Dreams disrupted: a comprehensive review of sleep disorders in chronic kidney disease

Georges Kosmadakis; Clémence Deville; Aura Nécoara; Julien Baudenon; Ioana Enache; Fatima El Kanouni; Joseph El Hajal

doi:10.23876/j.krcp.25.080

Kidney Res Clin Pract > Epub ahead of print

Kosmadakis, Deville, Nécoara, Baudenon, Enache, Kanouni, and Hajal: Dreams disrupted: a comprehensive review of sleep disorders in chronic kidney disease

Review Article

Kidney Research and Clinical Practice 2025;j.krcp.25.080.

Published online: July 30, 2025

DOI: https://doi.org/10.23876/j.krcp.25.080

Dreams disrupted: a comprehensive review of sleep disorders in chronic kidney disease

Georges Kosmadakis

, Clémence Deville, Aura Nécoara, Julien Baudenon, Ioana Enache, Fatima El Kanouni, Joseph El Hajal

AuraSanté, Clermont-Ferrand, France

Correspondence: Georges Kosmadakis AuraSanté, 105 Avenue de la République, 63010, Clermont-Ferrand, France. E-mail: george.kosmadakis@gmail.com

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial and No Derivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted non-commercial use, distribution of the material without any modifications, and reproduction in any medium, provided the original works properly cited.

Abstract

Sleep disorders are common in chronic kidney disease (CKD), significantly affecting quality of life, morbidity, and prognosis. This review examines the classification, prevalence, pathophysiology, diagnosis, and management of insomnia, sleep-disordered breathing including obstructive and central sleep apnea (OSA/CSA), restless legs syndrome (RLS), and excessive daytime sleepiness (EDS) in CKD. Up to 80% of dialysis patients experience sleep disturbances, often underdiagnosed due to overlapping CKD symptoms like fatigue and cognitive dysfunction. Their pathophysiology involves uremic toxin accumulation, fluid overload, electrolyte imbalances, hormonal dysregulation, and chronic inflammation, all contributing to poor sleep. Diagnosis relies on validated tools such as the Pittsburgh Sleep Quality Index, Insomnia Severity Index, STOP-BANG Questionnaire, and Cambridge-Hopkins Restless Legs Syndrome Diagnostic Questionnaire, alongside objective assessments like polysomnography, home sleep apnea testing, and actigraphy. Management requires a multidisciplinary approach. Insomnia is treated with cognitive-behavioral therapy for insomnia, melatonin, and short-term medications. RLS benefits from dopaminergic agents and iron supplementation, while OSA/CSA respond to positive airway pressure (PAP) therapy and nocturnal hemodialysis. Light therapy and intradialytic exercise show promise for EDS. Early recognition and comprehensive management of sleep disorders in CKD are crucial for improving outcomes, reducing cardiovascular risks, and enhancing well-being. Future research should focus on tailored interventions that integrate sleep medicine with nephrology to address this often overlooked aspect of CKD care.

Keywords: Chronic kidney disease, Dialysis, Insomnia, Restless legs syndrome, Sleep apnea, Sleep disorders

Introduction

Chronic kidney disease (CKD) impacts approximately 10% of the global population, affecting both physical and mental health due to the accumulation of waste products, electrolyte imbalances, and changes in hormonal function [1]. One of the most prevalent but often overlooked issues in this population is the high rate of sleep disorders, which affects more than half of CKD patients and up to 80% of those undergoing dialysis [2]. These sleep disorders encompass a range of conditions such as insomnia, restless legs syndrome (RLS), sleep apnea, and excessive daytime sleepiness (EDS) [3]. The presence of sleep disorders in CKD patients affects the overall quality of life, increasing risks for depression, anxiety, and cognitive dysfunction [4]. Studies reveal that CKD patients with sleep disturbances frequently report fatigue, reduced motivation, and emotional distress, leading to decreased adherence to treatment protocols [5].

The burden of sleep disorders among CKD patients is further exacerbated by limited awareness and underdiagnosis. Many symptoms of sleep disorders overlap with CKD-related issues, such as fatigue and general malaise, making accurate diagnosis challenging [6].

This review synthesizes recent findings on the epidemiology, pathophysiology, and management strategies for sleep disorders in CKD patients, with a particular focus on those undergoing dialysis. By clarifying these complex interactions, clinicians can develop more effective, holistic interventions tailored to the unique challenges faced by CKD patients [7].

Classification and definition of sleep disorders in chronic kidney disease

Sleep disorders in patients with CKD encompass a broad range of conditions that significantly impact quality of life, cardiovascular health, and disease progression. The classification of these disorders follows the guidelines established by the International Classification of Sleep Disorders, third edition and includes insomnia, sleep-related breathing disorders (e.g., obstructive sleep apnea [OSA]), movement disorders (e.g., RLS), and circadian rhythm sleep-wake disorders [8] (Table 1).

Insomnia in chronic kidney disease

Insomnia is defined as difficulty initiating or maintaining sleep, early morning awakenings, or poor sleep quality despite adequate sleep opportunity, leading to daytime impairment [9]. It is classified as chronic insomnia disorder when symptoms persist for at least 3 months, occurring at least three times per week [10]. If symptoms last for less than 3 months and are often triggered by stress or medical conditions, it is considered short-term insomnia disorder [11]. In CKD, insomnia is often secondary to factors such as uremic toxins, pruritus, metabolic acidosis, pain, and psychological distress [12].

