Abstract: TH-PO0349
Profiles of Circulating MicroRNAs Associated with the Development of ESKD in Diabetes
Session Information
- Diabetic Kidney Disease: From Early Biomarkers to Novel Therapeutic Targets
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 702 Diabetic Kidney Disease: Clinical
Authors
- Satake, Eiichiro, Joslin Diabetes Center, Boston, Massachusetts, United States
- Krolewski, Bozena, Joslin Diabetes Center, Boston, Massachusetts, United States
- Wilson, Jonathan Matthew, Eli Lilly and Company, Indianapolis, Indiana, United States
- Wilson, Parker C., University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
- Apostadero, Aaron, Joslin Diabetes Center, Boston, Massachusetts, United States
- Kobayashi, Hiroki, Joslin Diabetes Center, Boston, Massachusetts, United States
- Md Dom, Zaipul, Joslin Diabetes Center, Boston, Massachusetts, United States
- Hoon, Dave, Saint John's Cancer Institute, Santa Monica, California, United States
- Duffin, Kevin L., Eli Lilly and Company, Indianapolis, Indiana, United States
- Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
Background
MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression post-transcriptionally, and play key roles in kidney disease pathogenesis. We previously identified 17 circulating cell-free miRNAs (cfmiRNAs) associated with end-stage kidney disease (ESKD) risk in patients with diabetes and stage 3–4 chronic kidney disease (CKD) (Satake et al, JASN 2021). In this study, we expanded the analysis to earlier CKD stages (1–2) and evaluated potential sources of these cfmiRNAs.
Methods
Using the RNA extraction-free HTG EdgeSeq platform, we profiled 2,083 mature miRNAs in baseline bleeds cell-free plasma from 331 patients with type 1 or type 2 diabetes and preserved kidney function (eGFR >60 ml/min). We combined these results with previously published data from 375 patients with CKD stage 3-4. Associations between baseline cfmiRNA concentration and 10-year ESKD risk were analyzed using Cox proportional hazard models adjusted for clinical covariates. Expression of ESKD-associated cfmiRNAs in white blood cells (WBC) was evaluated using Paxgene RNA, and tissue expression patterns (ex., kidney) were assessed based on previous reports.
Results
Multivariate Cox models identified 22 plasma cfmiRNAs significantly associated with ESKD risk in both early and late CKD stages. These included 10 risk cfmiRNAs (high concentration associated with higher risk) and 12 protective cfmiRNAs (higher concentration associated with lower risk). Of these, 13 overlapped with our prior panel, while 9 were newly identified. Risk miRNAs had low expression in WBCs compared to cell-free plasma, while protective miRNAs showed moderate to high WBC expression. According to the previous report (Bustos et al., Clin Chem 2024), risk miRNAs were minimally expressed in the healthy kidney, whereas protective miRNAs were moderately to highly expressed.
Conclusion
We confirmed and extended our previous findings by demonstrating that plasma cfmiRNA profiles associated with ESKD risk are consistent across early and late CKD stages. The organ/tissue sources of risk and protective cfmiRNAs in circulation are dramatically different. More research is needed to evaluate their potential as plasma biomarkers and therapeutic targets for diabetic kidney disease.
Funding
- NIDDK Support