Circulating angiopoietin-2 and angiogenic microRNAs associate with cerebral small vessel disease and cognitive decline in older patients reaching end-stage renal disease

Roel Bijkerk*, Marije H. Kallenberg, Laurien E. Zijlstra, Bernard M. Van Den Berg, Jeroen De Bresser, Sebastiaan Hammer, Esther E. Bron, Hakim Achterberg, Mark A. Van Buchem, Noeleen C. Berkhout-Byrne, Willem Jan W. Bos, Diana Van Heemst, Ton J. Rabelink, Anton Jan Van Zonneveld, Marjolijn Van Buren, Simon Mooijaart

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background: The prevalence of end-stage renal disease (ESRD) is increasing worldwide, with the majority of new ESRD cases diagnosed in patients >60 years of age. These older patients are at increased risk for impaired cognitive functioning, potentially through cerebral small vessel disease (SVD). Novel markers of vascular integrity may be of clinical value for identifying patients at high risk for cognitive impairment. Methods: We aimed to associate the levels of angiopoietin-2 (Ang-2), asymmetric dimethylarginine and a selection of eight circulating angiogenic microRNAs (miRNAs) with SVD and cognitive impairment in older patients reaching ESRD that did not yet initiate renal replacement therapy (n = 129; mean age 75.3 years, mean eGFR 16.4 mL/min). We assessed brain magnetic resonance imaging changes of SVD (white matter hyperintensity volume, microbleeds and the presence of lacunes) and measures of cognition in domains of memory, psychomotor speed and executive function in a neuropsychological test battery. Results: Older patients reaching ESRD showed an unfavourable angiogenic profile, as indicated by aberrant levels of Ang-2 and five angiogenic miRNAs (miR-27a, miR-126, miR-132, miR-223 and miR-326), compared with healthy persons and patients with diabetic nephropathy. Moreover, Ang-2 was associated with SVD and with the domains of psychomotor speed and executive function, while miR-223 and miR-29a were associated with memory function. Conclusions: Taken together, these novel angiogenic markers might serve to identify older patients with ESRD at risk of cognitive decline, as well as provide insights into the underlying (vascular) pathophysiology.

Original languageEnglish
Pages (from-to)498-506
Number of pages9
JournalNephrology Dialysis Transplantation
Issue number3
Publication statusPublished - 1 Mar 2022

Bibliographical note

R.B. is supported by a grant from the Dutch Kidney Foundation (16OKG16) and R.B. and A.J.V.Z. are supported by a grant
from the European Foundation for the Study of Diabetes. Additional support was provided to A.J.V.Z by the Dutch Heart
Foundation in the context of the CVON consortium RECONNECT and to M.J.P.V.O., M.A.V.B., E.E.B. and H.C.A. in the context of the CVON consortium Heart Brain
Connection (CVON 2018-28 and 2012-06).

Publisher Copyright:
© 2020 The Author(s). Published by Oxford University Press on behalf of the ERA.


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