Endostatin, chronic kidney disease (CKD) and anemia among older people: a secondary analysis of the screening for CKD among older people across Europe (SCOPE) study

Anemia is a common and debilitating complication of chronic kidney disease (CKD), but its pathogenesis remains incompletely understood. Endostatin, an anti-angiogenic peptide that is elevated in CKD, may impair erythropoiesis through vascular dysfunction. We investigated the relationship between circulating endostatin and both prevalent and incident anemia in older adults, as well as whether kidney function modified this association. We analyzed data from 2,008 participants aged ≥ 75 years enrolled in the Screening for CKD among Older People across Europe (SCOPE) prospective cohort. Cross-sectional associations between standardized log-transformed endostatin and hemoglobin levels or prevalent anemia were assessed using linear and logistic regression, respectively. Dose-response relationships were explored across endostatin tertiles. Longitudinal analyses included 1,394 non-anemic individuals followed for two years; incident anemia was assessed using Fine-Gray competing risk models, with death treated as a competing event. Models were progressively adjusted for demographics, comorbidities, kidney function, iron status, medications, and baseline hemoglobin. Sensitivity analyses included Winsorization and subgroup interaction testing. At baseline, 405 participants (20.2%) had anemia. Higher endostatin levels were independently associated with lower hemoglobin levels (β -0.21, 95% CI -0.28 to -0.14) and higher odds of prevalent anemia (OR, 95% CI: 1.38, 1.18–1.62). During follow-up, 159 of 1,394 participants (11.4%) developed anemia; higher endostatin levels predicted incident anemia (sHR, 95% CI: 1.40, 1.17–1.69), with more than a twofold higher risk in the highest tertile. Associations were stronger among patients with CKD and were significantly modified by eGFR, advanced age, and the absence of diabetes. These findings suggest that vascular dysfunction may contribute to anemia in older adults and identify endostatin as a potential biomarker of the risk of anemia, particularly among individuals with CKD.