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Chronic Kidney Disease, Circulating Ceramides, and Coronary Microvascular Dysfunction: Insights from the CRUISE-MET

Qiang Chen^1,2, Xuexi Li^1,2, Yingying Xie^1,2

¹China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Cardiorenal Medicine

|April 30, 2026

Insights

Ceramides, particularly Cer(18:1/16:0), partially mediate the link between chronic kidney disease (CKD) and coronary microvascular dysfunction (CMD). This suggests sphingolipid metabolism plays a role in cardiorenal disease.

Area of Science:

Cardiovascular Medicine
Nephrology
Biochemistry

Background:

Coronary microvascular dysfunction (CMD) is independently associated with ceramides and chronic kidney disease (CKD).
The combined impact of ceramides and CKD on CMD is not well-established.
Investigating this interplay is crucial for understanding cardiorenal pathophysiology.

Purpose of the Study:

To examine the combined association of ceramides and CKD with CMD.
To investigate the mediating role of ceramides in the relationship between CKD and CMD.
To identify key factors, including ceramides and CKD, associated with CMD.

Main Methods:

Cross-sectional analysis of 794 coronary artery disease patients from the CRUISE-MET trial.
Assessment of microvascular resistance using angiography-derived microcirculatory resistance (AMR).
Ceramide profiling and CKD classification based on eGFR and UACR; statistical mediation analysis.

Main Results:

CKD patients had higher AMR and CMD prevalence.
Three ceramide species, especially Cer(18:1/16:0), correlated positively with AMR.
Cer(18:1/16:0) and CKD were top correlates of CMD, with Cer(18:1/16:0) showing significant predictive performance.
Concurrent CKD and elevated Cer(18:1/16:0) significantly increased CMD odds (OR=3.74).

Conclusions:

Ceramides, particularly Cer(18:1/16:0), partially mediate the association between CKD and CMD.
Sphingolipid metabolism is implicated in cardiorenal pathophysiology.
These findings may inform novel therapeutic strategies for cardiorenal disease.

Read full analysis

Abstract

Introduction:

Ceramides and chronic kidney disease (CKD) independently associate with coronary microvascular dysfunction (CMD), but their combined association remains unestablished, warranting investigation.

Methods:

This cross-sectional analysis included coronary artery disease (CAD) patients from the CRUISE-MET trial (NCT06383208) who underwent coronary angiography and ceramide profiling measurement. The microvascular resistance was assessed in all patients using the angiography-derived microcirculatory resistance (AMR). CKD was classified based on both estimated glomerular filtration rate and urine albumin-to-creatinine ratio. The combined associations and statistical mediation of ceramides and renal dysfunction on CMD was examined, with sensitivity analyses to ensure the robustness.

Results:

In this analysis of 794 CAD patients, CKD patients demonstrated significantly higher AMR values (2.56 ± 0.51 vs. 2.46 ± 0.48, p = 0.003) and CMD prevalence (57.1% vs. 41.7%, p < 0.001). Three ceramide species - Cer(18:1/16:0), Cer(18:1/18:0), and Cer(18:1/24:1) - showed strong positive correlations with AMR (all p < 0.05). LASSO regression identified 14 factors associated with CMD, with E/e', CKD, and Cer(18:1/16:0) emerging as top correlates. Cer(18:1/16:0) demonstrated superior predictive performance (area under the curve [AUC] = 0.609, 95% CI: 0.570-0.648, p < 0.001), with its addition to baseline models significantly improving reclassification (δAUC = 0.03, p = 0.010; cNRI>0 = 0.23, p < 0.001; integrated discrimination improvement = 0.03, p < 0.001). Notably, patients with concurrent CKD and elevated Cer(18:1/16:0) exhibited significantly higher odds of CMD (OR = 3.74, 95% CI: 2.39-5.84). Statistical mediation analysis suggested that Cer(18:1/16:0) mediated 13.8% of the association between CKD and CMD.

Conclusion:

Ceramides, particularly Cer(18:1/16:0), partially mediated the statistical association between CKD and CMD. These findings highlight the potential role of sphingolipid metabolism in cardiorenal pathophysiology.

Keywords:

Angiography-derived microcirculatory resistance Ceramide Chronic kidney disease Coronary artery disease Coronary microvascular dysfunction

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