Sleep Issues and Chronic Kidney Disease

People with chronic kidney disease (CKD) often have trouble falling asleep and staying asleep. Your physical and mental health can contribute to your sleep problems. These are some common causes for disrupted sleep patterns in kidney disease patients.

Sleep disorders are prevalent in patients with chronic kidney disease (CKD) in particular those with end stage renal disease (ESRD). It has been reported that 80% of ESRD patients receiving dialysis report sleep complaints, with daytime sleepiness to be the most common reported symptom. The reason for increased rates of sleep related issues and disorders in this population is likely multi-factorial and will be discussed in this review. Sleep issues are not only related to decreased quality of life, but are also associated with increased health related risks, and mortality in CKD.

Restless leg syndrome

Restless leg syndrome (RLS) often occurs when the legs are at rest, such as when a person is sitting or lying in bed. The sensation varies from patient to patient. It can be irritating, itchy or painful. Some patients find that moving their legs makes the uncomfortable sensations lessen or go away entirely.

Doctors have determined that iron deficiency, caffeine, alcohol, tobacco, diabetes and certain medications can contribute to RLS.

Restless leg syndrome (RLS), also known as Willis-Ekbom syndrome, is a sensory-motor disorder manifested by unpleasant nocturnal sensations in the lower limbs that are relieved by movement. These sensations generally occur deep within the muscle of the leg, but patients occasionally report feeling them on the skin. Two-thirds of patients experience the sensation bilaterally; one-third of patients have unilateral symptoms. The most common site of symptoms is the upper calf, with 75% of patients reporting sensations there. About 80%-90% of RLS patients present with periodic limb movements of sleep (PLMS).

In the general population, symptoms most frequently appear after the age of 45, with 38% of sufferers report onset of symptoms before age 20. RLS is twice as common in females than in males. Family history of RLS is common; 63% of patients report at least one first degree relative with RLS. No monogenic cause has yet been found, but studies show six different genes that may play a role.

In HD patients, the prevalence of RLS is 20%-30%, compared to 3%-7% in the general population. In kidney transplant patients, the prevalence is close to 5%, approximately average for the general population.

RLS impacts sleep, which can lower sleep quality and efficiency as well as overall quality of life. Untreated RLS is highly associated with depression, both in the general population and in patients with CKD. In addition, RLS is associated with higher mortality in ESRD patients

Brain iron dysregulation plays a role in RLS, possibly during transport across the blood brain barrier. Since iron is an essential cofactor in the production of dopamine, low iron levels could explain the changes in dopamine metabolism that occur in RLS. The syndrome is worsened by iron deficiency and symptoms are improved by iron supplementation. RLS sufferers show a drop in CSF ferritin levels throughout the night, while healthy controls do not. Circadian changes in brain iron status are what make this a circadian disease. Other possible factors associated with the condition are elevated serum calcium levels and PNS/CNS abnormalities. ESRD patients may be particularly susceptible to acquiring RLS because peripheral neuropathy complicates and overlaps the picture of RLS.

 

Non-pharmacological treatments

Both aerobic exercise and resistance training have been shown to improve symptoms of RLS. Improvement of sleep hygiene is also thought to have some beneficial effect. There have been no controlled studies on the effects of alcohol, nicotine, and caffeine, but these substances are thought to aggravate the condition. Small studies have shown that pneumatic compression devices, acupuncture, and near-infrared light can be helpful to RLS sufferers.

 

Pharmacological treatments

Dopamine agonists (DAs) are commonly considered to be the first pharmacological option, and they simultaneously address the symptoms of PLMS as well.  Although DAs are an effective initial treatment, they are only shown to be effective in the long term in 25% of patients. In addition, long-term use brings about a worsening of symptoms, known as augmentation, in a large percentage of patients. About 6%-17% of RLS patients who take DAs develop impulse control disorders. Correcting iron deficiency has been shown to improve RLS in HD patients.  Other pharmacological therapies include calcium channel alpha-2-delta ligands (gabapentin, and pregabalin), opioids, and iron therapy. Gabapentin, an alpha-2-delta ligand, is a good choice for patients with polyneuropathy in addition to RLS. In general, both and gabapentin and pregabalin appear to be helpful in improving sleep quality in ESRD patients with painful peripheral neuropathy. However, dosages of both medications need to be renally-adjusted, and side-effect profile has not been adequately described in CKD studies.

 

Augmentation

Augmentation refers to the severe exacerbation of RLS symptoms, sometimes up to 24 h a day, caused by the medication used to treat initial symptoms. It is thought to be the result of pharmacological treatment, not a natural progression of the disease. This is a common complication seen in patients treated with dopaminergic drugs. Augmentation is characterized by gradually earlier onset of symptoms, greater severity of symptoms, increasingly shorter periods of rest between symptoms, expansion of symptoms to upper limbs, and shorter periods of effectiveness of medication. One study found prevalence of augmentation in patients treated with DAs to be as high as 76%. Because of this, DAs should be prescribed only when necessary and patients’ symptoms should be monitored closely.

Large, methodologically sound studies are still needed to further assess the effectiveness of both pharmacological and non-pharmacological treatment options, as well as the impact of different renal replacement modalities.

Sleep apnea

Sleep apnea causes your breathing to be interrupted or stopped for more than 10 seconds while you’re in a deep sleep. These non-breathing intervals are called apneas. Patients with sleep apnea often snore heavily. The snores continue until breathing is interrupted or stops, which signals an apnea. The person will then snort or gasp to take in air and the snoring continues until the next apnea.

