FRAILTY, CARDIOVASCULAR FUNCTION AND RISK OF FALLING AMONGST PATIENTS WITH STAGE 5 CHRONIC KIDNEY DISEASE ON HAEMODIALYSIS
This PhD thesis explores the risk of falling of stage 5 chronic kidney disease (CKD-5) patients receiving haemodialysis (HD) therapy. Previous research has suggested that multiple risk factors such as older age, comorbidities, polypharmacy, and frailty contribute primarily to the increased risk of falling in this clinical population. However, HD patients are also characterised by severe cardiovascular disease burden that often manifests with symptoms of orthostatic intolerance, impaired blood pressure control and syncope, all of which may be implicated in the aetiology of falling. The aim of this thesis was to address important research questions, such as: Are frailty and its physical function/activity components associated with falling in CKD-5 patients on HD? Are baroreflex function and the cardiovascular responses to orthostasis also associated with falling? What is the relative importance of frailty and cardiovascular function as potential exercise-modifiable risk factors for falls in this patient group? A prospective observational study involving 76 prevalent HD patients (61.1±14 years) confirmed previous observations that CKD-5 patients on HD are at higher risk of falls compared to the non-uraemic population, as 37.7% of research participants experienced at least one fall during a 12-month follow-up, and the incidence of falls recorded was 1.16 falls/person-year. Although participants classified as fallers did not appear to differ from non-fallers in single physical function measures such as timed-up and go (TUG), 5 repetitions chair sit to stands (CSTS-5), or muscle strength, frailty and lower postural balance were associated with increased odds of falling. In addition, baroreflex function indices reflecting frequency of baroreflex activation, as well as the blood pressure response to a five-minute 60° head-up tilt test (HUT-60°) were associated with increased odds of falling and a greater number of falls. More importantly, we showed that modelling the risk of falling by adding a cardiovascular function variable to a frailty-only model improved significantly the prediction of number of falls experienced by CKD-5 patients on HD. Overall, this PhD thesis revealed that cardiovascular mechanisms implicated in the short-term regulation of blood pressure showed a greater relative importance than frailty in predicting falls in the study participants. These findings challenge the current assumption that frailty is the primary factor involved in the aetiology of falls in CKD-5 patients on HD. The clinical implications of this novel observation are also discussed from a preventive and rehabilitative perspective. Key words: Stage 5 chronic kidney disease, haemodialysis, falls, frailty, cardiovascular function.