Sleep-related breathing disorders in chronic kidney disease

This category includes OSA and central sleep apnea (CSA), both of which are highly prevalent in CKD. OSA is characterized by recurrent episodes of upper airway obstruction during sleep, leading to intermittent hypoxia and sleep fragmentation [13]. It is diagnosed when the apnea-hypopnea index (AHI) ≥5 events/hour with symptoms or AHI ≥15 events/hour regardless of symptoms [14]. CSA occurs due to a failure of central respiratory drive, leading to cyclic reductions in ventilatory effort and periodic breathing [15]. It is common in CKD due to fluid shifts, autonomic dysfunction, and metabolic disturbances [16].

Restless legs syndrome and periodic limb movement disorder in chronic kidney disease

RLS is a sensorimotor disorder characterized by an uncontrollable urge to move the legs, often worsening at night and relieved by movement [17]. It can be primary (Idiopathic, often genetic in origin) or secondary RLS, which is more common in CKD and linked to iron deficiency, uremia, and dopamine dysregulation [18]. Periodic limb movement disorder (PLMD) is a repetitive, involuntary leg movements during sleep, often disrupting sleep architecture [19]. It is common in CKD and frequently coexists with RLS, contributing to insomnia and daytime fatigue [20].

Circadian rhythm sleep-wake disorders in chronic kidney disease

These disorders result from misalignment between the endogenous circadian rhythm and external environmental cues [21]. Delayed sleep phase disorder is characterized by difficulty falling asleep and waking up late, frequently reported in CKD patients undergoing nighttime dialysis [22]. Non-24-hour sleep-wake disorder occurs due to irregular melatonin secretion patterns, observed in advanced CKD [23].

Epidemiology of sleep disorders in chronic kidney disease

Sleep disorders are highly prevalent among patients with CKD, with rates significantly exceeding those observed in the general population [24]. The prevalence of these conditions varies based on CKD stage, dialysis dependency, and comorbidities (Table 2, Fig. 1).

Insomnia in chronic kidney disease

Insomnia, characterized by difficulty initiating or maintaining sleep, affects a substantial proportion of CKD patients. Studies estimate that 40% to 60% of non-dialysis CKD patients and 50% to 70% of dialysis-dependent patients experience insomnia compared to 10% to 30% in the general population [12]. A large cross-sectional study reported that 57.4% of CKD patients had sleep disturbances, with 37% meeting the criteria for clinical insomnia [25]. Insomnia is more prevalent in end-stage renal disease (ESRD) patients, especially those on hemodialysis (55%–70%) and peritoneal dialysis (40%–60%) [26].

Obstructive sleep apnea in chronic kidney disease

OSA is one of the most common sleep disorders in CKD, with prevalence rates between 30% and 80%, depending on disease severity [27]. OSA is observed in 30% to 40% of patients with moderate kidney dysfunction [28], whereas in ESRD on hemodialysis the prevalence increases to between 50% and 60%, with a higher frequency of CSA in addition to OSA [29]. In patients on nocturnal dialysis, OSA prevalence remains 40% to 50%, although nocturnal hemodialysis may improve AHI scores by reducing fluid overload and upper airway narrowing [29].

Restless legs syndrome in chronic kidney disease

RLS is significantly more common in CKD than in the general population, affecting 20% to 50% of CKD patients, compared to 5% to 10% in the general population [30]. In non-dialysis CKD, RLS is present in 15% to 30% of patients. Among dialysis patients, prevalence reaches 30% to 50%, with studies reporting even higher rates in certain populations [31].

Excessive daytime sleepiness in chronic kidney disease

EDS is reported in 12% to 50% of CKD patients, depending on disease stage and dialysis modality [32]. In non-dialysis CKD patients, approximately 15% to 25% experience significant daytime sleepiness. For hemodialysis patients, rates range from 35% to 50%, with increased risk due to fragmented sleep, OSA, and metabolic imbalances [33]. Peritoneal dialysis patients report similar or slightly lower rates of EDS compared to hemodialysis, but they still experience high fatigue levels [34].

Diagnostic methods for sleep disorders in chronic kidney disease patients

The diagnosis of sleep disorders in patients with CKD requires a multimodal approach, incorporating clinical assessment, validated screening tools, objective sleep studies, and laboratory biomarkers (Table 3).

Clinical history and validated questionnaires

A comprehensive sleep history, including sleep onset latency, nocturnal awakenings, daytime fatigue, and nocturnal symptoms such as snoring or leg discomfort, provides initial diagnostic clues. Several standardized questionnaires have been validated for screening sleep disorders in CKD patients.

Insomnia

• Insomnia Severity Index: A seven-item questionnaire assessing sleep latency, maintenance, and associated distress, with a score >14 indicating clinically significant insomnia [35].

• Pittsburgh Sleep Quality Index (PSQI): A validated, self-reported questionnaire that assesses subjective sleep quality, sleep latency, duration, efficiency, disturbances, use of sleep medications, and daytime dysfunction over 1 month, with scores >5 indicating poor sleep quality [36].

