Self-reported Race, Serum Creatinine, Cystatin C, and GFR in Children and Young Adults With Pediatric Kidney Diseases: A Report From the Chronic Kidney Disease in Children (CKiD) Study

Abstract

Rationale & objective: Recent reassessment of the use of race in estimated glomerular filtration rate (eGFR) in adults has instigated questions about the role of race in eGFR expressions for children. Little research has examined the associations of self-reported race with measured GFR (mGFR) adjusting for serum creatinine or cystatin C in children and young adults with chronic kidney disease (CKD). This study examined these associations and evaluated the performance of the previously published "U25" (under the age of 25 years) eGFR equations in a large cohort of children and young adults with CKD.

Study design: Observational cohort study.

Setting & participants: Participants in the Chronic Kidney Disease in Children (CKiD) study including 190 Black and 675 non-Black participants contributing 473 and 1,897 annual person-visits, respectively.

Exposure: Self- or parental-reported race (Black, non-Black). Adjustment for serum creatinine or cystatin C, body size, and socioeconomic status.

Outcome: mGFR based on iohexol clearance.

Analytical approach: Linear regression with generalized estimating equations, stratified by age (<6, 6-12, 12-18, and ≥18 years) incorporating serum creatinine or serum cystatin C. Contrasting performance in different self-reported racial groups of the U25 eGFR equations.

Results: Self-reported Black race was significantly associated with 12.8% higher mGFR among children in regression models including serum creatinine. Self-reported Black race was significantly associated with 3.5% lower mGFR after adjustment for cystatin C overall but was not significant for those over 12 years. The results were similar after adjustment for body size and socioeconomic factors. The average of creatinine- and cystatin C-based U25 equations was unbiased by self-reported race groups.

Limitations: Small number of children < 6 years; lean body mass was estimated.

Conclusions: Differences in the creatinine-mGFR relationship by self-reported race were observed in children and young adults with CKD and were consistent with findings in adults. Smaller and opposite differences were observed for the cystatin C-mGFR relationship, especially in the younger age group. We recommend inclusion of children for future investigations of biomarkers to estimate GFR. Importantly, for GFR estimation among those under 25 years of age, the average of the new U25 creatinine and cystatin C equations without race coefficients yields unbiased estimates of mGFR.

Keywords: Accuracy; CKD diagnosis; Tanner stage; adolescents; bias; body size; children; chronic kidney disease (CKD); estimated GFR (eGFR); glomerular filtration rate (GFR); lean body mass (LBM); measured GFR (mGFR); pediatric; race; race coefficient; racial differences; renal function; serum creatinine; serum cystatin C; young adult.

Figure 1.

The relationship between serum creatinine (x-axis) and directly measured iohexol GFR (y-axis) by race (Black/non-Black), stratified by age groups. Data points represent person-visits with nonparametric Lowess splines over the middle 95% of the serum creatinine data (dashed are Black race, and continuous are non-Black race). Ellipses represent the region encompassing 90% of the data, stratified by race. Both serum creatinine and iohexol GFR are plotted on the log scale.

Figure 2.

The relationship between serum cystatin c (x-axis) and directly measured iohexol GFR (y-axis) by race (Black/non-Black), stratified by age in 5 year bins. Data points represent person-visits with nonparametric Lowess splines over the middle 95% of the serum cystatin c data (dashed are Black race, and continuous are non-Black race). Ellipses represent the region encompassing 90% of the data, stratified by race. Both serum cystatin c and iohexol GFR are plotted on the log scale.

Figure 3.

Percent differences in GFR for Black with mixed race, and Black with no mixed race, relative to non-Black participants when conditioning on serum creatinine (Panel A), and serum cystatin C (Panel B), overall and stratified by age category. Estimates additionally adjust for age (on the continuous scale), sex, height, family income category, and college or more maternal education. Due to sparse data, differences for Black with mixed race were not estimated for age < 6 years (n= 6 person-visits) and ≥ 18 years (n= 14 person-visits).