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Crowley, Lisa E. (2016) Cardiac ischaemic stress in the haemodialysis patient. PhD thesis, University of Nottingham.

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Abstract

Haemodialysis patients experience elevated levels of cardiovascular morbidity and mortality that has a profound effect on not only their survival and quality of life but also increases the already high social and economic cost of dialysis. It is increasingly appreciated that the circulatory stress caused by dialysis is a significant contributing factor and helps to accelerate the end organ damage this group of patients is known to experience. In particular the cumulative ischaemic insult suffered by the heart during haemodialysis sessions has been suggested as one of the principal drivers of heart failure and sudden cardiac death – the two principal causes of death in this population.

The importance of dialysis induced haemodynamic instability was reinforced as we explored the relationship between cardiac function and the measure of intra-dialytic hypotension most clearly associated with mortality (a blood pressure below 90mmHg) and found that the severity of dialysis induced cardiac injury was experienced across the whole range of dialysis induced hypotension. A nadir blood pressure below 90mmHg was strongly associated with established reduction in systolic contractile function.

We then tested two separate interventions designed to mitigate dialysis-induced injury. The first was Remote Ischaemic Preconditioning, a technique that in pre-clinical models and numerous small clinical studies protects against the effect of the ischaemia-reperfusion injury. We found that a single application of RIPC significantly reduces dialysis induced cardiac injury for up to 28 days. The second intervention was the stepwise reduction of dialysate sodium to reduce intra-dialytic fluid accumulation and the need for aggressive ultrafiltration. We found this to be well tolerated and an effective way to reduce inter-dialytic weight gain. This intervention did not have any adverse cardiac consequences and may have resulted in a modest improvement in cardiac tolerability while still being delivered within the context of a conventional 4-hour haemodialysis treatment.

Finally, to investigate if transplantation is capable of reversing any of the factors predisposing dialysis patients to increased cardiovascular events, we chose to investigate one of the risk factors that contributes to the abnormalities of the vasculature and leave patients vulnerable to dialysis induced cardiac injury. We measured the deposition of advanced glycation end-products (via the method of skin autofluorescence) in patients who had undergone renal transplantation and compared this to existing cohorts of dialysis and chronic kidney disease patients. We found that following transplantation these markers of metabolic stress regressed to levels comparable to those seen in chronic kidney disease and much lower than seen in dialysis. This finding may suggest that the dialysis procedure itself is responsible for a great deal of metabolic stress and helps to accelerate the process by which the vasculature becomes stiff and non-compliant.

In conclusion, we tested two interventions that showed potential to reduce the cardiac stress dialysis patients are subject to. Remote ischaemic preconditioning directly reduces the severity of cardiac injury and the stepwise reduction of dialysate sodium decreases inter-dialytic fluid gains and produces a modest improvement in cardiac tolerability. We also confirmed that transplantation reverses advanced glycation end-product deposition, one of the key non-traditional risk factors for cardiovascular disease in dialysis patients, giving us further insight into the ways in which transplantation improves cardiovascular outcome.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	McIntyre, C.W.
Keywords:	Hemodialysis, Cardiovascular disease, Cardiac stress, Remote ischaemic preconditioning, Dialysate sodium reduction
Subjects:	W Medicine and related subjects (NLM Classification) > WJ Urogenital system
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID:	33527
Depositing User:	Crowley, Lisa
Date Deposited:	15 Aug 2016 09:00
Last Modified:	16 Dec 2017 11:22
URI:	https://eprints.nottingham.ac.uk/id/eprint/33527

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