Kidney Week

Abstract: FR-PO1163

Association of Serum Angiopoeitin-2 with Kidney Function Decline Among Participants in the Multiethnic Study of Atherosclerosis (MESA) Cohort

Session Information

• CKD: Screening, Diagnosis, Serum and Urine Biomarkers, and Scoring Indices
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Assefa, Mahlet, University of Washington, Seattle, Washington, United States

Mahlet Assefa, MD

• Zelnick, Leila R., University of Washington, Seattle, Washington, United States

Leila R. Zelnick, PhD

• Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States

Bryan R. Kestenbaum, MD, MS

• Liles, Wayne Conrad, University of Washington, Seattle, Washington, United States

Wayne Conrad Liles, MD, PhD

• Leary, Peter J., University of Washington, Seattle, Washington, United States

Peter J. Leary, MD, PhD

• Bansal, Nisha, University of Washington, Seattle, Washington, United States

Nisha Bansal, MD, FASN

• Bhatraju, Pavan K., University of Washington, Seattle, Washington, United States

Pavan K. Bhatraju, MD, MS

Background

Circulating levels of angiopoietin-1 (ang-1) and angiopoietin-2 (ang-2) reflect endothelial activation and dysfunction. While higher ang-2 levels have been associated with chronic kidney disease (CKD) progression, it is unknown if ang-2 levels are associated with development of eGFR decline in healthy persons. We hypothesized that elevated ang-2 levels will be associated with increased risk of developing ≥30% eGFR decline.

Methods

We analyzed data from MESA, a cohort study of >6,000 adults without cardiovascular disease enrolled between 2000-2002. Ang-2 levels were measured in baseline serum for 1,406 participants with enrollment and at least one follow up eGFR. We used Cox regression to estimate the association of ang-2 with the primary outcome of an incident ≥ 30% eGFR decline, controlling for age, sex, race, body mass index, socioeconomic status, smoking, site, baseline eGFR and hypertension (HTN). Statistical significance was set at two-tailed p-value of <0.05.

Results

Among 1,406 participants, mean age was 61 years, mean baseline eGFR was 79 mL/min/1.73 m², 49% were male, 12% had diabetes and 12% had CKD at study enrollment. The median ang-2 level was 4,804 (IQR 3712-6341) pg/mL and 196 participants developed the primary outcome. Baseline risk factors associated with higher ang-2 included participants identifying as Black, current smokers and those diagnosed with diabetes, CKD and HTN. After adjustment, a doubling in ang-2 was associated with 1.42 times higher risk of the primary outcome (95% CI 1.10-1.83, p = 0.006). The association between ang-2 and the primary outcome seemed linear (Figure 1).

Conclusion

These results show that higher serum ang-2 levels are associated with greater risk of significant decline in renal function in a healthy, community population. Given the strong biological rationale for the importance of endothelial instability in the loss of kidney function, further investigation of the role of ang-2 is warranted.

Funding

• Other NIH Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025kzyk4ftp