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Publications

Journal Article Epublish

PubMed: 42533353 DOI: 10.1186/s12967-026-08601-4

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.

J Transl Med 24(1)

Authors: Andrea Corsonello, Luca Soraci, Johan Ärnlöv, Axel C Carlsson, Tobias Rudholm Feldreich, Anders Larsson, Regina Roller-Wirnsberger, Gerhard Wirnsberger, Francesco Mattace-Raso, Lisanne Tap, Francesc Formiga, Rafael Moreno-González, Tomasz Kostka, Agnieszka Guligowska, Ronit Ben-Romano, Itshak Melzer, Christian Weingart, Robert Kob, Cornel C Sieber, Lucia Muglia, Fabrizia Lattanzio

Affiliations

  • Italian National Research Center on Aging (IRCCS INRCA), Ancona, Cosenza, Fermo, Italy.
  • Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende (CS), Italy.
  • Italian National Research Center on Aging (IRCCS INRCA), Ancona, Cosenza, Fermo, Italy.
  • School of Health and Welfare, Dalarna University, Falun, Sweden.
  • Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden.
  • Academic Primary Health Care Centre, Stockholm Region, Stockholm, Sweden.
  • Section of Clinical Chemistry, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Department of Internal Medicine, Medical University of Graz, Graz, Austria.
  • Section of Geriatric Medicine, Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Geriatric Unit, Internal Medicine Department, Bellvitge University Hospital, IDIBELL - L'Hospitalet de Llobregat, Barcelona, Spain.
  • Department of Geriatrics, Healthy Ageing Research Centre, Medical University of Lodz, Lodz, Poland.
  • Department of Physical Therapy, The Recanati School for Community Health Professions at the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
  • Department of General Internal Medicine and Geriatrics, Krankenhaus Barmherzige Brüder Regensburg, Regensburg, Germany.
  • Institute for Biomedicine of Aging, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nurnberg, Germany.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

MeSH

Kidney Diseases, Hemoglobins, Anemia, Biomedical Research, Kidney, Endostatins