Kidney Week

Abstract: FR-PO1165

Plasma Ceramides and Risk of Cardiovascular Events in CKD

Session Information

• CKD: Kidney Function and Extrarenal Complications
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Moghaddam, Farahnaz Akrami, University of Utah Health, Salt Lake City, Utah, United States

Farahnaz Akrami Moghaddam, MSc

• Pezzolesi, Marcus G., University of Utah Health, Salt Lake City, Utah, United States

Marcus G. Pezzolesi, PhD, MPH

• Sarwal, Amara, University of Utah Health, Salt Lake City, Utah, United States

Amara Sarwal, MD

• Boucher, Robert E., University of Utah Health, Salt Lake City, Utah, United States

Robert E. Boucher

• Takyi, Augustine, University of Utah Health, Salt Lake City, Utah, United States

Augustine Takyi

• Hartsell, Sydney Elizabeth, University of Utah Health, Salt Lake City, Utah, United States

Sydney Elizabeth Hartsell, MD, MPH

• Chakravartula, Akhil Ramanujam, University of Utah Health, Salt Lake City, Utah, United States

Akhil Ramanujam Chakravartula, MD, MBBS

• Katkam, Niharika, University of Utah Health, Salt Lake City, Utah, United States

Niharika Katkam, MSc

• Wei, Guo, University of Utah Health, Salt Lake City, Utah, United States

Guo Wei, MS

• Shen, Jincheng, University of Utah Health, Salt Lake City, Utah, United States

Jincheng Shen, MS, PhD

• Summers, Scott, University of Utah Health, Salt Lake City, Utah, United States

Scott Summers, PhD

• Beddhu, Srinivasan, University of Utah Health, Salt Lake City, Utah, United States

Srinivasan Beddhu, MD

Background

Ceramide (CER) accumulation in tissues is implicated in platelet dysfunction, inflammation, insulin resistance, and atherosclerosis. As altered plasma CER predicts CV events, a Cardiovascular Event Risk Test (CERT)1 score based on plasma CER has been developed in the general population. It is unknown whether plasma CER and CERT1 scores predict CV events in CKD.

Methods

We measured plasma CER with targeted lipidomics in year 1 visit samples of 1054 Chronic Renal Insufficiency Cohort (CRIC) participants with T2D. Based on plasma levels of CER 16:0, 18:0, 24:1 and their ratios to CER 24:0, CERT1 scores were calculated as 2 points for concentrations or ratios in the 4^th quartile and 1 point for concentrations or ratios in the 3rd quartile of the reference population. In separate multivariate Cox regression models adjusted for variables listed in Figure, we related individual CER, ratios, and CERT1 scores with a composite of adjudicated MI, HF, stroke or CV death.

Results

The mean age was 61 ± 9 years, 57% were male, 49% were African American, baseline eGFR was 46 ± 13 ml/min/1.73 m² and mean CERT1 score was 4.4 ± 3.4. There were 454 CV events/8654 patient years of follow-up. While CER 16:0, 18:0, and 24:1 were not associated with CV events (Figure), CER 24:0 had a lower risk and the ratios of CER 16:0, 18:0, and 24:1 to CER 24:0 were significantly associated with higher CV risk. Each standard deviation increase in CERT1 score (3.4 points) was associated with CV events(HR 1.16, 95% CI 1.04 to 1.30).


.

Conclusion

CER 24:0 and the ratios of CER 16:0, 18:0, 24:1 to CER 24:0 predict CV events in CKD independent of BMI, serum lipids and statin use. CERT1 score but not all of its components were associated with CV events in CKD suggesting that calibration and discrimination of CERT1 score in CKD could be improved with a CKD specific score.

Funding

• NIDDK Support