Self-reported Race and GFR in Children and Young Adults

The best measure of kidney health is glomerular filtration rate (GFR). Recent reassessment of the use of race in estimated GFR (eGFR) in adults has raised questions regarding the role of race in equations used to calculate eGFR in children and young adults.

Pediatric eGFR equations from the Chronic Kidney Disease in Children (CKiD) cohort do not have a coefficient for Black race, including recent equations designed for patients under 25 years of age (U25 equations). There are few data available on 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).

Data from the CKiD study offer an opportunity to examine the biomarkers in that patient population, using centrally measured GFR, serum creatinine, and serum cystatin-C to assess putative differences in the biomarkers across ages and levels of kidney function in the context of self- and parental-reported race. Derek K. Ng, PhD, and colleagues reported results of an observational cohort study examining the differences. The researchers also sought to evaluate the performance of U25 equations in a large cohort of children and young adults with CKD. Results of the study were reported in the American Journal of Kidney Diseases [2022;80(2):174-185].

The study cohort included 190 Black and 675 non-Black participants in the CKiD study, representing 473 and 1897 annual person-visits, respectively. The study exposure was self- or parental-reported race (Black, non-Black). Analyses were adjusted for serum creatinine, cystatin-C, body size, and socioeconomic status. The outcome of interest was mGFR based on iohexol clearance.

Linear regression models were fit with mGFR as the dependent variable and serum creatinine as an independent variable, with additional independent variables for Black race and body size metrics. Each body size variable was included separately (none, sex, age as a continuous variable, height , body surface area, and estimated lean body mass [eLBM] without and with ancestry).

Both groups (Black and non-Black) were similar in age distribution (median age, 9 years) and in proportions of male participants (66.2% among Black person-visits and 61.3% among non-Black person-visits). Of the participants who self-reported Black race, 22.6% self-reported mixed race. Of the non-Black participants, 85.0% self-reported White race, and 5.6% reported non-Black mixed race.

Black participants were more likely to report household income less than $36,000 (65.5% vs 33.3%) and a maternal education level of less than college (77.0% vs 64.6%). Body size and Tanner stage were similar; however, the average eLBM was greater among Black participants. The two groups were similar in median serum creatinine (1.2 mg/dL), but serum cystatin-C was lower in Black versus non-Black participants (1.51 vs 1.73 mg/dL, respectively). Median mGFR was higher in Black participants than in non-Black participants (52.9 vs 46.2 mL/min1.73 m²).

In analyses of the association of self-reported race, mGFR, and serum creatinine, in unadjusted models without age stratification, mGFR was 12.8% (95% CI, 7.8%-18.1%) higher in Black participants. When models were fit by age groups older than 6 years, the difference ranged from +10% to +13.4%; the differences were significant for all older-than-6 age groups. In children younger than 6 years, the difference was similar but did not reach statistical significance (+7.4%; 95% CI, –1.0% to +16.5%); there was no statistical difference across age groups (P=.7).

In models assessing the relationship between serum cystatin-C and mGFR, there were minimal differences observed between Black and non-Black person-visits. Among participants younger than 6 years of age, Black person-visits had systematically (slightly) lower mGFR values, adjusting for serum cystatin C; the differences diminished in older age groups.

In regression models that included serum cystatin C, across all age groups in the unadjusted model, Black race was associated with lower mGFR (percent difference, –3.5% [95% CI, –5.7% to –1.4%]). There was no interaction across ages, but differences were attenuated as age increased: for ages 6 to 12, 12 to 18, and >18 years, the differences were –5.0% (95% CI, –8.3% to –1.5%), –2.5% (95% CI, –5.6% to +0.6%), and –0.9% (95% CI, –6.4% to +5.0%), respectively.

When other markers of body size and indicators of socioeconomic status were used as variables, the relationships remained essentially the same. Among participants under 6 years of age, self-reported Black race was consistently associated with mGFR (range, –7.5% to –9.3%). For those older than 18 years of age, nonsignificant differences ranged from –0.3% to –3.3%. There were similar associations across ages in multivariable models, but there were no interactions by age group.

There were some limitations to the study findings cited by the authors, including the lack of directly measured muscle mass, the possibility that the participant- or parent-reported question on race may have been interpreted differently by respondents, adjusting for only two socioeconomic variables (household income and maternal education), the small number of children under 6 years of age, and the lack of data on dietary patterns.

In conclusion, the researchers said, “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 estimated of mGFR.”

Takeaway Points

1. Researchers conducted a observational cohort study to examine relationships of self-reported race with measured glomerular filtration rate (mGFR) adjusting for serum creatinine or cystatin C in children and young adults with chronic kidney disease (CKD).
2. Following adjustment for serum creatinine, there was an association between self-reported Black race and slightly higher GFR in children more than 6 years of age and in young adults; following adjustment for cystatin C, there was a smaller and opposite difference.
3. The average of creatinine- and cystatin C-based equations designed for populations under the age of 25 was unbiased by self-reported race groups.