Ageing Res Rev. 2026 Sep 6:103355. doi: 10.1016/j.arr.2026.103355. Online ahead of print.
ABSTRACT
Chronic kidney disease (CKD) is increasingly recognized as a model of accelerated biological aging, characterized by premature cardiovascular disease and frailty. Although frailty has become a cornerstone of gero-nephrology, current frailty models primarily emphasize physical performance and functional decline, providing limited insight into the vascular mechanisms underlying biological vulnerability. Conversely, vascular aging is traditionally framed within cardiovascular medicine, with little integration into contemporary frailty research, limiting our understanding of how vascular dysfunction contributes to biological aging in CKD. In this review, we propose vascular frailty as a unifying framework that bridges geroscience, nephrology, and vascular medicine. We summarize the mechanisms through which CKD accelerates vascular aging and discuss vascular reserve and vascular resilience as key biological concepts linking vascular aging to systemic frailty. This underlies our claim that vascular frailty could be a multidimensional phenotype integrating structural vascular remodeling, functional vascular impairment, and conventional frailty assessment. Emerging approaches for operationalizing vascular frailty through vascular imaging, physiological assessment, and biomarker profiling are also highlighted. Rather than representing another frailty subtype, vascular frailty provides a conceptual framework linking vascular aging, loss of vascular reserve, and systemic vulnerability in CKD. Emerging evidence supports the feasibility of integrating structural and functional vascular measures with conventional frailty assessment, although its incremental prognostic and clinical value remain to be established. Further longitudinal and interventional studies are needed to determine whether vascular frailty can contribute to risk stratification, individualized management, and strategies aimed at preserving vascular resilience in CKD and other aging-related conditions.
PMID:42702293 | DOI:10.1016/j.arr.2026.103355