Obstructive sleep apnea

• STOP-BANG Questionnaire: Evaluates snoring, tiredness, observed apneas, high blood pressure, body mass index (BMI), age, neck circumference, and gender. A score ≥3 suggests a high risk for OSA [37].

• Berlin Questionnaire: Divided into three categories assessing snoring, daytime somnolence, and hypertension/BMI. High risk is determined by positive responses in two or more categories [38].

• Epworth Sleepiness Scale: An eight-question scale quantifying daytime sleepiness, with scores >10 indicating excessive sleepiness and a possible need for further evaluation for OSA or central sleep disorders [39].

Restless legs syndrome

• Cambridge-Hopkins Restless Legs Syndrome Diagnostic Questionnaire: A self-administered tool with high sensitivity (87%) and specificity (94%) for diagnosing RLS in CKD patients [17].

• International Restless Legs Syndrome Study Group criteria: Requires the presence of an urge to move the legs, worsening at rest, occurring predominantly in the evening/night, and relieved by movement [40].

Excessive daytime sleepiness

• Multiple Sleep Latency Test: Measures the time taken to fall asleep in a controlled setting, with a mean sleep latency of ≤8 minutes considered abnormal [41].

Objective sleep studies

Polysomnography (PSG) is the gold standard. Full-night attended PSG is the definitive diagnostic tool for sleep disorders, particularly OSA and PLMD, which frequently coexists with RLS in CKD patients [42].

PSG records multiple physiological parameters:

• Electroencephalography (EEG): Assesses sleep architecture, disruptions, and microarousals [43]

• Electromyography: Detects periodic limb movements, a hallmark of PLMD [19]

• Electrooculography: Monitors rapid eye movement (REM) sleep abnormalities, often altered in CKD [2]

• Pulse oximetry and capnography: Identifies desaturations and hypercapnia, critical in detecting OSA and CSA [44]

• Respiratory effort and airflow sensors: Differentiate between obstructive and central events in sleep apnea [45]

Home sleep apnea testing

Home sleep apnea testing is an alternative to PSG for diagnosing moderate-to-severe OSA in patients with high pre-test probability [46]. While it records airflow, oximetry, and respiratory effort, it lacks EEG monitoring, limiting its utility in detecting non-apneic sleep disorders [47]. CKD patients often require in-lab PSG due to overlapping conditions such as RLS and insomnia.

Actigraphy: a noninvasive sleep-wake cycle assessment

Actigraphy involves wearing a wristwatch-like device that tracks movement over multiple days to assess sleep-wake patterns [48]. It is useful for evaluating insomnia by detecting prolonged sleep onset latency and nocturnal wakefulness, and for identifying circadian rhythm disorders, which are common in CKD patients undergoing nocturnal dialysis [49].

Serum and biomarker analysis

Though not diagnostic per se, laboratory markers can support sleep disorder diagnoses in CKD:

• Ferritin and transferrin saturation: Ferritin <50 ng/mL and transferrin saturation <20% suggest iron deficiency, a common trigger for RLS [50].

• C-reactive protein and interleukin-6 (IL-6): Elevated levels correlate with systemic inflammation, which exacerbates insomnia and sleep apnea in CKD [51].

• Serum melatonin levels: Altered secretion patterns are associated with sleep onset difficulties in CKD [52].

Pathophysiology of sleep disorders in chronic kidney disease

The pathophysiology of sleep disorders in CKD is complex and multifactorial, involving a combination of metabolic, biochemical, hormonal, and inflammatory factors (Table 4). The progression of CKD leads to an array of systemic changes that disrupt sleep regulation and contribute to disorders such as insomnia, RLS, sleep-disordered breathing (SDB), and EDS [53]. These sleep disturbances, in turn, may accelerate the decline of renal function and exacerbate CKD complications, creating a vicious cycle that further challenges disease management [54].

Uremic toxins and sleep dysregulation

One of the primary contributors to sleep disturbances in CKD patients is the accumulation of uremic toxins. Uremic toxins are thought to disrupt neural pathways that regulate sleep, impacting neurotransmitter levels, altering brain structure, and contributing to cognitive impairment and psychological symptoms, all of which are linked to poor sleep quality [55,56].

Fluid overload and sleep-disordered breathing

Fluid overload is particularly problematic in patients with SDB, including OSA. During sleep, fluid can redistribute from the legs to the neck and upper airway, leading to upper airway obstruction and promoting episodes of apnea [57]. The relationship between fluid overload and SDB highlights a bidirectional pathway: SDB exacerbates fluid retention by causing hypoxia-induced renal vasoconstriction, which in turn leads to further declines in kidney function [58]. This process is especially common in hemodialysis patients, as fluid retention between dialysis sessions can exacerbate SDB symptoms, which are further intensified by shifts in body position during sleep [59].

Electrolyte imbalances and restless legs syndrome

Electrolyte imbalances, particularly disturbances in calcium, phosphate, potassium, and magnesium levels, are common in CKD due to impaired renal function and altered metabolism. These imbalances are thought to contribute to the development of RLS [60]. Studies have noted that CKD patients with RLS often have lower magnesium and calcium levels, which may disrupt neuronal excitability and neuromuscular function, leading to the sensory symptoms characteristic of RLS [61].

