In a large cross-sectional study of HD patients from the USA and Canada, we found that sleep quality was significantly impaired. The SPI II average score in the FHN participants was 10 points higher (worse sleep quality) than scores from the general population [30
]. Furthermore, over one quarter of our sample of HD patients reported sleep quality as poor as patients with restless legs or fibromyalgia [32
]. We found that impairments in sleep quality were associated with clinically significant decrements in physical and mental well-being, vitality, and pain. We also found that worse sleep quality was significantly associated with longer recovery time from dialysis. These findings highlight the marked impairment in sleep quality among contemporary HD patients and suggest that interventions to improve sleep could have a substantial positive impact on HRQOL in this population.
We found that a higher serum phosphate concentration was associated with decrements in self-reported sleep quality independent of parathyroid hormone, comorbidities or depression. This relationship between pre-dialysis phosphorus and sleep quality is consistent with a small single-center study of a dialysis population using the SPI, which demonstrated that poor sleep quality was associated with male gender, coronary artery disease, and high serum phosphate level [5
]. Higher phosphate was independently associated with decrements in sleep quality after accounting for age, race, tobacco use, benzodiazepines, and symptoms of restless legs in an incident dialysis population [10
]. Higher serum phosphate has also been associated with impaired sleep efficiency in one study using self-reported sleep times [35
]. While the FHN Trials did not assess symptoms of pruritus, in the Dialysis Outcomes and Practice Patterns Study reporting data from 18,801 HD patients, higher serum phosphate was associated with an increased likelihood of pruritus. In another single-center study, pruritus intensity was related to sleep quality [36
]. Pruritus has also been associated with depression in the HD population [37
]. However, in our study, the association of serum phosphate with sleep quality was independent of depressive symptoms. Thus, higher serum phosphate concentrations may be a marker of other conditions, such as pruritus or cardiovascular disease, which directly cause poor sleep quality.
This study demonstrates a strong association between depression and sleep quality using validated instruments to measure both sleep quality and depression. Devins et al. [38
] demonstrated the association of depression with ‘restless sleep’ in a small sample of dialysis and kidney transplant patients. Some recent studies among patients with ESRD have demonstrated an association between poor sleep and depression, but have been limited by both small sample sizes and limited ability to adjust for potential confounders [39
]. Other recent work in the Hungarian kidney transplant and dialysis population has demonstrated significant correlations between sleep and depressive symptoms [43
]. Restless legs syndrome was associated with a high prevalence of depressive symptoms and diminished quality of life in a large sample of transplanted and waitlisted patients [44
]. Their work has also demonstrated that patient-reported restless legs syndrome, insomnia and sleep apnea were independently associated with quality of life [43
]. This report extends these previous findings by demonstrating a relationship between sleep quality rather than self-reported sleep disorders. The FHN Trials may also provide a larger and more generalizable ESRD sample than these studies which examined only waitlisted HD patients. Nonetheless, this previous work provides a potential mechanism relating sleep quality to mood and HRQOL. The strong link between sleep quality and depression should also be interpreted in light of previous findings in the general population suggesting a bidirectional relationship between sleep quality and depression. In a community sample of 7,954 respondents, the risk of developing depression was much higher in patients with sleep complaints compared to those with no sleep complaints [45
]. Insomnia has been shown to increase the risk for incident depression even after accounting for a previous history of depression [46
] and sleep symptoms were associated with depression relapse [47
]. The relationship between poor sleep quality and depression in the ESRD population is important since depression is treatable using either cognitive behavioral therapy [48
] or antidepressant medications. In addition to sleep disorders which are thought to be widely prevalent in this population [49
], worsening sleep problems should heighten the providers’ awareness for a potential depression.
The strengths of this report stem from the use of the FHN Trials which provide a large sample of patients from the USA and Canada with extensive data on comorbidity and near-perfect collection of sleep quality and HRQOL data using centrally administered surveys. The findings of this report should be interpreted in light of several limitations. This report is a cross-sectional study and is unable to discern the causal pathway for the observed relationships between poor sleep quality and both depression and hyperphosphatemia. Second, the FHN Trials uses the SPI from the Medical Outcomes Study to catalog sleep complaints in the study. The SPI II misses certain aspects of sleep such as nocturnal breathing, temperature, dreaming, and pain. However, the SPI is a widely used instrument for sleep quality and has been shown to respond to study interventions targeted toward improving sleep [51
]. Third, the FHN study does not have the indication for medication use. While previous observational studies have shown that medications such as selective serotonin reuptake inhibitors or benzodiazepines were associated with poor sleep quality [10
], the interpretation of this association is difficult since the use of medications such as antidepressants or hypnotics may be due to complaints of poor sleep quality. Fourth, the FHN Study did not collect data on a history of diagnosis of sleep apnea. However, self-reported sleep quality is an important outcome in itself and there is discordance between patient-reported sleep quality and PSG findings among both the general population and the HD patients. It would be important in future HD studies to include both patient-reported and objective measures of sleep disorders using polysomnography or sleep apnea monitors.
Poor sleep is common and extremely bothersome to HD patients and among the primary reasons for considering more intensive HD therapies. Since sleep quality is strongly associated with quality of life and time to recovery from dialysis, these findings underscore the link between sleep and daytime function and support the position that improving sleep may provide an important opportunity to improve outcomes in ESRD. As previously noted, there is a need for treatment trials for poor sleep in ESRD [52
]. We have identified several factors associated with poor sleep – elevated serum phosphate concentrations and depressive symptoms. It will be important in future work to understand the relationships between sleep quality, serum phosphorus control, depression, and HRQOL among those randomized to the frequent dialysis arm compared to the standard arm of FHN Daily. Future studies, including results of the FHN Trials, may provide insight into whether favorable modification of these factors might improve sleep quality and HRQOL.