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

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 thathigher 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 - NIH NCOR-KUH, 1U2CDK140919-01