Iron deficiency is another contributor to RLS in CKD. Reduced renal function can impair iron absorption and metabolism, leading to low serum ferritin levels that correlate with RLS severity [6]. Iron is essential for dopamine synthesis in the brain, and deficiencies in iron and dopamine are thought to be central to RLS pathophysiology [7].

Hormonal dysregulation and circadian disruption

CKD is associated with dysregulation of several hormones that impact sleep, including melatonin, parathyroid hormone (PTH), and the renin-angiotensin-aldosterone system (RAAS). Melatonin, a hormone produced by the pineal gland, is integral to the regulation of circadian rhythms and the sleep-wake cycle. Studies have shown that melatonin secretion is altered in CKD patients, with reduced nighttime levels and blunted circadian rhythms, contributing to insomnia and poor sleep quality [62].

Moreover, CKD patients often experience elevated levels of PTH due to imbalances in calcium and phosphate metabolism. Elevated PTH levels have been linked to sleep disturbances, possibly due to their effects on the central nervous system and alterations in calcium signaling, which can interfere with sleep initiation and maintenance [63].

The activation of the RAAS in CKD also promotes fluid retention and hypertension, which can further exacerbate SDB and disrupt sleep through increased sympathetic activity [64].

Inflammation and oxidative stress

Chronic inflammation and oxidative stress are hallmarks of CKD and play a significant role in the pathophysiology of sleep disorders within this population. CKD patients exhibit high levels of pro-inflammatory cytokines such as IL-6, tumor necrosis factor-alpha, and C-reactive protein, all of which can disrupt sleep architecture by impacting the central nervous system and altering neurotransmitter levels [7]. These cytokines influence the hypothalamic-pituitary-adrenal axis, increasing stress hormone levels and promoting sleep disturbances like insomnia and daytime sleepiness [65].

Oxidative stress, resulting from an imbalance between free radicals and antioxidant defenses, is also prevalent in CKD and has been associated with neurodegeneration and sleep fragmentation [6]. Studies indicate that oxidative stress can lead to changes in brain regions responsible for sleep regulation, such as the hypothalamus, exacerbating symptoms of sleep disorders in CKD [66].

Neural and neurotransmitter alterations

The uremic environment in CKD is known to impact neurotransmitter systems, including dopamine and serotonin, which are crucial for regulating mood, motivation, and sleep. Dopamine dysregulation, in particular, has been implicated in both RLS and insomnia in CKD patients [60]. Low levels of dopamine can lead to disturbances in motor control and mood regulation, contributing to RLS symptoms and fragmented sleep. Additionally, serotonin, a precursor of melatonin, is often dysregulated in CKD, further compounding sleep-wake disturbances and exacerbating insomnia [67].

Treatment for insomnia in chronic kidney disease patients

Effective treatment strategies are essential for improving sleep quality, reducing the risk of complications, and enhancing the overall quality of life for CKD patients. Here, we focus on three primary interventions: melatonin supplementation, cognitive-behavioral therapy for insomnia (CBT-I), and short-term pharmacologic agents (Table 5).

Melatonin supplementation

Melatonin is a hormone naturally produced by the pineal gland, which regulates circadian rhythms and the sleep-wake cycle. CKD patients often exhibit lower levels of melatonin due to disrupted renal metabolism, contributing to insomnia and other sleep disturbances [6]. Melatonin supplementation has shown promise as a treatment for insomnia in this population. Studies indicate that a dose of 3 mg of melatonin taken 30 minutes before bedtime can significantly improve various aspects of sleep quality, including sleep onset latency, sleep duration, and overall sleep efficiency as measured by the PSQI [63]. In addition to improving sleep metrics, melatonin supplementation has been associated with reductions in anxiety and depressive symptoms among hemodialysis patients. The anxiolytic and antidepressant properties of melatonin offer dual benefits, addressing not only insomnia but also the mental health comorbidities often present in CKD patients [68]. Prolonged-release formulations of melatonin may provide further benefits by sustaining melatonin levels throughout the night, thus helping to prevent nocturnal awakenings and enhancing overall sleep maintenance [20]. Melatonin is generally well-tolerated with minimal side effects, making it a viable first-line treatment option for insomnia in CKD, particularly for those looking to avoid traditional sedative-hypnotics [52].

Cognitive-behavioral therapy for insomnia

CBT-I is a structured, non-pharmacologic intervention that focuses on changing thoughts and behaviors contributing to poor sleep. CBT-I has proven effective for insomnia in the general population and is increasingly recognized as a beneficial approach for CKD patients [69]. CBT-I combines several therapeutic techniques, including sleep restriction (limiting time in bed to increase sleep efficiency), stimulus control (associating the bed only with sleep), cognitive restructuring (challenging negative thoughts about sleep), and relaxation training [70]. Through these techniques, CBT-I addresses both the psychological and behavioral aspects of insomnia, making it particularly well-suited for CKD patients who may suffer from stress, anxiety, and other psychological stressors related to their illness [63]. Studies have demonstrated that CBT-I can significantly improve sleep quality and reduce the number of awakenings in CKD patients, resulting in a marked improvement in overall quality of life [6].

