Cystatin C and Cardiac Measures in Children and Adolescents With CKD

Tammy McLoughlin Brady, Kelly Townsend, Michael Schneider, Christopher Cox, Thomas Kimball, Peace Madueme, Bradley Warady, Susan Furth, Mark Mitsnefes

Research output: Contribution to journalArticle

Abstract

Background: Cardiovascular disease (CVD) is highly prevalent among children with chronic kidney disease (CKD). Cystatin C is an established marker of kidney function and an emerging biomarker for CVD events. We quantified the relationship between cystatin C level and cardiac structure and function over time among children with CKD and assessed whether cystatin C level and diastolic function retained an association after accounting for kidney function. Study Design: Prospective cohort study. Setting & Participants: 678 children and adolescents with mild to moderate CKD enrolled in the CKD in Children (CKiD) Study with 1,228 echocardiographically obtained cardiac structure and function measurements. Predictor: Serum cystatin C (mg/L) measured annually. Outcomes: Cardiac structure (left ventricular mass index [g/m2.7]) and cardiac function (shortening fraction; E/A, E'/A', E/E' ratios) measured every other year. Measurements: Demographics and anthropometrics, measured glomerular filtration rate (mGFR), heart rate, blood pressure, hemoglobin. z score, serum albumin level, and calcium-phosphorus product. Results: Independent of time, each 1-mg/L increase in cystatin C level was independently associated with a concurrent 7.7% (95% CI, 5.3%-10.0%) increase in left ventricular mass index, a -4.7% (95% CI, -7.0% to -2.4%) change in E/A ratio, a -6.6% (95% CI, -9.0% to -4.2%) change in E'/A' ratio, and a 2.5% (95% CI, 0.3%-4.7%) increase in E/E' ratio. mGFR was also independently associated with E'/A' ratio. When cystatin C level and mGFR were included in the same model, cystatin C level remained independently associated with E'/A' ratio, whereas mGFR was not. Limitations: 24% of the cohort was missing data for outcomes of interest or measurements; study population includes only children and adolescents with mild to moderate CKD. Conclusions: In this study of children and adolescents with mild to moderate CKD, cystatin C level was independently associated with cardiac structure and diastolic function. Cystatin C level remained able to predict diastolic function decline via E'/A' ratio even after adjusting for mGFR, suggesting that cystatin C level may have an independent role in CVD risk stratification among children and adolescents with CKD.

Original languageEnglish (US)
JournalAmerican Journal of Kidney Diseases
DOIs
StateAccepted/In press - Feb 18 2016

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Cystatin C
Chronic Renal Insufficiency
Glomerular Filtration Rate
Cardiovascular Diseases
Kidney
Only Child
Serum Albumin
Phosphorus
Hemoglobins
Cohort Studies
Biomarkers
Heart Rate
Demography
Prospective Studies
Blood Pressure
Calcium

Keywords

  • Adolescents
  • Biomarker
  • Cardiac function
  • Cardiac structure
  • Cardiovascular disease (CVD)
  • Children
  • Chronic kidney disease (CKD)
  • Cystatin C
  • Echocardiograph
  • Left ventricular hypertrophy (LVH)
  • Left ventricular mass (LVM)
  • Pediatrics
  • Renal function
  • Systolic function

ASJC Scopus subject areas

  • Nephrology

Cite this

Cystatin C and Cardiac Measures in Children and Adolescents With CKD. / Brady, Tammy McLoughlin; Townsend, Kelly; Schneider, Michael; Cox, Christopher; Kimball, Thomas; Madueme, Peace; Warady, Bradley; Furth, Susan; Mitsnefes, Mark.

In: American Journal of Kidney Diseases, 18.02.2016.

