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Joint association of plasma ceramide and renal function with coronary artery lesion severity: The CRUISE-MET study

Qiang Chen1, Yike Li1, Haoming He1

  • 1Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (Drs Chen, Li, He, Xie, Yang, Zhou, and Zheng); Department of Cardiology, China-Japan Friendship Hospital, Beijing, China (Drs Chen, Li, He, Xie, D. Fu, Gao, Li, S. Fu, Mu, Sun, Yang, Zhou, Li, Gao, and Zheng).

Journal of Clinical Lipidology
|October 2, 2025
PubMed

Insights

Chronic kidney disease (CKD) and elevated ceramides, particularly Cer (18:1/16:0), synergistically increase the risk of complex coronary artery disease (CAD). This highlights the need for combined biomarker assessment and targeted therapies for atherosclerosis.

Area of Science:

  • Cardiovascular Medicine
  • Nephrology
  • Biochemistry

Background:

  • Ceramides and chronic kidney disease (CKD) are known independent risk factors for atherosclerosis.
  • The synergistic impact of ceramides and CKD on coronary lesion severity is not well understood.

Purpose of the Study:

  • To investigate the combined effect of specific ceramide species and renal dysfunction on coronary lesion complexity in patients with coronary artery disease (CAD).

Main Methods:

  • Cross-sectional analysis of 691 CAD patients from the CRUISE-MET trial.
  • Quantification of six ceramide species using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry.
  • Classification of complex CAD (bSS > 22) and CKD (based on eGFR and UACR).
  • Evaluation of combined and mediating effects of ceramides and renal dysfunction on coronary lesion complexity.

Main Results:

  • Patients with complex lesions had elevated UACR, specific ceramides (Cer (18:1/16:0), Cer (18:1/18:0), Cer (18:1/24:1)), and decreased eGFR.
  • Cer (18:1/16:0) showed the strongest correlation with baseline SYNTAX score (bSS) and highest predictive accuracy for complex CAD.
  • Combined CKD and elevated Cer (18:1/16:0) significantly increased complex CAD risk (OR = 4.40).
  • Renal impairment mediated a significant portion of ceramide's atherogenic effects.

Conclusions:

  • Ceramide-renal synergy exacerbates coronary atherosclerosis.
  • Integrated biomarker profiling of ceramides and renal function is recommended for risk stratification.
  • Dual-targeted therapies addressing both ceramides and renal dysfunction may be beneficial for managing atherosclerosis.
Abstract

Keywords:
CeramideCoronary artery diseaseMediationRenal impairmentSYNTAX score

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