Functional and Cognitive Impairment, Frailty, and Adverse Health Outcomes in Older Patients Reaching ESRD-A Systematic Review

Background and objectives Older patients reaching ESRD have a higher risk of adverse health outcomes. We aimed to determine the association of functional and cognitive impairment and frailty with adverse health outcomes in patients reaching ESRD. Understanding these associations could ultimately lead to prediction models to guide tailored treatment decisions or preventive interventions. Design, setting, participants, & measurements We searched MEDLINE, Embase, Web of Science, CENTRAL, CINAHL, PsycINFO, and COCHRANE for original studies published until February 8, 2016 reporting on the association of functional or cognitive impairment or frailty with adverse health outcome after follow-up in patients reaching ESRD either with or without RRT. Results Of 7451 identified citations, we included 30 articles that reported on 35 associations. Mean age was >60 years old in 73% of the studies, and geriatric conditions were highly prevalent. Twenty-four studies (80%) reported on functional impairment, seven (23%) reported on cognitive impairment, and four (13%) reported on frailty. Mortality was the main outcome measure in 29 studies (97%), and one study assessed functional status trajectory. In 34 of 35 (97%) associations reported, functional or cognitive impairment or frailty was significantly and independently associated with adverse health outcomes. The majority of studies (83%) were conducted in selected patient populations, mainly patients on incident dialysis. Conclusions Functional and cognitive impairment and frailty in patients reaching ESRD are highly prevalent and strongly and independently associated with adverse health outcomes, and they may, therefore, be useful for risk stratification. More research into their prognostic value is needed

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 >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