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

Derek Ng, George J. Schwartz, Bradley A. Warady, Susan L. Furth, Alvaro Munoz

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalAmerican Journal of Kidney Diseases
DOIs
StateAccepted/In press - Oct 28 2016

Fingerprint

Iohexol
Glomerular Filtration Rate
Chronic Renal Insufficiency
Biomarkers
Creatinine
Pediatrics
Serum
Blood Pressure
Cystatin C
Population
Urea
Linear Models

Keywords

  • Adolescents
  • Children
  • Chronic kidney disease (CKD)
  • Chronic Kidney Disease in Children (CKiD)
  • CKD biomarker
  • Estimated GFR
  • GFR estimating equation
  • Glomerular filtration rate (GFR)
  • Iohexol
  • Kidney function
  • Kidney measure
  • Measured GFR
  • Pediatric

ASJC Scopus subject areas

  • Nephrology

Cite this

Relationships of Measured Iohexol GFR and Estimated GFR With CKD-Related Biomarkers in Children and Adolescents. / Ng, Derek; Schwartz, George J.; Warady, Bradley A.; Furth, Susan L.; Munoz, Alvaro.

In: American Journal of Kidney Diseases, 28.10.2016.

Research output: Contribution to journalArticle

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title = "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 = "Adolescents, Children, Chronic kidney disease (CKD), Chronic Kidney Disease in Children (CKiD), CKD biomarker, Estimated GFR, GFR estimating equation, Glomerular filtration rate (GFR), Iohexol, Kidney function, Kidney measure, Measured GFR, Pediatric",
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T1 - Relationships of Measured Iohexol GFR and Estimated GFR With CKD-Related Biomarkers in Children and Adolescents

AU - Ng, Derek

AU - Schwartz, George J.

AU - Warady, Bradley A.

AU - Furth, Susan L.

AU - Munoz, Alvaro

PY - 2016/10/28

Y1 - 2016/10/28

N2 - 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.

AB - 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.

KW - Adolescents

KW - Children

KW - Chronic kidney disease (CKD)

KW - Chronic Kidney Disease in Children (CKiD)

KW - CKD biomarker

KW - Estimated GFR

KW - GFR estimating equation

KW - Glomerular filtration rate (GFR)

KW - Iohexol

KW - Kidney function

KW - Kidney measure

KW - Measured GFR

KW - Pediatric

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