Digital and remote CBT-I programs, which can be accessed via computers or tablets, have shown promise in improving sleep outcomes for patients undergoing hemodialysis, providing a feasible and accessible option for this population [71]. A notable advantage of CBT-I is its long-lasting effects; unlike pharmacologic treatments, which may require ongoing use, the benefits of CBT-I can persist beyond the treatment period, offering sustained relief from insomnia [72].

Short-term pharmacologic agents: Z-drugs and benzodiazepines

For CKD patients who require immediate relief from severe insomnia, short-term pharmacologic agents such as Z-drugs (non-benzodiazepine hypnotics like zolpidem and eszopiclone) and benzodiazepines may be considered. These drugs act by enhancing gamma-aminobutyric acid activity, promoting relaxation and sedation, thereby facilitating sleep [73]. Z-drugs, in particular, are often preferred due to their relatively favorable safety profile and lower risk of dependency compared to benzodiazepines [74]. However, due to impaired renal clearance, CKD patients are at an increased risk of prolonged sedation and side effects, including dizziness, confusion, and falls, especially in older adults [75]. Z-drugs are typically considered safer than benzodiazepines for short-term use, as they are less likely to affect respiratory function, which is crucial in CKD patients who may also have sleep apnea [76]. Nonetheless, their use should be limited to the lowest effective dose and shortest duration possible, generally recommended for no longer than 2 weeks, to mitigate the risk of dependence and withdrawal symptoms.

Benzodiazepines, such as lorazepam and temazepam, may be effective for acute insomnia but carry a higher risk of dependence and are associated with a range of adverse effects, including respiratory depression, especially in patients with concurrent sleep apnea [76].

Management of restless legs syndrome in chronic kidney disease patients

Management of RLS in CKD requires a multi-pronged approach that includes pharmacological interventions, iron supplementation, and non-pharmacological therapies (Table 6).

Dopaminergic agents

Dopaminergic agents, such as pramipexole and ropinirole, are commonly used to manage RLS symptoms in both the general population and CKD patients. These medications work by stimulating dopamine receptors in the brain, which helps to alleviate the uncomfortable sensations associated with RLS [40]. Dopamine dysregulation is believed to play a role in RLS pathophysiology, and dopaminergic agents can restore some balance, thereby reducing the urge to move and improving sleep quality in CKD patients [77]. The efficacy of dopaminergic agents in reducing RLS severity and improving sleep quality in CKD patients is well-documented. Studies indicate that pramipexole and ropinirole are effective in reducing RLS symptoms and improving patient-reported sleep quality [78]. However, these medications must be used with caution in CKD due to potential side effects such as nausea, dizziness, and, importantly, augmentation—where symptoms worsen over time with long-term use [65,79].

Iron supplementation

Iron deficiency is a well-known contributor to RLS in CKD, as iron plays a crucial role in dopamine synthesis. Low serum ferritin and transferrin saturation levels are often found in CKD patients with RLS, exacerbating symptoms [60]. Iron supplementation, particularly intravenous iron, is recommended for CKD patients with RLS and low iron stores, as it bypasses the issues of reduced gastrointestinal absorption that are common in CKD [80]. Intravenous iron sucrose and ferric carboxymaltose are common options, with studies demonstrating that they can significantly reduce RLS severity and improve sleep quality in hemodialysis patients [56]. Oral iron supplements may also be used; however, they are generally less effective in CKD patients due to impaired gastrointestinal absorption and may not achieve adequate iron levels for symptom control [81].

Physical and alternative therapies

Non-pharmacological therapies, including physical and alternative treatments, provide additional options for RLS management in CKD. Physical activity, particularly intradialytic exercise (exercise performed during dialysis sessions), has been shown to alleviate RLS symptoms and improve sleep quality. Intradialytic exercise may include activities such as cycling or resistance exercises, which help reduce the frequency and severity of RLS episodes, likely by enhancing blood flow and reducing uremic toxin buildup in the muscles [61]. Alternative therapies, such as acupuncture and acupressure, have been explored for their potential to relieve RLS symptoms. These techniques involve stimulating specific points on the body, which is thought to modulate pain pathways and enhance relaxation [82]. Though the evidence is limited, preliminary studies suggest that acupuncture may reduce leg discomfort and improve sleep quality in CKD patients with RLS [83].

Approaches for sleep-disordered breathing and obstructive sleep apnea in chronic kidney disease patients

Managing SDB in CKD involves a combination of fluid management, positive airway pressure (PAP) therapies, and dialysis modifications, particularly nocturnal hemodialysis. Each of these interventions addresses specific contributors to SDB and can improve sleep quality, oxygenation, and overall health outcomes in CKD patients (Table 7).

Fluid management: dietary and dialysis modifications

Fluid overload is a common issue in advanced CKD and is particularly problematic for patients with SDB and OSA. Fluid retention can contribute to the collapse of the upper airway during sleep, worsening OSA and other forms of SDB [57].

Dietary modifications are often the first step in managing fluid overload. CKD patients are typically advised to follow a low-sodium diet to limit fluid retention, as sodium intake is directly related to fluid volume control. Studies indicate that reducing sodium intake can help minimize fluid shifts, decreasing the likelihood of upper airway obstruction during sleep [84].

