Roel Bijkerk1,2, Marije H Kallenberg1,3, Laurien E Zijlstra4, Bernard M van den Berg1,2, Jeroen de Bresser5, Sebastiaan Hammer6, Esther E Bron7, Hakim Achterberg7, Mark A van Buchem5, Noeleen C Berkhout-Byrne1, Willem Jan W Bos1,8, Diana van Heemst3, Ton J Rabelink1,2, Anton Jan van Zonneveld1,2, Marjolijn van Buren1,9, Simon Mooijaart3,10. 1. Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands. 2. Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands. 3. Department of Internal Medicine (Gerontology and Geriatrics), Leiden University Medical Center, Leiden, The Netherlands. 4. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. 5. Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. 6. Department of Radiology, Haga Hospital, The Hague, The Netherlands. 7. Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. 8. Department of Internal Medicine, St Antonius Hospital, Nieuwegein, The Netherlands. 9. Department of Nephrology, Haga Hospital, The Hague, The Netherlands. 10. Institute of Evidence-Based Medicine in Old Age, Leiden, The Netherlands.
Abstract
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.
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.
Authors: Qiao Zhao; Sabine J L Nooren; Laurien E Zijlstra; Jos J M Westenberg; Lucia J M Kroft; J Wouter Jukema; Noeleen C Berkhout-Byrne; Ton J Rabelink; Anton Jan van Zonneveld; Marjolijn van Buren; Simon P Mooijaart; Roel Bijkerk Journal: Noncoding RNA Date: 2022-01-10
Authors: Barend W Florijn; Roel Bijkerk; Nyika D Kruyt; Anton Jan van Zonneveld; Marieke J H Wermer Journal: Int J Mol Sci Date: 2021-11-02 Impact factor: 5.923