Assessing Gait in Chronic Kidney Disease - A look into an unexplored field

Abstract

Chronic Kidney Disease (CKD) is of a degenerative nature that affects about 10% of the world’s population and is 12th in the rankings of leading causes of death worldwide. CKD is classified into five stages by severity. Patients at stage 5 need a renal replacement therapy (RRT) in the form of a transplantation or dialysis. The reduced filtration capacity of the kidney negatively impacts the homeostasis and the function of several organ systems already at stage 3. In particular, these patients lose muscle mass, which leads to sarcopenia, and they also have a higher rate of cognitive impairment. Instrumented gait analysis has been for many years a part of clinical practice in many fields, such as geriatrics, where it is used for assessing fall risk, neuromuscular function, dementia diagnosis and the efficacy of a therapeutic intervention. The control of gait requires both energy (muscle strength, cardiovascular capacity) and cognitive resources. A reduced muscle strength leads to a lower gait speed and a shorter stride length, cognitive impairment instead to a higher variability of spatio-temporal parameters that are identifiable in the gait cycle. The CKD population has many pathologies that can negatively impact the quality of walking. An instrumented gait analysis may therefore be useful for an early diagnosis of these pathologies and would allow researchers to understand preclinical and prodromal disease stages of these pathologies. This would provide the basis for novel targeted prevention treatments. This thesis will exemplify the use of wearable technology to assess gait in the clinic, thus outlining how gait analysis can support the clinical diagnosis of CKD-related pathologies. This includes evidence of unique signatures of gait which can aid the identification of cognitive impairment. Furthermore, the potential and key recommendations for the future implementation of gait in the diagnostic toolkit for CKD is explored. In a first step, existing knowledge about gait in CKD patients was systematically gathered. The results of this systematic review revealed a dearth of knowledge about gait in this clinical population. Therefore, in a cross-sectional study we collected spatio-temporal and variability data of gait in 45 patients split into 5 disease severity groups. The results confirm not only the linear relationship between decrease in gait speed and increase in renal function impairment, as described in the systematic review, but also the worsening of variability parameters in relation to the disease progression. The analysis of the clinical parameters collected in the study – that show a reduction of muscle strength and a worsening performance in some neuropsychological tests – reinforce the validity of the data collected through the instrumented gait analysis. The cross-sectional study warranted performance of a longitudinal study in which CKD individuals were followed over time. In a series of longitudinal clinical studies, the transitional phase, lasting from some months prior to the start of haemodialysis (HD) to two years of the replacement therapy, was analysed. The goal of these investigations was to determine whether the start of the HD coincides with an acceleration of the frailty process in the recruited patients, as suggested in many publications. The results show that the patients are already frail in the pre-dialysis phase, and that neither clinical nor gait parameters indicate a worsening of the health condition once the RRT has started. The high rate of frailty patients in the HD population, therefore, does not seem to be directly caused by elements of the therapy, but can be attributed to some factors already present in the predialysis stage. The low number of participants, their older age, and the fact that they have been under strict medical control by a nephrologist for a number of years, could have influenced the outcome of the studies, which in any case are declared as being purely explorative. However, the results underscore the potential of gait analysis in CKD patients that so far has been neglected both in research and clinical settings. In conclusion, our studies have shown that CKD negatively affects health status in the middle stage of disease progression, and that this is reflected in an altered gait pattern. Consequently, the fact that people on HD are particularly frail is not directly caused by factors related to the RRT, but seems to be part of the frailty process that starts many years before, when kidney function begins to deteriorate. The introduction of a standardized protocol for instrumented gait analysis to assess possible root causes for frailty in CKD patients in the early disease stages, together with the collection of clinical data, could make it possible to obtain clinically relevant information for explaining the relation between CKD and concomitant comorbidities, and to better study eligibility criteria for a kidney transplantation. In addition, in the light of the high rate of cognitive disorders, it would be interesting to investigate the benefits of cognitive-motor training in this population, as the results with this kind of activity have been promising in several other fields.