title: Cystatin C and Cardiac Measures in Children and Adolescents With CKD.
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.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  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.
  
  
  METHODS
  Serum cystatin C (mg/L) measured annually.
  
  
  RESULTS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pediatric Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: tbrady8@jhmi.edu.
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Brady
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Kelly
authors.initials: K
authors.lastname: Townsend
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Schneider
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Christopher
authors.initials: C
authors.lastname: Cox
authors.affiliation: Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kimball
authors.affiliation: Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Peace
authors.initials: P
authors.lastname: Madueme
authors.affiliation: Division of Pediatric Nephrology, Children's Mercy Hospital, Kansas City, MO.
authors.forename: Bradley
authors.initials: B
authors.lastname: Warady
authors.affiliation: Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Susan
authors.initials: S
authors.lastname: Furth
authors.affiliation: Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Mark
authors.initials: M
authors.lastname: Mitsnefes
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D055316:Cystatin C / Q000097:blood*; D003971:Diastole; D004452:Echocardiography; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D055316:Cystatin C
keywords: Biomarker; adolescents; 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