Abstract: SA-PO305
Circulating Proteins Associated with Apoptosis Processes and Fast Progression to ESKD in Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: Clinical Pathology, Diagnostic and Treatment Advances
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 702 Diabetic Kidney Disease: Clinical
Authors
- Ihara, Katsuhito, Joslin Diabetes Center, Boston, Massachusetts, United States
- Satake, Eiichiro, Joslin Diabetes Center, Boston, Massachusetts, United States
- Md Dom, Zaipul, Joslin Diabetes Center, Boston, Massachusetts, United States
- Krolewski, Bozena, Joslin Diabetes Center, Boston, Massachusetts, United States
- Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
Background
Many circulating proteins associated with risk of end-stage kidney disease (ESKD) have been identified in diabetic kidney disease (DKD). However, the biological pathways and disease processes they represent are unknown.
Methods
This global-untargeted proteomic study used the Olink platform to measure the concentrations of 455 proteins in plasma specimens obtained at baseline examination of 405 individuals with DKD. We used logistic regression to examine the associations between these proteins and the development of ESKD. This investigation consisted of two nested case-control studies from the Joslin Kidney Study. One study included individuals with T1D, and the other included individuals with T2D who were at risk of developing ESKD during a 7-15 year follow-up period. For pathway enrichment analysis of the differentially expressed proteins, we applied the Database for Annotation, Visualization, and Integrated Discovery (DAVID 6.8). Additionally, to assess whether the models based on apoptosis proteins captured all the predictive information for ESKD, we applied least absolute shrinkage and selection operator (LASSO) logistic regression.
Results
We identified 46 circulating proteins with elevated concentrations that were associated with the development of ESKD (n=149) during a 7-15 year follow-up period (p value <10-5 for all 46 proteins). Twenty of these proteins were enriched in the apoptosis/TNF receptors signaling pathways. A small subset of 5 proteins out of the 46 (KIM-1, TNF-R27, IL-1RT1, TNF-R11A, and TNF-R6B in descending order of predictive ability), summarized as the apoptosis score, along with clinical variables, accurately predicted the risk of progression to ESKD.
Conclusion
Elevated levels of numerous circulating proteins, indicating apoptotic processes and TNF receptors signaling pathways, preceded fast progression to ESKD. These proteins may be used to predict and monitor the disease process leading to ESKD in DKD.
Funding
- NIDDK Support – Novo Nordisk Foundation