Research output: Contribution to journalArticle

Brady, Tammy McLoughlin ; Townsend, Kelly ; Schneider, Michael ; Cox, Christopher ; Kimball, Thomas ; Madueme, Peace ; Warady, Bradley ; Furth, Susan ; Mitsnefes, Mark. / Cystatin C and Cardiac Measures in Children and Adolescents With CKD. In: American Journal of Kidney Diseases. 2016.
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abstract = "Background: Cardiovascular disease (CVD) is highly prevalent among children with chronic kidney disease (CKD). Cystatin C is an established marker of kidney function and an emerging biomarker for CVD events. We quantified the relationship between cystatin C level and cardiac structure and function over time among children with CKD and assessed whether cystatin C level and diastolic function retained an association after accounting for kidney function. Study Design: Prospective cohort study. Setting & Participants: 678 children and adolescents with mild to moderate CKD enrolled in the CKD in Children (CKiD) Study with 1,228 echocardiographically obtained cardiac structure and function measurements. Predictor: Serum cystatin C (mg/L) measured annually. Outcomes: Cardiac structure (left ventricular mass index [g/m2.7]) and cardiac function (shortening fraction; E/A, E'/A', E/E' ratios) measured every other year. Measurements: Demographics and anthropometrics, measured glomerular filtration rate (mGFR), heart rate, blood pressure, hemoglobin. z score, serum albumin level, and calcium-phosphorus product. Results: Independent of time, each 1-mg/L increase in cystatin C level was independently associated with a concurrent 7.7{\%} (95{\%} CI, 5.3{\%}-10.0{\%}) increase in left ventricular mass index, a -4.7{\%} (95{\%} CI, -7.0{\%} to -2.4{\%}) change in E/A ratio, a -6.6{\%} (95{\%} CI, -9.0{\%} to -4.2{\%}) change in E'/A' ratio, and a 2.5{\%} (95{\%} CI, 0.3{\%}-4.7{\%}) increase in E/E' ratio. mGFR was also independently associated with E'/A' ratio. When cystatin C level and mGFR were included in the same model, cystatin C level remained independently associated with E'/A' ratio, whereas mGFR was not. Limitations: 24{\%} of the cohort was missing data for outcomes of interest or measurements; study population includes only children and adolescents with mild to moderate CKD. Conclusions: In this study of children and adolescents with mild to moderate CKD, cystatin C level was independently associated with cardiac structure and diastolic function. Cystatin C level remained able to predict diastolic function decline via E'/A' ratio even after adjusting for mGFR, suggesting that cystatin C level may have an independent role in CVD risk stratification among children and adolescents with CKD.",
keywords = "Adolescents, Biomarker, Cardiac function, Cardiac structure, Cardiovascular disease (CVD), Children, Chronic kidney disease (CKD), Cystatin C, Echocardiograph, Left ventricular hypertrophy (LVH), Left ventricular mass (LVM), Pediatrics, Renal function, Systolic function",
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T1 - Cystatin C and Cardiac Measures in Children and Adolescents With CKD

