Kidney Week

Abstract: PO0736

Long Non-Coding RNA Profiles and Declining Kidney Function in Patients with Diabetes and CKD

Session Information

• Diabetic Kidney Disease: Clinical
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Satake, Eiichiro, Joslin Diabetes Center, Boston, Massachusetts, United States

Eiichiro Satake, PhD

• Kobayashi, Hiroki, Joslin Diabetes Center, Boston, Massachusetts, United States

Hiroki Kobayashi,

• Md Dom, Zaipul I, Joslin Diabetes Center, Boston, Massachusetts, United States

Zaipul I Md Dom,

• O'Neil, Kristina V., Joslin Diabetes Center, Boston, Massachusetts, United States

Kristina V. O'Neil,

• Krolewski, Bozena, Joslin Diabetes Center, Boston, Massachusetts, United States

Bozena Krolewski,

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

Marcus G. Pezzolesi,

• Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States

Andrzej S. Krolewski,

Background

Long non-coding RNAs (lncRNAs) are endogenous molecules that are involved in gene regulation and play important roles in the pathogenesis of various renal diseases, including diabetic kidney disease (DKD). lncRNA signatures associated with DKD, however, have not been fully established. The objective of this study was to determine the whole blood lncRNA signature that is associated with increased risk of DKD progression.

Methods

Eighty-eight lncRNAs that were previously reported to be related to DKD were measured by quantitative PCR (qPCR) in RNA from whole blood (PAXgene RNA tubes) from 22 patients with type 1 diabetes and chronic kidney disease (12 of whom progressed to ESKD during 7-10 years of follow-up). GAPDH was used for sample normalization. We assessed declining kidney function as eGFR slope (ml/min/1.73m²/year).

Results

Seventy-two of the 88 lncRNAs were detectable in more than half of the samples included in this study (n>11). Using Pearson’s test, eGFR slope was found to be significantly correlated with lncRNAs H19 (r=-0.56, P=0.0073) and CRNDE (r=-0.42, P<0.05). H19 and CRNDE were not correlated with HbA1c (r=0.22, P=0.32 and r=-0.15, P=0.52 respectively), suggesting that these lncRNAs are associated with progression of DKD mediated by distinct pathway(s) independent of hyperglycemic condition.

Conclusion

We investigated plasma lncRNA profiles associated with declining kidney function in patients with diabetes. Although we need to confirm the results in an independent validation panel, our findings suggest that H19 and CRNDE are associated with declining kidney function and have potential to serve as circulating biomarkers for progression of DKD.

Funding

• Commercial Support – Novo Nordisk