To our knowledge, this is the first study to focus on sleep problems in RTx recipients by using a detailed sleep questionnaire (SOS) and subsequent sleep assessment interview. This study describes the frequency of self-reported sleep disturbances in RTx recipients screened with the Survey of Sleep questionnaire (SOS) and the frequency of presumed sleep diagnoses based on the sleep interview.
As shown in Table 1, of the 688 patients invited to participate, roughly 50% (n = 325) registered poor SQ and DS. Figure 1 shows an increasing proportion of participants in the “poor SQ (PSQI > 5) & and DS (ESS ≥ 6)” group. Of these 325, 153 (47.1%) filled in the SOS and 108 (70.6%) participated in the assessment interview. In addition, poor SQ was significantly more prevalent in participants compared to non-participants. This would support a hypothesis that, even where no therapeutic benefit can be hoped for, patients are more likely to participate in studies directly relevant to their personal experience.
Prevalence and percentages of sleep problems and sleep habits [SOS part 1]
The most prevalent sleep problem was difficulty staying asleep, followed by problems falling asleep. Both are characteristic of insomnia . Other characteristics of insomnia common in this group were the extended duration of the sleep problem (61.4% reported durations greater than 2 years), the severity of the sleep problem (26.9% called their problems severe), the high prevalence of nightly sleeping pill use (32.9%), sleep latency of 28 ± 19.3 minutes, a high number of awakenings (2.8 ± 1.8) per night, long sleep latency after awakening (21.9 ± 16.4 minutes), and high ratios of time in bed to hours of sleep (8.3 ± 1.3 hours) to hours of sleep 6.4 ± 1.5. These results corroborate those of Moul et al. (2002),  who reported that 68% of insomnia patients exhibited long-term sleep problems (more than 1 year), severe sleep problems (81%), high nightly use of sleeping pills (89%), long sleep latency (53.3 ± 51.8 minutes), high numbers of awakenings (2.7 ± 1.7) per night, long sleep latency after awakening (56.0 ± 64.7 minutes), and high ratios of time in bed to hours of sleep (8.2 ± 1.9 hours in bed: 5 ± 1.7 hours of sleep). The average sleep duration of 6.4 ± 1.5 is very low, as studies have shown that chronic restriction of sleep to 6 h or less per night produces cognitive performance deficits equivalent to up to 2 nights of total sleep deprivation . Sleep deficits seriously impair waking neurobehavioral functions (lapses in behavioral alertness) in healthy adults .
Prevalence and percentages of sleep habits [SOS part 2]
One third of participants (n = 82) reported using sleeping pills; however, the medical chart data showed that very few (n = 9) had informed their nephrologists regarding their sleep problems or use of sleep medication. During their post-transplant hospitalization, all RTx recipients receive education regarding over-the-counter medication and medication prescriptions from other physicians, during which they are advised always to consult their nephrologist about possible interactions with their immunosuppressive drugs . This discrepancy may indicate that patients are reluctant to bring up sleep problems, that they do not see sleep disorders as a topic that nephrologists can deal with, or that the nephrologists themselves simply consider sleep disorders a normal side effect of RTx immunosuppressive regimens. Compared to the general population, our prevalence of 32.9% self-reported sleep medication use is very plausible: sleep medications are used regularly by 3.2% of subjects 44 or younger, 13.3% of subjects between 45 and 64, 22% of those between 65 and 74 and 32% of individuals 75 or older .
Prevalence and percentage of sleep symptoms [SOS part 3]
The most prevalent night-time symptom was nocturia. The frequency of its occurrence is key to further diagnosis. Nocturnal polyuria (nocturnal urine overproduction) and diminished nocturnal bladder capacity  require further testing to exclude urinary tract infections and prostate hyperplasia . Also very prevalent were leg cramps and frequent turning in bed, indicating muscle fatigue, nerve dysfunction or electrolytic imbalances . However, these symptoms could also be indices of restless leg syndrome, periodic limb movements, myositis, or peripheral neuropathy . Similarly, turning or rocking in bed could indicate parasomnia (undesirable physical or behavioral phenomena occurring during the sleep period) . For the diagnosis of parasomnias a careful physical examination is crucial and often a polysomnogram, including an expanded electroencephalographic montage, is necessary to distinguish between parasomnias (non-REM or REM) and nocturnal seizures .
