Exercise and Lifestyle Intervention in patients with Chronic Kidney Disease

Chronic kidney disease (CKD) is associated with increased risk of death from cardiovascular disease far in excess of the general population. The prevalence of traditional risk factors is high but does not fully account for the high event rate. Effective strategies are lacking to minimise risk factors, and management of patients with CKD is complex and multi-factorial. Furthermore, studies investigating the effect of exercise training and lifestyle intervention are lacking and the ability to generalise findings due to patient selection is limited in patients with CKD stage 3 and 4. Overall this thesis aims to evaluate the effect of exercise training and lifestyle intervention on cardiovascular disease risk in patients with CKD. In addition this thesis will also demonstrate the predictors of exercise capacity in CKD patients and evaluate the relationship between renal function, exercise capacity and left ventricular filling pressures. This research program will also report on the pre-screening process used in this PhD program and compare its effectiveness in accurately estimating risk. Chapter one provides an introduction to the research program. Chapter two will evaluate the current incidence, prevalence and impact of cardiovascular disease on CKD and review the current evidence for exercise training in patients with stage 3 and 4 CKD. A systematic review was conducted, and discusses in detail the current evidence on the effect of exercise training in the CKD population. The quality of the majority of studies was low with most being non-randomised, non-controlled trials. These studies have excluded participants who have significant co-morbidities or pre-existing coronary heart disease and some do not report inclusion or exclusion criteria. This limits the ability to generalise the findings from these studies to the CKD population. Despite combination exercise training being the preferred training modality, only two studies have used this form of training. Chapter three provides a comprehensive description of the methods used throughout the study and the justification of choice of outcomes. Chapter three also includes a detailed description of the exercise and lifestyle intervention. Chapter four assesses the contribution of myocardial and vascular parameters in addition to traditional cardiovascular risk factors to cardiorespiratory fitness in patients with CKD. This study found that both myocardial function (left ventricular pressure [E/e’]) and vascular structure (carotid intima-media thickness and aortic pulse wave velocity) independently predict reduced cardiorespiratory fitness in patients with CKD. This study also found that CKD patients who achieve their age predicted VO2 peak have significantly better vascular and arterial health. Chapter five is the first study to examine pre-exercise screening methods in patients with CKD. This chapter identifies that pre-exercise screening is highly relevant in this population, as we identified that even in asymptomatic patients there was a high incidence of silent ischaemia. This chapter also recommends that additional screening methods should be investigated before best practice guidelines can be made to exercise physiologist and nephrologists. Chapter six compares diastolic function at rest and in response to maximal exercise in patients with CKD matched with patients with a similar level of cardiovascular disease risk as measured by the Framingham risk equation. We found that whilst both groups had similar diastolic function at rest and in response to exercise, CKD patients had a significantly lower exercise capacity. Interestingly we found that systolic tissue velocity was reduced in the CKD patients, but ejection fraction was normal. This thesis has confirmed the prominent presence of diastolic dysfunction in CKD patients and establishes a relationship between diastolic dysfunction and cardiorespiratory fitness. Chapter seven and eight assess the effect of the 12 month exercise and lifestyle intervention. In chapter seven we explain that there was a significant effect of the intervention on improving exercise capacity and body composition. Improvements in exercise capacity were independently predicted by allocation to the intervention. Chapter eight discusses the effect of the intervention on myocardial, arterial and vascular parameters. We found that the intervention significantly improved diastolic function and that this was independently predicted by allocation to the intervention. Chapter nine summarises the major findings and conclusions of the thesis. The exercise training intervention presented in this thesis is the largest to date in patients with CKD and found extremely favourable outcomes in terms of improved exercise capacity, body composition and myocardial function as a consequence of the intervention. The findings from this intervention add much needed robust data to the field