Association of symptoms of insomnia and sleep parameters among kidney transplant recipients
Introduction
Several studies suggest that 50–80% of patients with end-stage kidney disease (ESKD) may have sleep-related problems, including insomnia [1], [2], [3], [4], restless legs syndrome [5], [6], [7], periodic limb movements in sleep [2], [5], [6], [7] and obstructive sleep apnea [8], [9], [10]. Successful kidney transplantation might alleviate some sleep problems [3], [11], but the prevalence of poor sleep remains remarkably high among these patients: 52.5% among kidney transplant (kTx) recipients were poor sleeper in a cohort study [12]. We previously showed the percentage of kTx recipients who had at least one insomnia complaint was nearly 1.5 times higher compared to the general population [3].
Insomnia and poor sleep are frequent complaints in kTx recipients and they are associated with fatigue [13], depression [3], [4], pain [4], post-traumatic stress-symptoms [4] and lower quality of life [3], [12], [14]. Surprisingly, there is almost a complete lack of information regarding objectively measured sleep parameters in kTx recipients. Altough there are a few published articles that report polysomnographic assessment of sleep in kTx recipients [15], [16], [17], [18], [19] most reports focus on obstructive sleep apnea and do not analyze sleep structure in details [16], [17], [18], [19].
Insomnia disorder is characterized by difficulty falling asleep, difficulty staying asleep or poor sleep quality, and it leads to impaired daytime functioning, tiredness, fatigue and sleepiness according to the International Classification of Sleep Disorders III and Diagnostic and Statistical Manual of Mental Disorders V criteria [20], [21]. These complaints can be of multi-factorial origin among kTx recipients. Anxiety, fear of rejection, deteriorating graft function, altered metabolism of sleep-regulatory mediators, ongoing subclinical inflammation, the presence of other comorbid conditions, immunosuppressant (IS) or other medications and hospitalization may all influence a preexisting sleep disorder or contribute to de novo emergence of sleep problems [22], [23].
Diagnosis of insomnia in CKD is similar to the diagnosis among the general population and it is based on clinical interview [23]. The assessment of polysomnography (PSG) is required only when a comorbid sleep-disorder is suspected. However, studies using PSG and detailed EEG analysis contributed important information about the pathophysiology of insomnia among non-kidney disease patients and helped to develop better therapies to improve the subjective symptoms. Patients with insomnia disorder often have longer sleep onset latency (SOL) [24], [25], lower total sleep time (TST) [24], [25], [26], [27], dysregulated sleep homeostasis (less slow wave sleep [SWS] or delta activity) [24], [26], [28], [29] or higher wake time after sleep onset (WASO) [24], [25], [27], [30]. Moreover, increased wake-like (beta) EEG activity during sleep is also characteristic for patients with insomnia [27], [31], [32].
The association of subjective insomnia complaints with objectively assessed sleep architecture and EEG activity (microstructure) have not been investigated before among kTx recipients. However, gaining insight into the objective structure of sleep behind the subjective symptoms might help to treat patients with insomnia more properly among this patients population. Thus, in this study we hypothesized that, similarly to patients with insomnia but no kidney disease, insomnia symptoms are associated with altered sleep macro- and microstructure paramateres (longer SOL, shorter TST, less SWS and delta activity, higher WASO and beta activity).
Section snippets
Sample of patients and data collection
Data for this analysis are obtained from the “SLeep disorders Evaluation in Patients after kidney Transplantation (SLEPT) study” [15], [19], [33], [34], [35], [36], [37], [38], [39], [40]. Potentially eligible patients were selected from all prevalent adult transplant recipients (“total clinic population”; n = 1214) who were regularly followed at a single outpatient academic transplant center, the kidney transplant clinic of the Dept. of Transplantation and Surgery at Semmelweis University,
Results
The demographic and laboratory parameters, comorbid conditions and transplantation related data of the “kTx PSG sample” are presented in Table 1. Descriptive data of sleep macrostructure parameters are presented in Table 2.
Discussion
This is the first study analyzing detailed sleep architecture and sleep EEG activity associated with insomnia symptoms in kTx recipients. Our main finding is that the severity of insomnia symptoms is associated with higher amount of SWS and higher beta power during REM sleep.
While there is a growing literature about the importance of subjective sleep quality among kTx recipients [3], [4], [12], [57], only limited information has been published about the objectively measured sleep
Acknowledgements
The authors thank patients and staff of the Dept. of Transplantation and Surgery and the Sleep Laboratory at the 1st Dept. of Internal Medicine, Semmelweis University, Budapest, Hungary. The analysis was performed at the Inst. of Behavioural Sciences, Semmelweis University, Budapest, Hungary. RB received personal fees from Pharma Nord Hungary – unrelated to this research. MZM received a Grant from NIH and had a position at Merck Advisory Board – both were unrelated to this research. The other
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