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Peer-reviewedCC BY 4.0Frontiers in Endocrinology

Sphingolipid–renal interplay in coronary artery calcification: ceramide profiling and imaging validation from the CRUISE-MET study

  • Qiang Chen1,2
  • Sijia Guo3,4
  • Xuexi Li1,5
  • Yike Li1
  • Yingying Xie1
  • Sunjing Fu4,5
  • Ruoyun Ma5
  • Xiaxia Peng5
  • Sheng Xie3
  • Yanxiang Gao5
  • Jingang Zheng1,5
5 affiliations
  1. 1Department of Cardiology, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College
  2. 2Department of Cardiology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University
  3. 3Department of Radiology, China-Japan Friendship Hospital
  4. 4Peking University China-Japan Friendship School of Clinical Medicine
  5. 5Department of Cardiology, China-Japan Friendship Hospital
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Abstract

Background: Coronary artery calcification (CAC) represents a distinct imaging phenotype reflecting advanced vascular remodeling, particularly in patients with chronic kidney disease (CKD). However, metabolic determinants linking renal dysfunction to CAC remain incompletely understood. Ceramides, bioactive sphingolipids involved in vascular inflammation and calcification, may represent potential mediators of this interaction.

Methods: In this cross-sectional analysis of 851 coronary artery disease (CAD) patients from the CRUISE-MET trial (NCT06383208), six plasma ceramide species [Cer(18:1/16:0), (18:1/18:0), (18:1/20:0), (18:1/22:0), (18:1/24:0), and (18:1/24:1)] were quantified by UHPLC–MS/MS. CAC severity was classified angiographically as absent, mild, moderate, or severe. Logistic regression, ROC analysis, and restricted cubic splines assessed associations. Joint and mediation analyses examined interactions with CKD. Sensitivity analyses evaluated consistency across subgroups and in a cohort with non-ECG-gated chest CT–derived CAC scores.

Results: Patients with moderate-to-severe CAC had higher Cer(18:1/16:0), Cer(18:1/24:1), older age, higher SYNTAX scores, and lower estimated glomerular filtration rate (eGFR) (all p<0.05). Each SD increase in Cer(18:1/16:0) was associated with 59% higher odds of moderate-to-severe CAC (OR = 1.59, 95% CI: 1.33–1.88, p<0.001); the highest tertile was associated with 151% higher odds (OR = 2.51, 95% CI: 1.68–3.75, p<0.001). CKD modified this association (p for interaction=0.032), with coexisting CKD and high ceramide exposure yielding nearly fourfold higher odds (OR = 3.94, 95% CI: 2.47–6.28, p<0.001). Mediation analysis indicated Cer(18:1/16:0) accounted for 15.6% of the CKD–CAC association. Associations remained directionally consistent across sensitivity analyses. In the CT subgroup, modest associations were observed between selected ceramide species and quantitative CACS.

Conclusion: Specific ceramides, particularly Cer(18:1/16:0), are independently associated with CAC severity, with stronger associations observed in patients with CKD.

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Cite

BibTeXRIS
BibTeX
@article{chen2026sphingolipidrenal,
  title = {{Sphingolipid–renal interplay in coronary artery calcification: ceramide profiling and imaging validation from the CRUISE-MET study}},
  author = {Qiang Chen and Sijia Guo and Xuexi Li and Yike Li and Yingying Xie and Sunjing Fu and Ruoyun Ma and Xiaxia Peng and Sheng Xie and Yanxiang Gao and Jingang Zheng},
  journal = {Frontiers in Endocrinology},
  year = {2026},
  month = oct,
  doi = {10.3389/fendo.2026.1974775},
  url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1974775/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Sphingolipid–renal interplay in coronary artery calcification: ceramide profiling and imaging validation from the CRUISE-MET study
AU  - Qiang Chen
AU  - Sijia Guo
AU  - Xuexi Li
AU  - Yike Li
AU  - Yingying Xie
AU  - Sunjing Fu
AU  - Ruoyun Ma
AU  - Xiaxia Peng
AU  - Sheng Xie
AU  - Yanxiang Gao
AU  - Jingang Zheng
PY  - 2026
DA  - 2026/10/14
JO  - Frontiers in Endocrinology
DO  - 10.3389/fendo.2026.1974775
UR  - https://www.frontiersin.org/articles/10.3389/fendo.2026.1974775/full
AB  - Background: Coronary artery calcification (CAC) represents a distinct imaging phenotype reflecting advanced vascular remodeling, particularly in patients with chronic kidney disease (CKD). However, metabolic determinants linking renal dysfunction to CAC remain incompletely understood. Ceramides, bioactive sphingolipids involved in vascular inflammation and calcification, may represent potential mediators of this interaction.  Methods: In this cross-sectional analysis of 851 coronary artery disease (CAD) patients from the CRUISE-MET trial (NCT06383208), six plasma ceramide species [Cer(18:1/16:0), (18:1/18:0), (18:1/20:0), (18:1/22:0), (18:1/24:0), and (18:1/24:1)] were quantified by UHPLC–MS/MS. CAC severity was classified angiographically as absent, mild, moderate, or severe. Logistic regression, ROC analysis, and restricted cubic splines assessed associations. Joint and mediation analyses examined interactions with CKD. Sensitivity analyses evaluated consistency across subgroups and in a cohort with non-ECG-gated chest CT–derived CAC scores.  Results: Patients with moderate-to-severe CAC had higher Cer(18:1/16:0), Cer(18:1/24:1), older age, higher SYNTAX scores, and lower estimated glomerular filtration rate (eGFR) (all p<0.05). Each SD increase in Cer(18:1/16:0) was associated with 59% higher odds of moderate-to-severe CAC (OR = 1.59, 95% CI: 1.33–1.88, p<0.001); the highest tertile was associated with 151% higher odds (OR = 2.51, 95% CI: 1.68–3.75, p<0.001). CKD modified this association (p for interaction=0.032), with coexisting CKD and high ceramide exposure yielding nearly fourfold higher odds (OR = 3.94, 95% CI: 2.47–6.28, p<0.001). Mediation analysis indicated Cer(18:1/16:0) accounted for 15.6% of the CKD–CAC association. Associations remained directionally consistent across sensitivity analyses. In the CT subgroup, modest associations were observed between selected ceramide species and quantitative CACS.  Conclusion: Specific ceramides, particularly Cer(18:1/16:0), are independently associated with CAC severity, with stronger associations observed in patients with CKD.
SN  - 1664-2392
ER  -