Effect of vitamin D on sleep quality in hemodialysis patients

1Department of Adult Nephrology, School of Medicine, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2Department of Internal Medicine, School of Medicine, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3Department of Endocrinology, School of Medicine, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran


Introduction
Sleep disorder is commonly experienced by hemodialysis (HD) patients. Previous studies showed that about 50%-80% of HD patients suffered from sleep disorders (dyssomnia) (1)(2)(3). These disorders consist of insomnia (problems in the start of sleeping and/or repeated waking in the nights) and feeling sleepy during the daytime, restless legs syndrome and/or periodical limb movements and sleep apnea (1,4). Sleep quality significantly contributes to the improvement of life quality (2,5,6). Sleep disorders are associated with impairment in immune functioning (1,7), increased mortality and cardiovascular risk (2,5,6). There is an association between sleep quality of HD patients and the following factors; female gender, older age, caffeine consumption, alcohol consumption, tobacco abuse, concurrent comorbidity, recombinant erythropoietin therapies, years receiving dialysis, dialysis shift, depression, physical performance, greater body mass index (BMI) values, dialysis efficiency, anemia, hypoalbuminemia, parathyroid hormone and serum creatinine (8)(9)(10). Deficiency of vitamin D is commonly experienced by patients who undergo dialysis (6,11,12). Several studies reported the relationship of vitamin D deficiency and sleep disorders in non-dialysis (13,14) and dialysis patients (6,15). Also, according to several research works, vitamin D deficiency treatment improves sleep quality in non-dialysis patients (16,17).

Objectives
The present study aims at determining the effect of vitamin D deficiency treatment on the sleep quality of patients receiving HD.

Study population
This clinical trial was conducted at HD center of Loghman Hakim hospital in Tehran, Iran from May 2018 to June 2019. The inclusion criteria were the following; being above 18 years, receiving dialysis for a minimum of three months, HD adequacy (Kt/V>1/2), 25-hydroxy vitamin D (25(OH)D) <30 ng/mL, and Pittsburgh Sleep Quality Index (PSQI) ≥5. Psychiatric disorders (clinical diagnosis and or previous treatment), drug abuse, alcohol consumption, smoking, habits such as having coffee or tea prior to sleep and any hospitalization record during the previous four weeks were considered as the exclusion criteria.
First, the serum level of vitamin D was measured by enzyme-linked immunosorbent assay (ELISA) in the morning venous blood sample. Then, we completed the Pittsburg Sleep Quality questionnaire for patients with vitamin D deficiency. Out of 200 HD patients, only 30 individuals met the inclusion criteria ( Figure 1). We employed the PSQI to collect information through selfreports to determine the quality as well as the quantity of sleep during one month before assessment. PSQI consists of 19 individual items, which create seven components of subjective sleep quality, sleep latency, length of sleep, habitual sleep efficiency, sleep disturbance, taking sleep medicine and dysfunctions during the day, which provide one global score between 0-21. Scores of five or higher suggested a poorer sleep. This questionnaire has validity and reliability (18). Because of vitamin D deficiency complications in people receiving HD and its ethical considerations, all patients with vitamin D deficiency were treated. Confounding factors were controlled too. Treatment was performed using 50 000 units of vitamin D 3/week over a 12-week interval. Measurement of the serum 25(OH)D levels as well as PSQI scores was carried out following the treatment. Patients were revisited and excluded if they met exclusion criteria after 12 weeks, although all patients remain in the trial.

Statistical analysis
Data were analyzed by SPSS 24, while data distribution was considered using paired t test. Mean ± SD or median was used to show the study results regarding normal or non-normal distribution of continuous variables along with numbers or percentages for the nominal variables. P value of <0.05 was set as the significance level. Table 1 presents baseline demographics. Research participants included 19 males and 11 females. The age distribution was between 32 and 85 years, with a mean age of 56.7 ± 14.31 years. Etiologic findings of ESRD indicated diabetes in 12 (40%) and hypertension in 8 (26.7%) patients. The mean of the duration of HD was 42.20 ± 40.28 months. The participants' mean of vitamin D level was 18.61 ± 6.32 ng/mL before treatment and 41.14 ± 9.62 ng/mL after treatment. A mean PSQI score of 9.97 was obtained at week 0 while it was 9.47 (mean difference 0.005) after 12 weeks that did not show statistical significance (P = 0.473).

Results
Habitual sleep efficiency significantly changed after treatment (P = 0.037), meaning that the number of hours slept/number hours spent in bed increased ( Table 2).

Discussion
Based on our study, PSQI score did not change significantly after the treatment of vitamin D deficiency. Prior literature indicates the relationship of vitamin D deficiency with the quality of sleep in dialysis patients, but no study has been performed on the treatment of vitamin D deficiency in HD patients.
Hon et al and Yavuz et al approved that the levels of 25(OH) D fell down in dialysis patients having sleep disturbances, in comparison with those that do not have sleep disorders (6,15). However, they did not confirm whether the treatment of vitamin D deficiency could affect the quality of sleep. Improvement of sleep quality with vitamin D supplement was reported in some studies. Gominak et al showed sleep improvement with 25(OH) D supplement in individuals who suffer neurologic problems and had evidence of abnormal sleep; however, only a limited range of 25(OH)D blood level of 60-80 ng/mL was maintained (16). This level of vitamin D is not recommended in dialysis patients, therefore we kept vitamin D level between 30-40 ng/mL, according to other studies. In another study, which was conducted on patients with chronic pain, sleep latency, sleep duration and global PSQI score improved with 25(OH)D supplement (17).
Sahakyan reported insomnia improvement with a combination of vitamin D and melatonin in 60-65-yearold women with vitamin D deficiency (19).
The difference of our study is that most studies were carried out on non-HD people. The second reason may be other confounding factors not yet found. The small number of participants may also be the other reason for this difference.
Kidir et al examined the effect of vitamin D on sexual dysfunction in 37 dialysis patients (40.5% HD patients and 59.5% peritoneal dialysis patients). They measured several parameters including sleep disorders and sleep score, and found that vitamin D treatment for 6 months did not affect sleep score (20).
Vitamin D deficiency has many complications in dialysis patients, hence all these patients must be treated.

Conclusion
Treatment of vitamin D deficiency does not affect the quality of sleep according to PSQI in HD patients. However, habitual sleep efficiency significantly changed after treatment.

Limitations of the study
The subjective nature of the PSQI could lead to limitations on its value in cases where some patients did not cooperate well. Moreover, another limitation was the small sample size of our study.