Leg cramps during sleep were the second most prevalent sleep symptom (37.8%), followed by frequent tossing and turning in bed (37.1%). These two symptoms could be related to restless leg syndrome and/or periodic limb movements. The prevalence of restless leg syndrome in RTx recipients overall is 4.5% . For periodic limb movements the overall prevalence is unknown, although there is an improvement from pre- to post-Tx . Nocturnal leg cramps are often associated with vascular disease, lumbar canal stenosis, cirrhosis and hemodialysis , however no prevalence is known for RTx recipients. The sensorimotor symptoms of restless leg syndrome and/or periodic limb movements can be treated with dopamine agonists, gabapentin and its derivatives, and opioids . To summarize, in-depth assessment of all these listed symptoms is crucial for the right treatment choice.
Prevalence and percentage of daytime function [SOS part 4]
Table 4 shows the high prevalence of daytime sleepiness, tiredness and impaired daytime functioning, highlighting the importance for affected patients to use reminders (e.g., pillbox alarms, SMS reminder functions, or other cues) to ensure punctual intake of their immunosuppressive drugs. An earlier study showed correlations between DS and impaired immunosuppressive medication adherence [Burkhalter H, Wirz-Justice A, Cajochen C, Weaver T, Steiger J, Fehr T, Venzin R, De Geest S: Daytime sleepiness is associated with immunosuppressive non-adherence in renal transplant recipients: a cross-sectional multi-center study. Submitted]. However, it is possible that compensating behaviors such as increased use of mild stimulants (e.g., caffeine, nicotine) (Table 1) account for the lower prevalence of non-adherence (16%) than of DS (52%) .
Napping behavior and sleep duration depends on cultural, environmental, occupational and health factors . In this study, 47.4% of participants reported intentional napping, a behavior shown to be protective against mortality . However, a nap lasting several hours  might interfere with nighttime sleep–a point which would have to be borne in mind while counseling patients regarding sleep hygiene. The ideal nap duration for adults is about 10–20 minutes and the timing depends on the quality of sleep duration the preceding night, amount of prior wakefulness and morningness-eveningness tendencies .
Prevalence and percentages of preliminary sleep diagnoses
This study’s most prevalent sleep diagnosis was chronic insomnia, followed by circadian rhythm sleep disorders. The prevalence of insomnia in the general population is 15-20%  and prevalence of circadian rhythm sleep disorders ranges from 3.1% in adults aged 40–64 to 16% in adolescents . Our prevalence of 42.6% insomnia and 20.1% CRSD is only partially comparable based on our group’s pre-selection criteria (RTx recipients having poor SQ and/or DS). Various publications suggest RTx recipients’ sleep disorders are related to medications (e.g., β-blockers , nonsteroidal anti-inflammatory drugs , corticosteroids  and mycophenolic acid ) and other clinical conditions [51, 52]. Molnar et al.  list numerous potential causes of sleep disorders in this group, including pre-existing sleep disorders, transplant surgery, hospitalization, anxiety and uncertainty, fear of organ rejection, immunosuppressive medication, deteriorating kidney function and co-morbid medical conditions, psychosocial problems, psychiatric and neurological disturbances, lifestyle, diet, environmental factors and aging. With so many possible contributing factors, the most appropriate course of action might be a referral to a sleep expert, who could counsel the patient on the full range of behavioral and medical interventions available, and help them to choose those best suited to their needs . Sleep interventions for RTx recipients are the same as for the general population, apart from the risk of interaction with immunosuppressive therapy and the need to consider the long-term side effects of their therapy (e.g., osteoporosis, new onset of diabetes, pain).
Limitation of this study
Since only 249 RTx recipients filled in the questionnaire, of which only 164 (65.9%) gave interviews, the generalizability of this study’s findings are limited. In addition, the high prevalence of RTx recipients in the “poor SQ (PSQI > 5) & and excessive DS (ESS ≥ 6)” group showing an increasing proportion along the study steps, limits the significance and comparability of the presumed sleep diagnoses.
Suggested further research
Further research will be necessary to develop safe interventions for RTx recipients with sleep-wake disturbances, taking into account their impaired renal function (limited organ survival), high risk of skin cancer (a side-effect of immunosuppressive treatment) and need to adhere to their medication regimens (high risk of acute graft rejection). These interventions should include education  regarding sleep disorders and their negative health impacts. Apart from established cognitive and behavioral interventions for insomnia, new chronotherapeutics treatments, particularly bright light therapy and melatonin supplementation  should be investigated. For RTx recipients, who already have a high number of medications to ingest daily, light therapy might be a realistic intervention to stabilize sleep-wake rhythms compared to melatonin supplementation (one more drug to ingest).