Soc Nephrol 2009;4:1832-43.
- Schwartz GJ, Schneider MF, Maier PS, Moxey-Mims M, Dharnidharka VR, Warady BA, Furth SL, et al. Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney Int 2012;82:445-53.
- Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, Kusek JW, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 2012;367:20-9.
- Pierce CB, Muñoz A, Ng DK, Warady BA, Furth SL, Schwartz GJ. Age- and sex-dependent clinical equations to estimate glomerular filtration rates in children and young adults with chronic kidney disease. Kidney Int. 2021 Apr;99(4):948-956.