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Abstract: TH-PO177

Serum Sphingolipids as Indicators of ESRD Risk in Diabetic Patients

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • Kharkar, Vismaya Jui, The University of Utah School of Medicine, Salt Lake City, Utah, United States
  • Pezzolesi, Marcus G., The University of Utah Department of Human Genetics, Salt Lake City, Utah, United States

Group or Team Name

  • Pezzolesi Lab.
Background

Chronic kidney disease (CKD) is a complication of diabetes that affects one-third of diabetic patients; 15% of CKD patients with diabetes develop end-stage renal disease (ESRD). Underlying genetic, environmental, and biological factors contribute significantly to CKD risk.
Sphingolipids are a class of lipids that have been associated with increased insulin resistance and hepatic steatosis. Through analysis of longitudinal data from participants in Chronic Renal Insufficiency Cohort (CRIC) study and newly generated lipidomic data, this project investigates the potential use of longitudinal serum sphingolipid measurements as an indicator for risk of progression to ESRD.

Methods

We analyzed ESRD outcomes in participants of CRIC with type II diabetes and CKD (n = 1054). We performed targeted lipidomics measuring 55 sphingolipids in patient serum samples from their fifth CRIC visit. Data from this visit served as the baseline for evaluating time to progression to ESRD and change in serum sphingolipids over time. Additionally, patients’ health variables available through the CRIC dataset were investigated for correlation with all sphingolipids at baseline for a larger cohort of 1618 patients with diabetes and CKD. Each variable was analyzed for correlation with each sphingolipid using a standardized linear regression model; variables were then grouped using hierarchical clustering according to both p-value and adjusted R-squared value.

Results

At baseline, 506 patients had early stage CKD (CKD stages 1-3) and 546 patients had late stage CKD (CKD stages 4-5). 257 of 1054 patients developed ESRD in the range of 517 to 5048 days after the first CRIC visit, with a mean of 2619 days. Seven of 55 serum sphingolipids were significantly (p < 0.05) associated with time to ESRD; none explained greater than 0.01% of variability. Additionally, we identified 3 clusters of patient health variables that were significantly (p < 0.05) associated with the same sphingolipids and with each other . These clustered health variables included lipid measurements, indicators of kidney function, and quality of life evaluation.

Conclusion

Our analysis indicates that serum sphingolipids measured at baseline are correlated with progression to ESRD. As we continue our analysis, we further investigate the relationship between average sphingolipid measurements over time and rate of progression through CKD stages to ESRD.

Funding

  • NIDDK Support