Abstract: TH-OR48
Ephrin Signaling and the Development of Early Progressive Kidney Function Decline
Session Information
- Diabetic Kidney Disease - Clinical: Novel Insights into Precision Medicine
October 24, 2024 | Location: Room 33, Convention Center
Abstract Time: 04:50 PM - 05:00 PM
Category: Diabetic Kidney Disease
- 702 Diabetic Kidney Disease: Clinical
Authors
- Md Dom, Zaipul, Joslin Diabetes Center, Boston, Massachusetts, United States
- Satake, Eiichiro, Joslin Diabetes Center, Boston, Massachusetts, United States
- Tye, Sok Cin, Joslin Diabetes Center, Boston, Massachusetts, United States
- Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
Background
We were the first to report a novel role of Ephrin family members in the progression of kidney failure in diabetes (Satake et al. JASN 2021). However, whether higher Ephrin protein levels are associated with or causally related to the development of early progressive kidney function decline (PKFD) is unknown.
Methods
We assessed EPHA2 and EFNA4 protein levels using Joslin Olink proteomics platform among participants in the Joslin Kidney Study (JKS, n=1,269) and the Chronic Renal Insufficiency Cohort study (CRIC, n=1,170). We compared baseline levels of EPHA2 and EFNA4 across albuminuria categories with T1D and T2D and evaluated their associations with kidney outcomes (kidney failure, eGFR slope and eGFR-based outcomes).
Results
EPHA2 and EFNA4 levels increased progressively from non-diabetics to normoalbuminuria (NA), microalbuminuria (MA), and proteinuria (PT) in both cohorts (Figure 1A). Significant variations were observed between T1D and T2D, and across all albuminuria categories with the highest levels observed in PT. T2D individuals consistently had higher EPHA2 and EFNA4 levels compared to T1D. Both proteins showed significant negative correlations with eGFR, particularly pronounced in MA and PT. In the CRIC cohort, EPHA2 and EFNA4 had significant positive correlations with UACR across all albuminuria categories. Baseline EPHA2 levels were significantly associated with kidney failure in models adjusted for HbA1c, eGFR and UACR (Figure 1B, JKS PT: HR [95%CI] =1.52 [1.21-1.91], p=0.00035, c-index=0.797); CRIC NA: HR [95%CI] =2.61 [1.05-6.19], p=0.029, c-index=0.789, adjusted for competing mortality).
Conclusion
Our findings suggest that elevated levels of circulating EPHA2 and EFNA4 play a role in the initiation of early PKFD and can be used as predictors for the development of early PKFD.
Funding
- NIDDK Support