A doctor can determine if you have sleep apnea by conducting a physical exam and a sleep study.

Sleep apnea is a chronic sleep disorder which causes repeated cessation of breath while a person is sleeping. Characteristics of sleep apnea include loud snoring, breathlessness, waking up from sleep, and daytime sleepiness. Prevalence in the general population is approximately 2%-4%, compared to the prevalence in ESRD patients which is estimated between 50%-60%, through self-report questionnaires, and about 70%-80% of ESRD patients when based on polysomnography.

Sleep apnea is divided into three sub-types: Central sleep apnea (CSA), obstructive sleep apnea (OSA) or mixed. While OSA is the most common form of sleep apnea in the ESRD population, CSA may be underreported in patients with ESRD, as it can only be diagnosed with polysomnography tests. OSA causes repeated episodes of apneas, carousals, and loud snoring. In contrast to CSA, OSA is commonly recognized by an individual’s bed partner. The most conclusive method of diagnosing OSA remains overnight polysomnography studies.

Sleep apnea in the ESRD can cause excessive sleepiness and cognitive impairment, diminishing daytime functioning. OSA is also commonly linked to depression, hypertension and increased cardiovascular morbidity and mortality.

The direct relationship between sleep apnea and ESRD is not clear. However, several studies have examined “rostral fluid shift” as a possible mechanism in the pathogenesis of OSA in CKD patients. Due to their reclined position overnight, excess fluid shifts from the legs towards the neck leading to upper airway restriction and collapse.

Thus, when CKD patients accumulate excess fluid in the neck due to rostral shift, upper airway “collapsibility” increases leading to high rates of OSA occurrences. One study tested this theory by measuring the neck circumference (NC) and leg fluid volume (LFV) in ESRD patients with OSA. The change in LFV correlated with significant change in NC, supporting the notion that leg fluid is displaced into the neck overnight. Another study conducted by Elias et al confirmed the rostral fluid shift by measuring internal jugular vein volume (iJVVOL) and upper airway mucosal water content (UA-MWC). They found that greater iJVVOL and UA-MWC levels correlated to greater apnea-hypopnea index. Both studies concluded that fluid accumulation in the neck due to rostral shift predisposes ESRD patients to OSA.

 

Treatments

Similar to the general population, continuous positive airway pressure (CPAP) is the first line of treatment in CKD patients with OSA. Other treatment modalities in the general population include the use of dental appliances, oral surgery, and treating underlying medical conditions (e.g., obesity or hypothyroidism). These modalities have not yet been extensively studied in the CKD population.

Research has shown that conversion from conventional HD to nocturnal HD (NHD) reduces the occurrence of apneas. One suggested mechanism is that NHD aggressively removes more uremic toxins than conventional HD which may contribute to better sleep quality. Studies that examined ESRD patients before and after conversion to NHD, found that NHD was effective in lowering the heart rate and reducing the frequency of apneas and hypoxemias in all of the patients.

Inadequate dialysis clearance

A build up of waste in the blood can cause you to feel ill and uncomfortable. This could make sleeping difficult. If you’re on peritoneal dialysis (PD), your doctor will occasionally test your dialysate to make sure it is pulling enough waste and toxins from your body.

Emotions

Worry, anxiety and sadness can keep you up at night. If your sadness, anxiety or depression lasts more than two weeks, tell your doctor immediately.

Changes in your sleep pattern

Sometimes patients who have CKD are more tired than usual. They tend to fall asleep earlier than their normal bedtime or nap during the day. If you feel that a nap can help you, limit your nap time. Naps that last longer than an hour can disrupt your sleep cycle.

Caffeine

Caffeine is a stimulant; it jump starts your body, making you feel more alert. Many people drink caffeinated beverages in the morning to wake up, and then reach for a late afternoon caffeine “pick me up.” Unfortunately, too much caffeine late in the day can affect your ability to fall asleep  at night. In the morning, the caffeine cycle starts again.

If you’re having trouble sleeping, try reducing the amount of caffeine in your diet.  Keep an accurate food diary to show your renal dietitian.

Tips for getting and staying asleep

The following are things you can do if you experience sleeplessness:

Expend energy during the day with exercise

Exercise can help you feel tired so that you can fall asleep faster and sleep soundly. Ask your doctor about starting an exercise program. They can recommend a program based on your physical abilities and current state of health.

Adjust your sleep clock

You can train your body to get the right amount of sleep each night. This means keeping to a sleep schedule. You should go to bed at the same time each night and wake up at the same time each morning.

Limit your nap times

Too long of a nap can mean you won’t be able to fall asleep later that night. Try to limit the number of naps and the amount of time you sleep during the day.

Cut back on caffeine, alcohol and tobacco

Caffeine and nicotine (found in tobacco) can keep you awake longer than you wish. Cutting back can help you return to normal sleep patterns. Try limiting your caffeine intake to 2 cups a day before noon and avoid smoking before bedtime or during the night. Limit your alcohol intake as well, especially before bedtime, because it can disrupt your sleep.

Find ways to relax before bedtime

Relaxing is an important part of getting to sleep. Find a light activity that you can enjoy before bedtime.

Comfortable surroundings can mean a sounder night’s sleep

A comfortable bed and bedding can lessen the amount of times you get up during the night. A darkened, quiet room will have fewer distractions to wake you up.

If you still have trouble sleeping, or if you experience insomnia for a week or more, tell your doctor. Adequate rest is an important part in your CKD treatment.

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