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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 174-185.e1 |
| Journal | American Journal of Kidney Diseases |
| Volume | 80 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 2022 |
Bibliographical note
Funding Information:The CKiD Study ( https://statepi.jhsph.edu/ckid ) is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (grants U01 DK066143, U01 DK066174, U24 DK082194, U24 DK066116). Data in this manuscript were collected by CKiD with clinical coordinating centers at Children’s Mercy Hospital and the University of Missouri, Kansas City (Principal Investigator [PI], Warady) and Children’s Hospital of Philadelphia (PI, Furth), Central Biochemistry Laboratory (PI, Schwartz) at the University of Rochester Medical Center, and data coordinating center (PIs, Muñoz and Ng) at the Johns Hopkins Bloomberg School of Public Health. The funders did not have any role in study design, data collection, analysis, reporting, or the decision to submit for publication.
Funding Information:
A list of the CKiD Study Investigators can be found in Table S5 and at https://statepi.jhsph.edu/ckid/site-investigators/. Derek K. Ng, PhD, Susan L. Furth, MD, PhD, Bradley A. Warady, MD, Deidra C. Crews, MD, ScM, Jesse C. Seegmiller, PhD, and George J. Schwartz, MD. Study concept: DKN, SLF, GJS; study design and data collection: DKN, GJS, BAW, SLF, JCS; statistical analysis: DKN; data interpretation: GJS, SLF, JCS, BAW, DCC. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual's own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. The CKiD Study ( https://statepi.jhsph.edu/ckid) is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (grants U01 DK066143, U01 DK066174, U24 DK082194, U24 DK066116). Data in this manuscript were collected by CKiD with clinical coordinating centers at Children's Mercy Hospital and the University of Missouri, Kansas City (Principal Investigator [PI], Warady) and Children's Hospital of Philadelphia (PI, Furth), Central Biochemistry Laboratory (PI, Schwartz) at the University of Rochester Medical Center, and data coordinating center (PIs, Muñoz and Ng) at the Johns Hopkins Bloomberg School of Public Health. The funders did not have any role in study design, data collection, analysis, reporting, or the decision to submit for publication. The authors declare that they have no relevant financial interests. The authors acknowledge Dr Rick Kaskel for critical input in the manuscript preparation, and Dr Alvaro Muñoz and Mr Christopher Pierce for their contributions to the evaluation of differences in U25 eGFR equations. Received April 29, 2021. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor and an Associate Editor, who served as Acting Editor-in-Chief. Accepted in revised form October 24, 2021. The involvement of an Acting Editor-in-Chief was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.
Publisher Copyright:
© 2022 National Kidney Foundation, Inc.
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
