title: Ceramides and cardiac function in children with chronic kidney disease.
abstract: BACKGROUND
  Chronic kidney disease (CKD) is associated with increased incidence of cardiac dysfunction. Recent animal studies have demonstrated that elevated levels of ceramides cause dilated lipotoxic cardiomyopathy. We hypothesized ceramides are increased in children with CKD and associated with abnormal cardiac structure and function.
  
  
  METHODS
  Ceramide levels were determined in 93 children aged 1-16 years enrolled in the Chronic Kidney Disease in Children (CKiD) study and compared to levels from 24 healthy controls. Complete demographic, clinical, and laboratory information, and ceramide measurements were analyzed cross-sectionally. Echocardiography was performed to determine cardiac structure and function.
  
  
  RESULTS
  Very long-chain C24:0 ceramides were the most abundant species in both control (56 %) and CKD subjects (55 %), followed by C24:1 (controls 19 %, CKD 23 %) and C22:0 (controls 19 %, CKD 13 %). Total serum ceramide levels were significantly higher in CKD children versus controls (p < 0.001). Ceramide metabolites lactosylceramide, C24:0L, and C16:0L were significantly higher in CKD subjects than controls (p < 0.001). The proportion of C24:0L was dramatically higher in CKD (59 %) versus control (17 %) subjects (p < 0.001). In adjusted multivariate analyses, higher log10C24:0L and log10C16:0L were significant predictors of lower shortening fraction and mid-wall shortening.
  
  
  CONCLUSIONS
  Ceramide levels are increased in children with CKD. Our study identified lactosylceramides as an independent predictor of lower systolic function in these children.
authors.affiliation: Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, MLC: 7022, 3333 Burnet Avenue, Cincinnati, OH, 45229-3039, USA, mark.mitsnefes@cchmc.org.
authors.forename: Mark
authors.initials: M
authors.lastname: Mitsnefes
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.forename: Lisa Aronson
authors.initials: LA
authors.lastname: Friedman
authors.forename: Ruth
authors.initials: R
authors.lastname: Gordillo
authors.forename: Susan
authors.initials: S
authors.lastname: Furth
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Warady
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002518:Ceramides / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D015150:Echocardiography, Doppler; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D007223:Infant; D007790:Lactosylceramides / Q000097:blood; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D009200:Myocardial Contraction; D009656:North America; D010865:Pilot Projects; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D012307:Risk Factors; D015854:Up-Regulation; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D002518:Ceramides; D007790:Lactosylceramides