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Abstract: FR-PO437

Circulating MicroRNA Profiles and Risk of ESRD in Patients with Diabetes and CKD: An RNA-Sequencing Based Study

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Satake, Eiichiro, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, United States
  • Pezzolesi, Marcus G., University of Utah, Salt Lake City, Utah, United States
  • Simeone, Christopher, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Md Dom, Zaipul I, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, United States
  • Kobayashi, Hiroki, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, United States
  • Smiles, Adam, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Niewczas, Monika A., Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, United States
  • Krolewski, Andrzej S., Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, United States
Background

MicroRNAs (miRNAs) are endogenous, short non-coding RNA molecules that are involved in gene regulation and play important roles in the pathogenesis of various diseases including diabetic kidney disease (DKD). However, miRNA signatures associated with DKD has not been fully established.

Methods

Using High Throughput Genomics (HTG) edge sequence platform, the expression of 2,083 mature miRNAs were examined in baseline plasma specimens from 239 patients with type 1 diabetes (T1D) and CKD stages 3 & 4 to find miRNAs associated with progression to ESRD during 7-15 years of follow-up. The findings in T1D were validated using the same technology in the replication panel of 136 patients with type 2 diabetes (T2D) and the same CKD stages.

Results

Cox proportional hazard model analysis revealed that 15 miRNAs were strongly associated with renal function decline and time to ESRD in both T1D and T2D. Using Spearman’s rank test, 3 candidate miRNAs were significantly associated with declining renal function after adjusting for age, sex, type of diabetes, duration of diabetes, HbA1c, eGFR and ACR (p<0.05). In pathway analysis, 6 KEGG pathways (Endocytosis, FoxO signaling, mTOR signaling, Neurotrophin signaling, Rap1 signaling and Ras signaling) were significantly enriched by genes targeted by all 3 miRNAs (P<0.01).

Conclusion

We investigated plasma miRNA profiles associated with ESRD in patients with diabetes using RNA-sequencing based platform. Our results suggest that these miRNAs are associated with declining renal function in patients with diabetes and have potential to serve as circulating biomarkers, and possibly therapeutic targets for DKD.

Funding

  • NIDDK Support