Kidney Lifestyle Research Program Program 2024 funded by the Stoneygate Trust

Open to UK applicants only

Supervisors

• Daniel March dsm12@le.ac.uk
• Dr Matthew Graham-Brown mgb23@le.ac.uk
• Prof James Burton jb343@le.ac.uk 

Background

Individuals with end-stage kidney disease (ESKD) have a significantly increased risk of cardiovascular disease, which is the leading cause of death in this population. Despite improvements in the care and management of these individuals, strategies to mitigate this enhanced cardiovascular risk have had little impact due to the non-traditional risk factors of chronic inflammation, uraemia, anaemia, renal bone-disease and haemodialysis-induced myocardial stunning associated with individuals receiving haemodialysis, (1-3). One unrecognised factor (possibly due to different clinical presentation (4)) that may contribute to this enhanced cardiovascular risk is the presence of sleep disordered breathing (SDB) (5). SDB is characterised by periodic interruptions in breathing during sleep with consequent adverse effects on the cardiovascular system mediated through chemical, autonomic, mechanical and inflammatory pathways. The main subgroups of SDB include obstructive sleep apnoea (OSA), central sleep apnoea (CSA), and mixed sleep apnoea (6). Sleep apnoea has been associated with cardiovascular and all-cause mortality in CKD (7-10). 
Prevalence of sleep apnoea is believed to increase as chronic kidney disease (CKD) progresses (12), and has been reported to be highest in those with ESKD (12). In recent unpublished data (13) investigating the prevalence of sleep apnoea in people receiving dialysis it was reported that the prevalence of sleep apnoea is 59%, with the majority being obstructive in nature. Despite this high prevalence, sleep apnoea in the haemodialysis population is poorly detected by nephrologists (14), which is thought to results in many people with sleep apnoea not being treated for this condition.
The gold standard method of detecting sleep apnoea is through polysomnography (sleep study), however this requires a visit to the sleep clinic which can be costly, time-consuming, and is not readily available for the people who need it most. Screening questionnaires may be a more efficient way of detecting sleep apnoea in people with CKD. Within the United Kingdom, the National Institute for Health and Care Excellence (NICE) currently recommends the STOP-Bang questionnaire. However, it is thought that this questionnaire may not accurately rule out the presence of sleep apnoea in the ESKD population (15). The poor utility of this questionnaire may due to the fact that some of the components used to score the STOP-Bang such as body mass index and neck circumference may not be strongly associated with sleep apnoea in the ESKD population (16). Another method of screening for sleep apnoea is through the use of sleep monitor devices (such as oximeters) which measure a number of physiological responses, these have previously been shown to provide an estimate of sleep apnoea compared to polysomnography. It is unknown how the STOP-Bang questionnaire compares against data from oximeters in the haemodialysis population.  
In both the general and ESKD population, continuous positive airway pressure (CPAP) is the treatment of choice for clinically significant moderate to severe OSA. This would normally be initiated through referral to the clinical sleep service and a subsequent diagnosis of OSA. However, there is little evidence from the dialysis population that this treatment is effective, with only one small study previously assessing its effectiveness. Moreover, somewhat surprisingly a further trial  (17) showed that adaptive servo-ventilation therapy for people with a reduced ejection fraction and central sleep apnoea increased all cause and cardiovascular mortality. Given the increased cardiovascular risk in individuals with ESKD (and the presence of central sleep apnoea) it is imperative that future studies investigate the efficacy and safety of CPAP for the treatment of apnoea in the dialysis population. 
This doctoral studentship will have the overall aim of assessing the prevalence of sleep apnoea (along with associated factors), in addition to assessing the safety and effectiveness of treatments in the dialysis population using a range of methodologies.  The project plan and methodology will be refined and finalised when the successful candidate has begun their studentship, however the following outline is currently proposed:


- Establish the prevalence of sleep apnoea in the haemodialysis (within the Leicester Renal Network) using the STOP-Bang questionnaire and oximetry.
- Understand which dialysis specific factors are associated with the presence of haemodialysis 
- Follow up people receiving dialysis who have been referred to the sleep clinic at University Hospitals of Leicester; and identify associated factors
- Assess the safety of continuous positive airway pressure (CPAP) on cardiovascular function in people receiving haemodialysis 
-  
The successful candidate will become embedded within the Leicester Kidney Partnership which sits within the Department of Cardiovascular Sciences. The group is a vibrant multidisciplinary research group, which aims to help patients living with kidney disease achieve the best possible health and wellbeing. Training and support in a wide variety of areas is available where necessary to support this studentship. 

