Sleep disturbance among Malaysian patients with end-stage renal disease with pruritus

Chronic kidney disease associated-pruritus (CKD-aP) is a well-recognized, frequent and compromising complication among patients on hemodialysis. Treating CKD-P is a huge challenge [1, 2]. Treatment is difficult due to the refractory nature of the disease [3]. The absence of suitable and effective treatments for CKD-aP management has resulted in poor sleep among hemodialysis patients [3]. The prevalence of CKD-aP varies from country to country. This may be due to advancement in basic health and medical sciences in developed countries versus developing countries [4]. The prevalence of CKD-aP has decreased from 90% [5] in the 1970s to 22–55% in the modern era [6‐8].

The pathophysiology of CKD-aP is not completely clear [1] and is believed to be multifactorial, resulting from the integration of multiple factors’ including demographics, neuropathic and psychogenic factors [9]. During hemodialysis, numerous cytokines including interleukin-1 are released following contact with plasma and the dialysis membranes [10]. Interleukin-1 has been suggested to stimulate the release of possible pruritogenic substances [11]. It is also suggested that in hemodialysis patients, accumulation of non-dialyzable middle molecules stimulate free nerve endings contributing to pruritus [11].

CKD-aP usually begins about six months after the start of dialysis [12], and studies have shown a significant positive relationship between pruritus and the duration of hemodialysis [13]. Pruritus can present as either an acute or chronic condition [7], either generalized or localized; and may last from a few months to in some cases more than one year [14]. The onset of pruritus, its duration, and its intensity can change over time, and itch has been reported to worsen at night [15]. The body parts affected are the back, limbs, chest, and head [15].

Pruritus is an undesirable situation that aggravates itchiness and negatively affects patients’ sleep as well as the quality of life [16, 17] as it causes nocturnal awakenings and creates difficulty in falling asleep [18, 19]. A higher mortality risk is also observed in those with poor sleep quality [20]. Moderate to extreme CKD-aP had 15–21% higher mortality compared to those without pruritus [15]. Therefore, the aim of this study was to estimate the prevalence of CKD-aP among hemodialysis patients in Malaysia, to determine the impact of CKD-aP on sleep quality and any factors associated with CKD-aP.

A cross-sectional, multi-centered study was conducted from February to September 2017 at a tertiary hospital and its affiliated dialysis centers in Kuala Lumpur, Malaysia.

A total of 334/334 patients were recruited (response rate = 100%). The flow on how patients were recruited is shown in Fig. 1. The majority were male (59.6%) and Chinese (61.7%). Significantly more Malays had pruritus (p = 0.014). The duration of having CKD and duration in months receiving dialysis were significantly higher in patients with pruritus. Hypertension (n = 142), diabetes mellitus (n = 85), and hyperlipidemia (n = 30) were the most common co-morbidities observed in CKD patients with pruritus (Table 1).

The prevalence of CKD-aP was high, of which the majority of patients reported that it was mild in severity. The intensity of pruritus was significantly associated with poorer sleep quality.

The prevalence of CKD-aP in our study was 61.3%, which was similar to previous studies in Malaysia which reported rates of 58.6% [27] and 64.2% [28]; Turkey (53.4 and 85.4%) [29, 30] and74% in Pakistan [31]. The possible reasons for the variation in the prevalence of CKD-aP among different studies may be due to the study design, cohort studied (sample size, different study population), ethnicity (i.e. the individual’s tolerance or threshold for itch) or instruments used to assess CKD-aP [4, 32]. Moreover, the assessment of pruritus is also subjective one as it is based on perception, which is influenced by cultural, educational and socio-economic status [32]. Patients with depressive symptoms were reported to have 1.3 to 1.7 times higher risk of developing severe pruritus compared to those without depression [15, 33]. Patients with increased pruritus severity were also found to be more likely to miss hemodialysis sessions. Missed hemodialysis sessions have been associated with increased all-cause, cardiac-related, and infection-related hospitalizations and mortality [34].

The prevalence of CKD-aP in our study was 61.3%. However, the majority (86.3%) reported that their pruritus was mild. Our findings differed from previous studies which reported prevalence rates of mild pruritus as 48.8% in Japan [35], 22.2% in Egypt [36], and 41.7% in Saudi Arabia [37]. In our setting, only high-flux dialyzers were used, and studies have shown that high-flux dialyzers efficiently remove average-sized molecules associated with the aggravation of pruritus better than low-flux dialyzers [38]. However, some studies reported a high prevalence of CKD-aP even when patients were on high flux dialyzers: 62.6% in Taiwan [39], 53.4% in Turkey [30], 72.9% in Japan [38], 74.3% in Israel [40]. This may be due to the different type of dialyzer membranes used. Patients on dialyzers which uses polysulphone membranes experienced more pruritus than those using haemophane or cuprophane membranes [13, 41]. Some pruritogenic substances may be activated or released in greater amounts after blood contact with polysulphone membranes compared to other materials [42]. Use of high-flux polyacrylonitrile membrane has been reported to alleviate the severity of pruritus [43]. Hemodialysis with the target of Kt/V ≥ 1.5 (K = dialyzer clearance of urea, t = dialysis time, V = volume of distribution of urea, approximately equal to patient’s total body water) [44], as well as the use of high-flux dialyzer, may play a role in reducing the severity of uremic pruritus [44‐46]. A search of published literature found that other factors that were found to be associated with CKD-aP were elevated blood urea nitrogen (BUN) [38, 47, 48]; crystal deposition of calcium and phosphate on skin (due to hypercalcemia and hyperphosphatemia) [49]; high aluminum level [50]; secondary hyperparathyroidism [47]; erythropoietin deficiency, high ferritin level, lower transferrin [30] and xerosis [51]. However, we did not found any associations in our study.

In our study, 48.8% of patients reported occasional delays in falling asleep, followed by 9.8% with frequent delays in falling asleep affected due to CKD-aP. Our findings were similar with other studies, where more than 45% [15], 59.1% [52] and 70% [38] of patients suffering from moderate to severe CKD-aP were observed to have poor sleep quality. Patients with moderate to severe pruritus were found to be 5.47 times more likely to exhibit bad sleep as compared to patients with mild pruritus, which was lower than a previous study which reported an odds ratio of 8.4 times for poor sleep [1]. A possible reason may be due to the fact that the majority of our patients reported having mild pruritus as opposed to having moderate or severe pruritus [53].

A limitation of our study was that the data collected was not generalizable, as it was only collected from dialysis centers based in Kuala Lumpur. We also did not have an (age and sex-matched) control group for our population. However, the strength of our study was that we had a very good response rate.

In Malaysia, the prevalence of CKD-aP was 61.3%, of which the pruritus experienced was mild. Patients with moderate to severe pruritus were found to be 5.47 times more likely to experience poor sleep quality as compared to patients with mild or no pruritus.