Dialysis-related modifications, particularly adjusting the timing and frequency of dialysis sessions, play a significant role in fluid management for CKD patients with SDB. Increasing the frequency of dialysis sessions, or opting for daily or nocturnal dialysis, helps achieve better fluid removal and prevents fluid overload between sessions [85]. Frequent dialysis has been shown to reduce edema and improve upper airway patency, thus decreasing the frequency of apnea episodes and improving oxygenation levels during sleep [86].

Positive airway pressure therapy: continuous positive airway pressure and bilevel positive airway pressure

PAP therapy, which includes continuous PAP (CPAP) and bilevel PAP (BiPAP), is the standard treatment for OSA and is also effective for managing other forms of SDB in CKD patients [87]. PAP therapy works by delivering a constant flow of air through a mask, which keeps the upper airway open and prevents the collapse associated with apnea episodes. CPAP is generally recommended as the first-line treatment for OSA, while BiPAP may be more suitable for patients who have difficulty tolerating the higher pressures required with CPAP or who have concurrent conditions like heart failure that require variable pressure levels [88]. Studies have demonstrated that CPAP use in CKD patients with SDB can significantly reduce AHI scores, improve oxygen saturation, and enhance overall sleep quality [89]. Improved oxygenation from CPAP use has beneficial effects on cardiovascular health, reducing the sympathetic overactivity often triggered by nocturnal hypoxia in SDB patients. This reduction in sympathetic drive may also help stabilize blood pressure, a critical factor for CKD patients who are at high risk of hypertension [90]. While CPAP is effective, adherence can be a challenge in the CKD population. Factors such as discomfort, skin irritation, and nasal dryness can reduce CPAP compliance, making it important for healthcare providers to offer support and education on mask fitting, device maintenance, and managing side effects [91]. BiPAP is sometimes preferred in CKD patients with high pressures or those who experience CSA in addition to OSA, as it allows for different pressures during inhalation and exhalation, which can improve comfort and tolerance [92].

Nocturnal hemodialysis: effectiveness for sleep-disordered breathing and improvements in oxygenation and fluid management

Nocturnal hemodialysis, which involves longer dialysis sessions performed at night, is an effective alternative to conventional daytime dialysis for CKD patients with SDB. This approach has gained traction for its potential to improve both sleep quality and overall health outcomes by enhancing fluid management, reducing blood pressure, and minimizing toxin buildup [93]. Studies indicate that nocturnal hemodialysis can significantly reduce the AHI in CKD patients with OSA, suggesting that this approach can reduce the frequency of apnea episodes and improve sleep continuity [29]. Additionally, patients who switch to nocturnal dialysis often experience improved oxygenation levels [94]. Another advantage of nocturnal hemodialysis is its effect on blood pressure control. SDB and OSA are associated with elevated sympathetic activity and hypertension, both of which exacerbate CKD progression. Nocturnal hemodialysis has been shown to lower blood pressure, which can have additional benefits for CKD patients by reducing cardiovascular strain and potentially slowing disease progression [68]. Patients on nocturnal hemodialysis report fewer awakenings and less daytime fatigue, potentially due to reduced uremic symptoms and better control of fluid and electrolyte levels [95].

Management of excessive daytime sleepiness in chronic kidney disease patients

EDS in CKD patients often results from a combination of poor nighttime sleep quality, uremic toxins, metabolic imbalances, and the burden of dialysis, which together contribute to persistent fatigue, reduced alertness, and diminished quality of life. Managing EDS in CKD involves multiple strategies, including light therapy, intradialytic exercise, and behavioral interventions, each addressing specific factors that contribute to daytime sleepiness and disrupted sleep-wake cycles.

Light therapy: circadian rhythm regulation and reduction of daytime sleepiness

Light therapy is a noninvasive intervention that involves exposing patients to bright light at specific times of the day to help regulate circadian rhythms and improve sleep-wake cycles. CKD patients, especially those undergoing dialysis, often experience disrupted circadian rhythms due to treatment schedules and altered melatonin production, leading to fragmented sleep and subsequent daytime sleepiness [79]. Studies have shown that morning exposure to bright light, typically around 5,000 to 10,000 lux for 20 to 30 minutes, can significantly reduce EDS in CKD patients by enhancing alertness and supporting a healthier sleep-wake pattern [96]. This therapeutic approach has proven particularly beneficial for dialysis patients, who may struggle to maintain consistent circadian rhythms due to the disruptive nature of dialysis schedules [97,98]. Implementation of light therapy can be customized based on the patient’s daily routine and dialysis schedule. Home-based light therapy devices are available, allowing patients to undergo treatment at their convenience. Though generally safe, some patients may experience mild side effects such as headaches or eye strain; these can often be managed by adjusting light intensity or session duration [98].