AU - Brady, Tammy McLoughlin

AU - Townsend, Kelly

AU - Schneider, Michael

AU - Cox, Christopher

AU - Kimball, Thomas

AU - Madueme, Peace

AU - Warady, Bradley

AU - Furth, Susan

AU - Mitsnefes, Mark

PY - 2016/2/18

Y1 - 2016/2/18

N2 - Background: Cardiovascular disease (CVD) is highly prevalent among children with chronic kidney disease (CKD). Cystatin C is an established marker of kidney function and an emerging biomarker for CVD events. We quantified the relationship between cystatin C level and cardiac structure and function over time among children with CKD and assessed whether cystatin C level and diastolic function retained an association after accounting for kidney function. Study Design: Prospective cohort study. Setting & Participants: 678 children and adolescents with mild to moderate CKD enrolled in the CKD in Children (CKiD) Study with 1,228 echocardiographically obtained cardiac structure and function measurements. Predictor: Serum cystatin C (mg/L) measured annually. Outcomes: Cardiac structure (left ventricular mass index [g/m2.7]) and cardiac function (shortening fraction; E/A, E'/A', E/E' ratios) measured every other year. Measurements: Demographics and anthropometrics, measured glomerular filtration rate (mGFR), heart rate, blood pressure, hemoglobin. z score, serum albumin level, and calcium-phosphorus product. Results: Independent of time, each 1-mg/L increase in cystatin C level was independently associated with a concurrent 7.7% (95% CI, 5.3%-10.0%) increase in left ventricular mass index, a -4.7% (95% CI, -7.0% to -2.4%) change in E/A ratio, a -6.6% (95% CI, -9.0% to -4.2%) change in E'/A' ratio, and a 2.5% (95% CI, 0.3%-4.7%) increase in E/E' ratio. mGFR was also independently associated with E'/A' ratio. When cystatin C level and mGFR were included in the same model, cystatin C level remained independently associated with E'/A' ratio, whereas mGFR was not. Limitations: 24% of the cohort was missing data for outcomes of interest or measurements; study population includes only children and adolescents with mild to moderate CKD. Conclusions: In this study of children and adolescents with mild to moderate CKD, cystatin C level was independently associated with cardiac structure and diastolic function. Cystatin C level remained able to predict diastolic function decline via E'/A' ratio even after adjusting for mGFR, suggesting that cystatin C level may have an independent role in CVD risk stratification among children and adolescents with CKD.

AB - Background: Cardiovascular disease (CVD) is highly prevalent among children with chronic kidney disease (CKD). Cystatin C is an established marker of kidney function and an emerging biomarker for CVD events. We quantified the relationship between cystatin C level and cardiac structure and function over time among children with CKD and assessed whether cystatin C level and diastolic function retained an association after accounting for kidney function. Study Design: Prospective cohort study. Setting & Participants: 678 children and adolescents with mild to moderate CKD enrolled in the CKD in Children (CKiD) Study with 1,228 echocardiographically obtained cardiac structure and function measurements. Predictor: Serum cystatin C (mg/L) measured annually. Outcomes: Cardiac structure (left ventricular mass index [g/m2.7]) and cardiac function (shortening fraction; E/A, E'/A', E/E' ratios) measured every other year. Measurements: Demographics and anthropometrics, measured glomerular filtration rate (mGFR), heart rate, blood pressure, hemoglobin. z score, serum albumin level, and calcium-phosphorus product. Results: Independent of time, each 1-mg/L increase in cystatin C level was independently associated with a concurrent 7.7% (95% CI, 5.3%-10.0%) increase in left ventricular mass index, a -4.7% (95% CI, -7.0% to -2.4%) change in E/A ratio, a -6.6% (95% CI, -9.0% to -4.2%) change in E'/A' ratio, and a 2.5% (95% CI, 0.3%-4.7%) increase in E/E' ratio. mGFR was also independently associated with E'/A' ratio. When cystatin C level and mGFR were included in the same model, cystatin C level remained independently associated with E'/A' ratio, whereas mGFR was not. Limitations: 24% of the cohort was missing data for outcomes of interest or measurements; study population includes only children and adolescents with mild to moderate CKD. Conclusions: In this study of children and adolescents with mild to moderate CKD, cystatin C level was independently associated with cardiac structure and diastolic function. Cystatin C level remained able to predict diastolic function decline via E'/A' ratio even after adjusting for mGFR, suggesting that cystatin C level may have an independent role in CVD risk stratification among children and adolescents with CKD.

KW - Adolescents

KW - Biomarker

KW - Cardiac function

KW - Cardiac structure

KW - Cardiovascular disease (CVD)

KW - Children

KW - Chronic kidney disease (CKD)

KW - Cystatin C

KW - Echocardiograph

KW - Left ventricular hypertrophy (LVH)

KW - Left ventricular mass (LVM)

KW - Pediatrics

KW - Renal function

KW - Systolic function

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U2 - 10.1053/j.ajkd.2016.08.036

DO - 10.1053/j.ajkd.2016.08.036

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