Sleep Disturbance in Patients with Advanced Chronic Kidney Disease or End-Stage Renal Disease.pdf (8.09 MB)

Sleep Disturbance in Patients with Advanced Chronic Kidney Disease or End-Stage Renal Disease

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posted on 05.08.2020 by Claire Kennedy
Patients with advanced chronic kidney disease (CKD) or end-stage renal
disease (ESRD) have a large burden of symptoms, with sleep
disturbance, restless legs syndrome and fatigue among the most
prevalent (1). These sleep-related symptoms are considered an absolute
priority for both treatment and research by patients and their caregivers
(2). Despite this, clinicians consistently underestimate and overlook these
symptoms in clinical encounters (3). The impact of RRT modality choice
on such symptoms is not well defined and is poorly communicated to
patients choosing between modalities. In fact, communication regarding
the impact of modality choice is so poor that patients consistently report
feeling excluded entirely from ‘shared decision-making’ (4). It is critical
that physicans consider the impact of RRT modality on all aspects of
patient care, including sleep, engage patients in this major decision, and
communicate in outcomes that patients understand and value (such as
symptoms and quality of life).
Disturbed sleep has a major negative impact on health-related quality of
life, mood, and neurocognitive function. There is a growing body of
evidence suggesting that sleep disturbance in general, and some of the
specific sleep disorders in particular, are independent cardiovascular risk
factors (5). The American Heart Association called for promotion of
healthy sleep along with other risk factor modifications in their 2019
scientific statement (6). Patients with advanced CKD or ESRD are already
at high cardiovascular risk, and any modifiable element to this risk should
be aggressively managed.
The impact of initiating a particular RRT modality or changing RRT
modality on sleep-related symptoms is not well understood, particularly in
the case of the nocturnal therapies, where alarms and anxiety may
counteract any positve effects of improved uraemia and extracellular fluid
volume control. My published, peer-reviewed, systematic review aimed to
assess the impact of a change in RRT modality on sleep quality in
patients with ESRD (7). Sixteen heterogeneous studies, with a combined
total of 670 patients and 191 controls, were included. Meta-analysis of the
sixteen studies favoured increased intensity RRT (either intensive
hemodialysis (HD), automated peritoneal dialysis (APD) or transplant)
over conventional RRT (conventional HD or continuous ambulatory
peritoneal dialysis (CAPD)) in terms of overall sleep quality, with statistical
significance. Restless legs syndrome (RLS) and sleep apnoea also
improved in the majority of patients following a switch to increased
intensity RRT.
This cohort study assessed sleep quality in sixty patients (unselected for
sleep disturbance) with advanced CKD or ESRD. There was a high
prevalence of self-reported poor sleep quality (54%), RLS, (44%) and
excessive daytime sleepiness (22%). Polysomnography (PSG) and
actigraphy studies identified marked sleep fragmentation and distorted
sleep architecture, with longer time than usual spent in the lighter stages
of sleep, and shorter time than usual spent in the deeper, restorative
stages of sleep. Sleep apnoea and abnormal periodic limb movements
(PLMs) were also highly prevalent (44% and 47% respectively). Marked
benefits in terms of sleep quality, health related quality of life (HRQoL)
and sleep apnoea were demonstrated post-transplant in the subgroup that
were transplanted. Many parameters of subjective and objective sleep
quality improved after either initiating dialysis from chronic kidney disease
(CKD) or optimisation dialysis in those already on some form of dialysis.
There was a high prevalence (44%, n=14) of sleep apnoea in the 32
patients that underwent baseline PSG, with older age as an independent
risk factor. Screening tools (such as the Epworth Sleepiness Scale) and
actigraphy did not accurately predict the diagnosis or obviate the need for
PSG for the diagnosis. 70% of patients with an abnormal apnoeahypopnoea
index (AHI) had subjective and / or objective improvement
with initiation of continuous positive airways pressure (CPAP) or
optimisation of RRT. As there is emerging evidence that sleep apnoea is
an independent cardiovascular risk factor in ESRD, the concept of treating
sleep apnoea and potentially improving the cardiovascular risk profile is
an appealing one (8).

RLS and abnormal PLMs were also prevalent (45% and 47%
respectively). Increased age was, again, an independent risk factor.
Actigraphy did not predict an abnormal PLM index but was useful in
selected cases. 73% of patients with an abnormal PLM index had
subjective and / or objective improvement with pharmacologic therapy or
optimisation of RRT. As there is emerging evidence that PLMs are
associated with nocturnal hypertension and increased cardiovascular risk
in ESRD, the concept of treating them and modifying this risk is, again,
appealing (9).
With regard to screening for sleep disturbance, the individual
questionnaires performed poorly in terms of predicting their specific
outcome of interest in this study cohort. However, the Pittsburgh Sleep
Quality Index (PSQI) proved useful in identifying those patients who had
sleep disturbance in general (rather than a specific problem). Paired
actigraphy and PSG analyses showed good agreement for sleep
efficiency and time spent awake after sleep onset. The PSQI and wrist
actigraphy may, therefore, help to triage patients for PSG assessment in
jurisdictions with limited PSG access. There were no safety issues with
the 55 unattended home PSG studies and seventy actigraphy studies,
including those performed during nocturnal dialysis (PD or HD).
To conclude, sleep disorders are highly prevalent, easily and safely
studied with unattended home PSG and eminently modifiable in stable
outpatients with advanced CKD or ESRD. Given that the sleep disorders
have such a negative impact on clinical outcomes in these patients,
identification and management of sleep disorders should be a priority in
Nephrology clinics. With ongoing dissemination of these research
findings, we hope to highlight the prevalence of sleep disorders in this
population, guide appropriate investigations, facilitate discussions
regarding modality choice, encourage patients and doctors to intensify
dialysis, and ultimately contribute to improved management of sleep
disorders and patient outcomes in patients with advanced CKD or ESRD.


First Supervisor

Professor RW Costello

Second Supervisor

Professor PJ Conlon


A thesis submitted for the degree of Doctor of Medicine from the Royal College of Surgeons in Ireland in 2019.

Published Citation

Kennedy C. Sleep Disturbance in Patients with Advanced Chronic Kidney Disease or End-Stage Renal Disease. [MD Thesis]. Dublin: Royal College of Surgeons in Ireland; 2019.

Degree Name

Doctor of Medicine (MD)

Date of award



  • Doctor of Medicine (MD)