Estimating the eGFR in Children and Young Adults
Estimating the eGFR in Children and Young Adults
Background. A new estimated glomerular filtration rate (eGFR) equation, designed for isotope dilution mass spectrometry-standardized serum creatinine (Scr), is presented for use in children, adolescent boys and girls and young adults.
Methods. The new equation, eGFR = 107.3/(Scr/Q), is based on the concept of normalized Scr: Q is the normalization value and is considered as the Scr concentration for the average healthy child, adolescent or young adult of a specific height (L) and is modeled as a height-dependent polynomial of the fourth degree.
Results. The well-known Schwartz equation [eGFR = kL/Scr, k = 0.413 (Schwartz) or k = 0.373 (Schwartz–Lyon)] for children between 1 and 14 years can be seen as a special case of the new equation for which the Q-polynomial is simplified to a linear equation: Q = 0.0035 × L (cm). The new eGFR equation has been validated in a data set of n = 750 children, adolescents and young adults aged 10–25, against the true GFR (inulin method), and outperforms the selected (but most used) creatinine-based eGFR equations for children, mainly in the healthy GFR region.
Conclusions. The new Q(height)-eGFR equation serves as an excellent screening tool for kidney disease in 1–25-year-old children, adolescents and young adults.
The glomerular filtration rate (GFR) is widely considered the best overall index of kidney function in health and disease. Because direct measurements of GFR cannot always be performed in clinical routine settings, formulas have been presented to estimate the GFR (eGFR). In those formulas, serum creatinine (Scr, expressed in mg/dL) is most commonly used as a marker for renal function.
In the last decade, new eGFR formulas have been developed for adults and children because of the evolution in laboratory testing of Scr to iotope dilution mass spectrometry (IDMS)-standardized techniques, but few attempts have been undertaken to develop new formulas for adolescents. Selistre et al. assessed multiple existing adult and pediatric creatinine-based eGFR equations in adolescents and young adults, using inulin clearance as the reference method. The adult eGFR formulas substantially overestimate the GFR, but better prediction performance was found for the pediatric equations. (An overview of the pediatric equations used in this study is given in Table 1 ). Selistre et al., therefore, recommend the use of pediatric equations, especially the updated Schwartz equation to estimate the GFR from childhood to early adulthood.
However, none of the pediatric equations have been developed to be used in the adolescent population. Moreover, these formulas do not differentiate between boys and girls, although there is an important difference in growth (height) and in Scr concentration between sexes ever since adolescence. This large variation in body shape and growth determines extreme variation in muscular mass and may be a dominant factor when developing eGFR formulas for this population.
In this paper, we demonstrate how a new eGFR formula for adolescents is constructed from a particular rationale, based on the knowledge of Scr for healthy adolescents, combined with the use of metadata. This rationale uses the concept of population-normalized Scr in which the normalization constant (Q) is the median or the average Scr concentration of a specific population of healthy people, be it children or adults. It has been shown that for adults between 18 and 65 years of age, the value of Q is a constant and equals 0.70 mg/dL for Caucasian females and 0.90 mg/dL for Caucasian males. For children, Q is the median Scr for healthy children and depends linearly on age. We extended this idea of normalized Scr to adolescents. By modeling Q as a function of age, we experienced different relationships for girls and boys, but when modeling Q as a function of height, we found a unique relationship between Q and height for both boys and girls. This Q(height) relationship forms the basis for a promising new eGFR equation suitable for children, adolescents and even young adults.
Abstract and Introduction
Abstract
Background. A new estimated glomerular filtration rate (eGFR) equation, designed for isotope dilution mass spectrometry-standardized serum creatinine (Scr), is presented for use in children, adolescent boys and girls and young adults.
Methods. The new equation, eGFR = 107.3/(Scr/Q), is based on the concept of normalized Scr: Q is the normalization value and is considered as the Scr concentration for the average healthy child, adolescent or young adult of a specific height (L) and is modeled as a height-dependent polynomial of the fourth degree.
Results. The well-known Schwartz equation [eGFR = kL/Scr, k = 0.413 (Schwartz) or k = 0.373 (Schwartz–Lyon)] for children between 1 and 14 years can be seen as a special case of the new equation for which the Q-polynomial is simplified to a linear equation: Q = 0.0035 × L (cm). The new eGFR equation has been validated in a data set of n = 750 children, adolescents and young adults aged 10–25, against the true GFR (inulin method), and outperforms the selected (but most used) creatinine-based eGFR equations for children, mainly in the healthy GFR region.
Conclusions. The new Q(height)-eGFR equation serves as an excellent screening tool for kidney disease in 1–25-year-old children, adolescents and young adults.
Introduction
The glomerular filtration rate (GFR) is widely considered the best overall index of kidney function in health and disease. Because direct measurements of GFR cannot always be performed in clinical routine settings, formulas have been presented to estimate the GFR (eGFR). In those formulas, serum creatinine (Scr, expressed in mg/dL) is most commonly used as a marker for renal function.
In the last decade, new eGFR formulas have been developed for adults and children because of the evolution in laboratory testing of Scr to iotope dilution mass spectrometry (IDMS)-standardized techniques, but few attempts have been undertaken to develop new formulas for adolescents. Selistre et al. assessed multiple existing adult and pediatric creatinine-based eGFR equations in adolescents and young adults, using inulin clearance as the reference method. The adult eGFR formulas substantially overestimate the GFR, but better prediction performance was found for the pediatric equations. (An overview of the pediatric equations used in this study is given in Table 1 ). Selistre et al., therefore, recommend the use of pediatric equations, especially the updated Schwartz equation to estimate the GFR from childhood to early adulthood.
However, none of the pediatric equations have been developed to be used in the adolescent population. Moreover, these formulas do not differentiate between boys and girls, although there is an important difference in growth (height) and in Scr concentration between sexes ever since adolescence. This large variation in body shape and growth determines extreme variation in muscular mass and may be a dominant factor when developing eGFR formulas for this population.
In this paper, we demonstrate how a new eGFR formula for adolescents is constructed from a particular rationale, based on the knowledge of Scr for healthy adolescents, combined with the use of metadata. This rationale uses the concept of population-normalized Scr in which the normalization constant (Q) is the median or the average Scr concentration of a specific population of healthy people, be it children or adults. It has been shown that for adults between 18 and 65 years of age, the value of Q is a constant and equals 0.70 mg/dL for Caucasian females and 0.90 mg/dL for Caucasian males. For children, Q is the median Scr for healthy children and depends linearly on age. We extended this idea of normalized Scr to adolescents. By modeling Q as a function of age, we experienced different relationships for girls and boys, but when modeling Q as a function of height, we found a unique relationship between Q and height for both boys and girls. This Q(height) relationship forms the basis for a promising new eGFR equation suitable for children, adolescents and even young adults.
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