Age- and sex-dependent clinical equations to estimate glomerular filtration rates in children and young adults with chronic kidney disease

Abstract

Using data (2655 observations from 928 participants) from the Chronic Kidney Disease in Children Study, we developed and internally validated new glomerular filtration rate estimating equations for clinical use in children and young adults: two forms of K × [heigh(ht) / serum creatinine(sCr)] and two forms of K × [1 / cystatin C(cysC)]. For each marker, one equation used a sex-dependent K; in the other, K is sex-and age-dependent. Glomerular filtration rate (GFR) was measured directly by plasma iohexol disappearance. The equations using ht⁄sCr had sex-specific constants of 41.8 for males and 37.6 for females. In the age- dependent models, K increased monotonically for children 1-18 years old and was constant for young adults 18-25 years. For males, K ranged from 35.7 for one-year-olds to 50.8 for those 18 and older. For females, the values of K ranged from 33.1 to 41.4. Constant K values for cystatin-C equations were 81.9 for males and 74.9 for females. With age-dependency, K varied non-monotonically with the highest values at age 15 for males (K of 87.2) and 12 years for females (K of 79.9). Use of an age-dependent K with ht/sCr models reduced average bias, notably in young children and young adults; age-dependent cystatin-C models produced similar agreement to using a constant K in children under 18 years, but reduced bias in young adults. These age-dependent proposed equations were evaluated alongside estimated GFRs from 11 other published equations for pediatrics and young adults. Only our proposed equations yielded non- significant bias and within 30% accuracy values greater than 85% in both the pediatric and young adult subpopulations.

Keywords: chronic kidney disease; clinical nephrology; glomerular filtration rate; pediatric nephrology; young adults.

Figure 1|. Sex-specific values of K by age from the Chronic Kidney Disease in Children (CKiD) Study CKiD under 25 constant (dashed line) and age-dependent (solid line) models.

(a) The height/serum creatinine (sCr) models. (b) The cystatin-C (cysC) models. Scatterplot of training data (n = 1764 measurements from 618 participants) is superimposed. mGFR, measured glomerular filtration rate.

Figure 2|. Mean bias (percentage) of Chronic Kidney Disease in Children (CKiD) Study CKiD under 25 estimated glomerular filtration rate (GFR) versus iohexol-measured GFR by age and sex in the validation data set (n = 891 observations from 310 participants) for models using a constant K and an age-dependent K.

(a) Equations based on height/serum creatinine (sCr). (b) Equations based on cystatin-C (cysC). Solid squares represent point estimates; vertical bars represent the 95% confidence interval.

Figure 3|. Scatterplot of sex- and age-dependent Chronic Kidney Disease in Children (CKiD) Study CKiD under 25 (U25) estimated glomerular filtration rate (eGFR) versus iohexol-measured glomerular filtration rate (mGFR) in the validation data set.

(a) Height/serum creatinine (sCr)–based eGFR (n = 891 observations from 310 participants). (b) Cystatin-C–based eGFR (n = 843 observations from 304 participants). Solid line is reference line of equality; dashed line is regression line. Black dot marks the mean mGFR and mean U25 eGFR.