Intradialytic exercise and physical activity: effects on fatigue, alertness, and sleep quality

Physical activity, particularly intradialytic exercise (exercise performed during dialysis sessions), has been shown to positively impact fatigue levels, alertness, and sleep quality in CKD patients. Exercise helps reduce uremic toxins, improves cardiovascular health, and enhances mood, all of which contribute to reduced EDS and improved overall well-being. Intradialytic exercise typically includes low-to-moderate intensity activities such as stationary cycling or resistance training, which are feasible to perform during dialysis without interrupting the treatment [99]. Research indicates that intradialytic exercise significantly improves alertness and reduces fatigue, as it stimulates blood circulation and increases oxygenation to the brain, which can enhance cognitive function and mental clarity [100]. Additionally, regular physical activity has been associated with improvements in nighttime sleep quality and duration, helping to establish a healthier sleep pattern and reducing the need for daytime napping [101].

Conclusion

Sleep disorders, including insomnia, RLS, SDB, and EDS, are pervasive and disruptive complications for patients with CKD. The multifactorial pathophysiology of these disorders—stemming from metabolic imbalances, uremic toxins, fluid overload, and circadian disruptions—demands a tailored, multifaceted approach to treatment. Pharmacologic interventions, such as melatonin, dopaminergic agents, and iron supplementation, offer effective symptom management, while non-pharmacological strategies, including cognitive-behavioral therapy, light therapy, intradialytic exercise, and nocturnal hemodialysis, address underlying physiological and behavioral contributors to sleep disruption. A comprehensive and individualized treatment approach can significantly improve the quality of life, physical health, and treatment adherence for CKD patients, underscoring the importance of integrated sleep management in CKD care.

Notes

Conflicts of interest

All authors have no conflicts of interest to declare.

Data sharing statement

All the presented data is resourced from validated medical references issued from PubMed.

Authors’ contributions

Conceptualization: GK, JB

Data curation, Investigation: GK

Formal analysis: JB

Methodology: GK, CD

Project administration: CD

Supervision: GK, CD, AN, JB, IE, FEK

Validation: GK, CD, AN, IE, FEK, JEH

Visualization: GK, AN, IE, FEK, JEH

Writing–original draft: GK

Writing–review & editing: All authors

All authors read and approved the final manuscript.

Figure 1.

Prevalence of sleep disorders in CKD vs. general population.

CKD, chronic kidney disease; EDS, excessive daytime sleepiness; OSA, obstructive and central sleep apnea; RLS, restless legs syndrome.

Table 1.

Classification of sleep disorders in CKD patients

Sleep disorder	Specific condition	Definition and relevance to CKD
Insomnia disorders	Chronic insomnia	Difficulty falling asleep, staying asleep, or waking too early. Common in CKD due to pruritus, uremic toxins, pain, or psychological stress.
Insomnia disorders	Short-term insomnia
Sleep-related breathing disorders	Obstructive sleep apnea (OSA)	OSA is due to upper airway obstruction; CSA results from reduced respiratory drive. Prevalent in CKD from fluid overload, metabolic imbalance, and autonomic dysfunction.
	Central sleep apnea (CSA)
	Cheyne-stokes respiration
Movement disorders	Restless legs syndrome (RLS)	RLS causes an urge to move legs (linked to iron deficiency in CKD). PLMD involves involuntary limb movements disrupting sleep.
	Periodic limb movement disorder (PLMD)
	Sleep bruxism
Circadian rhythm sleep-wake disorders	Delayed sleep phase disorder	Dialysis and altered melatonin rhythms can disturb sleep-wake cycles in CKD patients.
Circadian rhythm sleep-wake disorders	Non-24-hour sleep-wake disorder
Excessive daytime sleepiness	Narcolepsy	Persistent daytime drowsiness, often related to poor nocturnal sleep, metabolic issues, and dialysis-related fatigue.
Excessive daytime sleepiness	Idiopathic hypersomnia

CKD, chronic kidney disease.

Table 2.

Prevalence of sleep disorders in CKD patients

Sleep disorder	Prevalence in non-dialysis CKD (%)	Prevalence in dialysis patients (%)	Prevalence in general population (%)
Insomnia	40–60	50–70	10–30
Obstructive sleep apnea	30–40	50–60	4–7
Restless legs syndrome	15–30	30–50	5–10
Excessive daytime sleepiness	15–25	35–50	10–15

Table 3.

Diagnostic methods for sleep disorders in CKD patients

Diagnostic category	Diagnostic methods	Use in CKD patients
Clinical history and questionnaires	Insomnia Severity Index (ISI)	Initial screening and subjective assessment of sleep disturbances
	Pittsburgh Sleep Quality Index (PSQI)
	STOP-BANG, Berlin Questionnaire
	Epworth Sleepiness Scale (ESS)
	Cambridge-Hopkins Restless Legs Syndrome Diagnostic Questionnaire
Objective sleep studies	Polysomnography (PSG)	Gold standard for diagnosing OSA, central sleep apnea, periodic limb movement disorder, and other sleep-related disorders
	Multiple Sleep Latency Test (MSLT)
	Electroencephalography (EEG)
	Electromyography (EMG)
	Electrooculography (EOG)
	Pulse oximetry
Home sleep apnea testing	Portable device measuring airflow, oxygen desaturation, respiratory effort; useful for diagnosing moderate-to-severe OSA	Alternative diagnostic tool for high-risk OSA patients, but lacks EEG monitoring
Actigraphy	Wearable movement tracker assessing sleep-wake patterns over multiple days; useful for circadian rhythm disturbances and insomnia	Noninvasive method for evaluating insomnia, circadian rhythm disruptions, and dialysis-related sleep disturbances
Serum and biomarker analysis	Ferritin and transferrin saturation (for RLS), C-reactive protein and interleukin-6 (for inflammation), serum melatonin (for circadian rhythm disruption)	Biomarkers can indicate underlying causes of RLS, inflammation-related insomnia, and melatonin secretion abnormalities

CKD, chronic kidney disease; OSA, obstructive sleep apnea; RLS, restless legs syndrome.

