Relationships of Measured Iohexol GFR and Estimated GFR With CKD-Related Biomarkers in Children and Adolescents

Abstract

Background: 2 valid and reliable estimated glomerular filtration rate (GFR) equations for the pediatric population have been developed from directly measured GFR data in the Chronic Kidney Disease in Children (CKiD) cohort: the full CKiD and bedside CKiD equations. Although adult GFR estimating equations replicate relationships of measured GFR with biomarkers, it is unclear whether similar patterns exist among children and adolescents with chronic kidney disease (CKD).

Study design: Prospective cohort study in children and adolescents.

Settings & participants: 730 participants contributed 1,539 study visits.

Predictors: Measured GFR by plasma iohexol disappearance (mGFR), estimated GFR by the full CKiD equation (eGFRCKiDfull; based on serum creatinine, cystatin C, serum urea nitrogen, height, and sex), and estimated GFR by the bedside CKiD equation (eGFRCKiDbed; calculated as 41.3 × height [m]/serum creatinine [mg/dL]) were predictors of CKD-related biomarkers. Deviations of mGFR from eGFRCKiDfull and deviations of eGFRCKiDfull from eGFRCKiDbed from linear regressions (ie, residuals) were included in bivariate analyses.

Outcomes & measurements: CKD-related biomarkers included values for urine protein-creatinine ratio, blood hemoglobin, serum phosphate, bicarbonate, potassium, systolic and diastolic blood pressure z scores, and height z scores.

Results: The median age of 730 participants with CKD was 12.5 years, with median mGFR, eGFRCKiDfull, and eGFRCKiDbed of 51.8, 54.0, and 53.2mL/min/1.73m2, respectively. eGFRCKiDfull demonstrated as strong or stronger associations with CKD-related biomarkers than mGFR; eGFRCKiDbed associations were significantly attenuated (ie, closer to the null). Residual information in mGFR did not substantially increase explained variability. eGFRCKiDbed estimated faster GFR decline relative to mGFR and eGFRCKiDfull.

Limitations: Simple linear summaries of biomarkers may not capture nonlinear associations.

Conclusions: eGFRCKiDfull closely approximated mGFR to describe relationships with CKD-severity indicators and progression in this pediatric CKD population. eGFRCKiDbed offered similar inferences, but associations were attenuated and rate of progression was overestimated. The eGFRCKiDfull equation from 2012 is preferred for pediatric research purposes.

Keywords: CKD biomarker; Chronic Kidney Disease in Children (CKiD); GFR estimating equation; Pediatric; adolescents; children; chronic kidney disease (CKD); estimated GFR; glomerular filtration rate (GFR); iohexol; kidney function; kidney measure; measured GFR.

Conflict of interest statement

N Section: Because an author of this article is an editor for AJKD, the peer-review and decision-making processes were handled by an Editorial Board Member (Kathleen Liu, MD, PhD) who served as Acting Editor-in-Chief. Details of the journal's procedures for potential editor conflicts are given in the Information for Authors & Journal Policies.

Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Diamond plot comparison of differences in naïve R2 values (in %) for univariate directly measured iohexol-based GFR (iGFR), serum creatinine, cystatin C and BUN-based estimated GFR (eGFR) and serum creatinine-based bedside GFR (bedGFR) and for bivariate models including iGFR and eGFR deviations (residuals) among 730 children and adolescents providing 1539 visits. R2 values are scaled to 25% (total area of each diamond).