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.
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: Y T Zhou; P Grayburn; A Karim; M Shimabukuro; M Higa; D Baetens; L Orci; R H Unger Journal: Proc Natl Acad Sci U S A Date: 2000-02-15 Impact factor: 11.205
Authors: Ximena Lopez; Allison B Goldfine; William L Holland; Ruth Gordillo; Philipp E Scherer Journal: J Pediatr Endocrinol Metab Date: 2013 Impact factor: 1.634
Authors: Rebecca L Shaner; Jeremy C Allegood; Hyejung Park; Elaine Wang; Samuel Kelly; Christopher A Haynes; M Cameron Sullards; Alfred H Merrill Journal: J Lipid Res Date: 2008-11-25 Impact factor: 5.922
Authors: George J Schwartz; Alvaro Muñoz; Michael F Schneider; Robert H Mak; Frederick Kaskel; Bradley A Warady; Susan L Furth Journal: J Am Soc Nephrol Date: 2009-01-21 Impact factor: 10.121
Authors: Svjetlana Lovric; Sara Goncalves; Heon Yung Gee; Babak Oskouian; Honnappa Srinivas; Won-Il Choi; Shirlee Shril; Shazia Ashraf; Weizhen Tan; Jia Rao; Merlin Airik; David Schapiro; Daniela A Braun; Carolin E Sadowski; Eugen Widmeier; Tilman Jobst-Schwan; Johanna Magdalena Schmidt; Vladimir Girik; Guido Capitani; Jung H Suh; Noëlle Lachaussée; Christelle Arrondel; Julie Patat; Olivier Gribouval; Monica Furlano; Olivia Boyer; Alain Schmitt; Vincent Vuiblet; Seema Hashmi; Rainer Wilcken; Francois P Bernier; A Micheil Innes; Jillian S Parboosingh; Ryan E Lamont; Julian P Midgley; Nicola Wright; Jacek Majewski; Martin Zenker; Franz Schaefer; Navina Kuss; Johann Greil; Thomas Giese; Klaus Schwarz; Vilain Catheline; Denny Schanze; Ingolf Franke; Yves Sznajer; Anne S Truant; Brigitte Adams; Julie Désir; Ronald Biemann; York Pei; Elisabet Ars; Nuria Lloberas; Alvaro Madrid; Vikas R Dharnidharka; Anne M Connolly; Marcia C Willing; Megan A Cooper; Richard P Lifton; Matias Simons; Howard Riezman; Corinne Antignac; Julie D Saba; Friedhelm Hildebrandt Journal: J Clin Invest Date: 2017-02-06 Impact factor: 14.808
Authors: Michelle M Mielke; Norman J Haughey; Dingfen Han; Yang An; Veera Venkata Ratnam Bandaru; Constantine G Lyketsos; Luigi Ferrucci; Susan M Resnick Journal: J Alzheimers Dis Date: 2017 Impact factor: 4.472
Authors: Michelle M Mielke; Veera Venkata Ratnam Bandaru; Dingfen Han; Yang An; Susan M Resnick; Luigi Ferrucci; Norman J Haughey Journal: Aging Cell Date: 2015-07-20 Impact factor: 9.304
Authors: Georgios Grammatikos; Niklas Schoell; Nerea Ferreirós; Dimitra Bon; Eva Herrmann; Harald Farnik; Verena Köberle; Albrecht Piiper; Stefan Zeuzem; Bernd Kronenberger; Oliver Waidmann; Josef Pfeilschifter Journal: Oncotarget Date: 2016-04-05