Ceramides and cardiac function in children with chronic kidney disease

• Published in: Pediatric nephrology (Berlin, West) Vol. 29; no. 3; pp. 415 - 422
• Main Authors: Mitsnefes, Mark, Scherer, Philipp E., Friedman, Lisa Aronson, Gordillo, Ruth, Furth, Susan, Warady, Bradley A
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2014; Springer; Springer Nature B.V
• Subjects: Adolescent; Biomarkers - blood; Cardiac function; Cardiomyopathy; Case-Control Studies; Ceramides; Ceramides - blood; Child; Child, Preschool; Chronic kidney failure; Complications and side effects; Development and progression; Echocardiography, Doppler; Female; Health aspects; Health care; Humans; Hypertrophy, Left Ventricular - diagnostic imaging; Hypertrophy, Left Ventricular - etiology; Hypertrophy, Left Ventricular - physiopathology; Infant; Kidney diseases; Laboratories; Lactosylceramides - blood; Linear Models; Male; Medicine; Medicine & Public Health; Metabolites; Multivariate Analysis; Myocardial Contraction; Nephrology; North America; Original Article; Patient outcomes; Pediatrics; Pilot Projects; Prospective Studies; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - diagnosis; Risk Factors; Up-Regulation; Urology; Ventricular Dysfunction, Left - diagnostic imaging; Ventricular Dysfunction, Left - etiology; Ventricular Dysfunction, Left - physiopathology; Ventricular Function, Left; United States; United States > US; Heart; Heart failure; Ceramides; Lipids; Sphingolipids; CKD
• ISSN: 0931-041X; 1432-198X; 1432-198X
• DOI: 10.1007/s00467-013-2642-1

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 log 10 C24:0L and log 10 C16:0L 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.