Table 4.

Pathophysiology of sleep disorders in CKD

Pathophysiological factor	Mechanism	Impact on CKD patients
Uremic toxins	Disrupts neural pathways regulating sleep, impacts neurotransmitter levels, contributes to cognitive impairment and poor sleep quality	Linked to insomnia, fatigue, and cognitive dysfunction; worsens quality of life
Fluid overload	Leads to fluid shifts causing airway obstruction, increasing risk of obstructive and central sleep apnea	Exacerbates sleep-disordered breathing, increases cardiovascular risks, and accelerates CKD progression
Electrolyte imbalances	Calcium, phosphate, potassium, and magnesium imbalances contribute to neuronal excitability, worsening RLS symptoms	Worsens motor control, increases muscle cramps, and disrupts sleep onset and maintenance
Hormonal dysregulation	Melatonin disruption affects circadian rhythms, while parathyroid hormone and renin-angiotensin-aldosterone system dysregulation exacerbate sleep disturbances	Results in fragmented sleep, fatigue, and worsening cardiovascular complications in CKD
Inflammation and oxidative stress	Elevated pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-α, C-reactive protein) alter sleep architecture, increase stress hormones, and cause insomnia and daytime sleepiness	Promotes sleep fragmentation, excessive daytime sleepiness, and overall reduced sleep efficiency
Neural and neurotransmitter alterations	Dopamine and serotonin imbalances contribute to RLS, mood changes, and disrupted sleep patterns	Affects sleep-wake cycles, worsens sleep fragmentation, and contributes to psychiatric comorbidities such as depression and anxiety

CKD, chronic kidney disease; RLS, restless legs syndrome.

Table 5.

Treatment approaches for insomnia in CKD patients

Treatment approach	Mechanism of action	Effectiveness in CKD	Safety considerations
Melatonin supplementation	Regulates circadian rhythms by supplementing deficient melatonin levels in CKD patients	Improves sleep onset latency, duration, and efficiency; reduces anxiety and depressive symptoms	Generally well-tolerated with minimal side effects; prolonged-release formulations help maintain nighttime melatonin levels
Cognitive-behavioral therapy for insomnia (CBT-I)	Behavioral intervention that modifies negative thoughts and habits related to sleep, promoting long-term improvement	Proven long-lasting benefits in improving sleep quality, reducing awakenings, and managing stress/anxiety	Safe and effective; digital and remote CBT-I programs enhance accessibility for dialysis patients
Short-term pharmacologic agents (Z-drugs and benzodiazepines)	Enhances gamma-aminobutyric acid activity to promote relaxation and sedation, facilitating sleep onset	Provides immediate relief for severe insomnia but has potential side effects and risks of dependency	Requires careful use in CKD due to prolonged sedation, increased fall risk, and respiratory depression, especially in older adults

CKD, chronic kidney disease.

Table 6.

Management of RLS in CKD patients

Treatment approach	Benefits	Considerations
Dopaminergic agents (pramipexole, ropinirole)	Reduces RLS symptoms	Risk of nausea, dizziness
Dopaminergic agents (pramipexole, ropinirole)	Improves sleep quality	Requires careful monitoring in CKD
Iron supplementation (IV iron sucrose, ferric carboxymaltose)	Addresses iron deficiency contributing to RLS	Oral iron- poor absorption in CKD
	IV iron more effective in CKD	IV iron requires monitoring for iron overload
Physical and alternative therapies (intradialytic exercise, acupuncture, acupressure)	Improves circulation and reduces RLS severity	Limited high-quality evidence
	Non-pharmacologic, no drug-related side effects	Requires patient adherence and accessibility to resources

CKD, chronic kidney disease; IV, intravenous; RLS, restless legs syndrome.

Table 7.

Therapeutic approaches for sleep-disordered breathing and obstructive sleep apnea in CKD patients

Treatment approach	Benefits	Considerations
Fluid management (dietary and dialysis modifications)	Reduces fluid retention and airway obstruction	Requires adherence to low-sodium diet and dialysis adjustments
Fluid management (dietary and dialysis modifications)	Improves oxygenation and apnea severity	Effectiveness depends on patient compliance
Positive airway pressure therapy (PAP): continuous PAP (CPAP) and bilevel PAP (BiPAP)	Reduces apnea episodes and improves sleep quality	CPAP adherence is a challenge due to discomfort
	Enhances oxygenation and cardiovascular outcomes	BiPAP may be needed for patients with central sleep apnea
Nocturnal hemodialysis	Improves fluid management and reduces apnea-hypopnea index	Requires access to nocturnal dialysis programs
Nocturnal hemodialysis	Enhances oxygen levels and lowers blood pressure	May not be available for all patients

BiPAP, bilevel positive airway pressure; CPAP, positive airway pressure.

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