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Abstract: PO0985

Associations of Circulating Angiopoietins with Renal Function Decline and Progression to ESKD in CKD Stage 3 Patients with Diabetes

Session Information

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
  • O'Neil, Kristina V., Joslin Diabetes Center, Boston, Massachusetts, United States
  • Kobayashi, Hiroki, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Ihara, Katsuhito, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Skupien, Jan, Jagiellonian University Medical College, Krakow, Poland
  • Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
Background

The literature on plasma angiopoietins (Ang) levels in patients with diabetes and CKD Stage 3 is sparse. The data pertaining the association of Ang with progression of renal decline and development of ESKD is similarly limited. This study aimed to investigate relationships between circulating angiopoietins with risk of progressive renal decline and ESKD in diabetic patients with already existing moderate renal impairment.

Methods

We prospectively studied 214 T1D patients and 144 T2D patients over a follow-up period of 7-15 years to determine eGFR slope and ascertain time of onset of ESKD. Serial measurements of serum creatinine were used to estimate the rate of eGFR decline. Fast decliners were defined as eGFR loss ≥ 3.0 ml/min/year. We quantified Ang1, Ang2 and Tie-2 present on the SOMAscan proteomic platform in baseline plasma samples in diabetics as well as in 79 non-diabetics. We examined the association of plasma levels of each Ang and the rate of fast renal decline using logistic regression models.

Results

There were 143 and 75 fast decliners in T1D and T2D (Median eGFR slope -6.2 ml/min/year in both cohorts), respectively. In regression models adjusted for baseline eGFR, HbA1c, ACR and type of diabetes, Ang1 (OR (95% CI): 0.77 (0.61, 0.96)) or Ang1/Ang2 ratio (OR: 0.74 (0.59, 0.94)) was significantly associated with protection against fast renal decline. Neither Ang2 (OR: 1.21 (0.96, 1.51)) nor Tie-2 (OR: 1.12 (0.89, 1.39)) was associated with the rate of fast renal decline. Patients with Ang1 levels above median and Ang2 below median had very low cumulative incidence of ESKD of 30%. The lowest baseline Ang1 levels were observed in non-diabetic controls (Median (25th, 75th percentiles): 757 (641, 1189)) and the highest values were observed in slow decliners (Median: 1565 (1093, 2522)), while fast-decliner levels (Median: 1248 (934, 1916)) fell between the two other sub-groups.

Conclusion

Elevated Ang1 levels or the ratio of Ang1/Ang2 had a protective effect against fast renal decline and progression to ESKD. As such, Ang1 and Ang2 may be useful targets for preventing or delaying the onset of renal function decline and ESKD in diabetes.

Funding

  • NIDDK Support