Abstract: PO0732
Circulating Fibroblast Growth Factor 20 (FGF-20) as a Novel Protein Protective Against Progression to ESKD in Diabetes
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
- Md Dom, Zaipul I, Joslin Diabetes Center, Boston, Massachusetts, United States
- Satake, Eiichiro, Joslin Diabetes Center, Boston, Massachusetts, United States
- Kobayashi, Hiroki, Joslin Diabetes Center, Boston, Massachusetts, United States
- Krolewski, Bozena, Joslin Diabetes Center, Boston, Massachusetts, United States
- Wilson, Jonathan M., Eli Lilly and Company, Indianapolis, Indiana, United States
- Duffin, Kevin L., Eli Lilly and Company, Indianapolis, Indiana, United States
- Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
Background
Growing evidence from animal, cellular and targeted biomarker studies supports an involvement of fibroblast growth factor (FGF) family members (FGF23, FGF21) in diabetic kidney disease (DKD) progression. However, the majority of the studies were cross-sectional and performed in a targeted manner focusing on individual proteins. Therefore, we aimed to comprehensively evaluate the profiles of circulating FGF proteins in progressive DKD leading to end-stage kidney disease (ESKD) in individuals with diabetes.
Methods
This was a prospective cohort study of individuals with type 1 (n=214) and type 2 (n=144) diabetes, persistent proteinuria and CKD Stage 3 followed for progression to ESKD within 10 years. Measurement of circulating FGF proteins (n=17) were performed in baseline plasma samples using aptamer-based (SOMAscan) proteomic profiling.
Results
One hundred eight (50%) and 35 (24%) individuals with T1D and T2D, respectively, developed ESKD within 10 years. Six out of 17 FGF proteins were protective against progression to ESKD in the univariable Cox regression model. The strongest protection was observed for FGF20 (HR (95% CI): 0.68 (0.59, 0.79), p=7.0x10-7). The cumulative 10-year risk of ESKD was about 2 times lower in individuals with high versus low levels of FGF20. Three proteins remained significant after further adjustment by clinical covariates, however, only the protective effect of FGF20 was confirmed in a third cohort of T1D individuals (n=294) with early DKD (CKD Stage 1 and 2); (OR (95% CI): 0.48 (0.37, 0.61), p=6.1x10-9). Interestingly, non-diabetic parents of T1D children with ESKD or Proteinuria had lower FGF20 concentrations than those parents with T1D children without kidney complications.
Conclusion
This study identified circulating FGF20 as protective against progression to ESKD in three independent cohorts of individuals with T1D and T2D and varying stages of DKD. The protective effect was independent from the clinical legacy measures of DKD. Identification of proteins that protect individuals from ESKD may be useful targets for the development of therapeutics for preventing or delaying the onset of ESKD.
Funding
- NIDDK Support