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

Background The prevalence of end-stage renal disease (ESRD) is increasing worldwide, with the majority of new ESRD cases diagnosed in patients aged >60 years. 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 (ADMA), and a selection of eight circulating angiogenic miRNAs with SVD and cognitive impairment in older patients reaching ESRD that did not initiate renal replacement therapy yet (n = 129; mean age 75.3 years; mean eGFR 16.4 mL/min). We assessed brain MRI changes of SVD (white matter hyperintensity volume, microbleeds and presence of lacunes) and measures of cognition in domains of memory, psychomotor speed and executive function, comprised in a neuropsychological test battery. Results Older patients reaching ESRD showed an unfavorable angiogenic profile, as indicated by aberrant levels of Ang-2 and five angiogenic miRNAs (miR-27a, miR-126, miR-132, miR-223, miR-326), compared to healthy persons and patients with diabetic nephropathy. Moreover, Ang-2 associated with SVD and with the domains of psychomotor speed and executive function, while miR-223 and miR-29a 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 give insight into the underlying (vascular) pathophysiology.