References

1. Graham-Brown MP, Patel A, Stensel D, March DS, Marsh A-M, McAdam J, et al. Imaging of myocardial fibrosis in patients with end-stage renal disease: current limitations and future possibilities. BioMed Research International. 2017;2017.
2. Kendrick J, Chonchol MB. Nontraditional risk factors for cardiovascular disease in patients with chronic kidney disease. Nature clinical practice Nephrology. 2008;4(12):672-81.
3. Burton JO, Jefferies HJ, Selby NM, McIntyre CW. Hemodialysis-induced cardiac injury: determinants and associated outcomes. Clinical journal of the American Society of Nephrology: CJASN. 2009;4(5):914.
4. Weisbord SD, Fried LF, Mor MK, Resnick AL, Unruh ML, Palevsky PM, et al. Renal provider recognition of symptoms in patients on maintenance hemodialysis. Clinical Journal of the American Society of Nephrology. 2007;2(5):960-7.
5. Partinen M, Jamieson A, Guilleminault C. Long-term outcome for obstructive sleep apnea syndrome patients: mortality. Chest. 1988;94(6):1200-4.
6. Abuyassin B, Sharma K, Ayas NT, Laher I. Obstructive sleep apnea and kidney disease: a potential bidirectional relationship? Journal of Clinical Sleep Medicine. 2015;11(8):915-24.
7. Yang XH, Zhang BL, Gu YH, Zhan XL, Guo LL, Jin HM. Association of sleep disorders, chronic pain, and fatigue with survival in patients with chronic kidney disease: a meta-analysis of clinical trials. Sleep Medicine. 2018;51:59-65.
8. Xu J, Yoon IY, Chin HJ. The effect of sleep apnea on all-cause mortality in nondialyzed chronic kidney disease patients. Sleep medicine. 2016;27:32-8.
9. Jhamb M, Ran X, Abdalla H, Roumelioti M-E, Hou S, Davis H, et al. Association of sleep apnea with mortality in patients with advanced kidney disease. Clinical Journal of the American Society of Nephrology. 2020;15(2):182-90.
10. Tang SC, Lam B, Yao TJ, Leung WS, Chu CM, Ho YW, et al. Sleep apnea is a novel risk predictor of cardiovascular morbidity and death in patients receiving peritoneal dialysis. Kidney international. 2010;77(11):1031-8.
11. Kerns ES, Kim ED, Meoni LA, Sozio SM, Jaar BG, Estrella MM, et al. Obstructive sleep apnea increases sudden cardiac death in incident hemodialysis patients. American journal of nephrology. 2018;48(2):147-56.
12. Nicholl DD, Ahmed SB, Loewen AH, Hemmelgarn BR, Sola DY, Beecroft JM, et al. Declining kidney function increases the prevalence of sleep apnea and nocturnal hypoxia. Chest. 2012;141(6):1422-30.
13. Daniel S March LB, Kelly Barber, Ffion Curtis, Patrick J Mowles, Nina Morris, Ellesha A Smith, Sonny Vargeson, James O Burton. Prevalence and characteristics of treatments for sleep disordered breathing in people receiving dialysis: A Scoping Review Under Review. 2025.
14. Burkhalter DA, Cartellá A, Cozzo D, Ogna A, Forni Ogna V. Obstructive sleep apnea in the hemodialysis population: are clinicians putting existing scientific evidence into practice? Frontiers in Nephrology. 2024;4:1394990.
15. Nicholl DD, Ahmed SB, Loewen AH, Hemmelgarn BR, Sola DY, Beecroft JM, et al. Diagnostic value of screening instruments for identifying obstructive sleep apnea in kidney failure. Journal of Clinical Sleep Medicine. 2013;9(1):31-8.
16. Huang H-C, Walters G, Talaulikar G, Figurski D, Carroll A, Hurwitz M, et al. Sleep apnea prevalence in chronic kidney disease-association with total body water and symptoms. BMC nephrology. 2017;18:1-9.
17. Cowie MR, Woehrle H, Wegscheider K, Angermann C, d’Ortho M-P, Erdmann E, et al. Adaptive servo-ventilation for central sleep apnea in systolic heart failure. New England Journal of Medicine. 2015;373(12):1095-105.