Chronic kidney disease is common, affecting up to 25% of the elderly population. CKD is associated with both increased morbidity and mortality. The mainstay of treatment is blood pressure control. Whilst hypertension guidelines exist, there is significant concern amongst many practicing clinicians about their applicability to the older person. This concern is primarily due to falls risk. Falls are a significant problem in this age-group with a serious impact on those who fall, their families and the wider health economy. Whilst falls risk is multi-factoral, medication load (especially antihypertensives) is both significant and modifiable. The aim of this thesis is therefore to explore the risk-benefit relationship between blood pressure control, antihypertensive therapy and falls in older people with CKD. This was performed via an interlinked collection of clinical trials, culminating in an interventional drug trial. Traditionally such trials have focused on the effect of a drug (or combination of therapeutic agents), whereas we examined the effect of the therapeutic strategy of blood pressure control itself, as well as the effects of therapy beyond blood pressure itself. Our key results are: • Impairment of autonomic nervous system function can predict mortality in CKD, independent of other significant predictors. • Autonomic function is highly modifiable even in patients established on dialysis, and that these can be affected by factors such as PD fluid composition. • Body composition is highly variable over time in CKD. This is seen both in those on dialysis, and in pre-dialysis patients. • Antihypertensive therapy is associated with an acute reduction in circulating endotoxaemia. Whilst the long-term effect of this alteration is unknown, endotoxaemia is known to be associated with poor outcomes in many disease populations similar to CKD. • Antihypertensive therapy causes significant acute improvement in many markers of cardiovascular health in a cohort of older people with CKD (and non-CKD controls). Other effects of goal-directed AHT are also described, including changes to bone mineral biochemistry. • Antihypertensive therapy causes sustained improvement in many markers of cardiovascular health over a 12 month period in older people. Non-cardiovascular changes are also seen, some sustained from the original acute AHT use, whilst others regress towards baseline values. Falls remain relatively rare, and appear non-cardiovascular in origin. Cardiovascular disease in CKD is complex, and BP control remains a key component of its management. The data presented herein suggest that older people with CKD may benefit from aggressive risk reduction with AHT, just as young people do, and it is not appropriate to significantly modify this approach as a response to increased age alone.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:594588 |
| Date | January 2013 |
| Creators | John, Stephen G. |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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