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.

Conflict of interest statement

Statement of competing financial interests No conflicts are reported.

Statement of non-financial competing interestsNo conflicts are reported.

Figures

Fig. 1

Comparison of total ceramide levels in healthy children and children with chronic kidney disease (CKD). Data were normalized to respective pooled normal human plasma control samples at time of each sphingolipid analysis: metabolite level in the sample was divided by average metabolite level in pooled normal plasma control

Fig. 2

Distribution of ceramides in healthy controls and children with chronic kidney disease (CKD). Significant differences were observed for all ceramide species (p <0.001) except C24:0 (p =0.11); Wilcoxon rank-sum test

Fig. 3

Comparison of individual ceramide levels in healthy children and children with chronic kidney disease (CKD). Data were normalized to respective pooled normal human plasma control samples at time of each sphingolipid analysis: metabolite level in the sample was divided by average metabolite level in pooled normal plasma control

Fig. 4

Distribution of lactosylceramides C16:0L and C24:0L in healthy controls and children with chronic kidney disease (CKD)