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International Journal of Pediatrics and Adolescent Medicine (2016) xx, 1e7

H O S T E D BY Available online at www.sciencedirect.com 61

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journal homepage: http://www.elsevier.com/locate/ijpam 67
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9 ORIGINAL RESEARCH ARTICLE 71
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12 Sleep disorders in children with chronic 73
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14 kidney disease 75
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A.H. Darwish a,*, H.H. Abdel-Nabi b 78
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Pediatric Department, Pediatric Neurology Unit, Tanta University Hospital, Faculty of Medicine, 81
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Q2 Tanta University, Egypt 82
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Pediatric Department, Pediatric Nephrology Unit, Tanta University Hospital, Faculty of Medicine, 83
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Tanta University, Egypt 84
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Received 19 April 2016; received in revised form 30 May 2016; accepted 7 June 2016 86
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29 KEYWORDS Abstract Objectives: This case-control study assessed the prevalence of sleep disorders 91
30 among Egyptian children with chronic kidney disease (CKD), either maintained or not main-
CKD-not on dialysis; 92
31 tained on hemodialysis (HD), and compared them with healthy age and sex-matched children.
CKD-on dialysis 93
32 Patients and methods: The total study population included 95 children, 54 of whom were CKD
children; 94
33 patients, 22 maintained on HD and 32 not maintained on HD; 41 healthy children of matched
Sleep disorders; 95
34 Q3 age and sex composed the control group.
Restless-leg syndrome 96
35 Subjective impairment of sleep quality was assessed using the Arabic version of the Chil- 97
36 dren’s Sleep Habits Questionnaire (CSHQ). Daytime sleepiness and restless leg syndrome 98
37 (RLS) were assessed using a pediatric modification of the Epworth sleepiness scale (ESS) and 99
38 RLS Questionnaire, respectively. 100
39 Results: Sleep disturbances were detected in 75.9% of the studied children with CKD: 81.8% in 101
40 children with CKD undergoing dialysis, and 71.8% in children with CKD not on dialysis. Excessive 102
41 daytime sleepiness (EDS) and RLS symptoms were reported in 22% and 20.4% of the studied chil- 103
42 dren with CKD, respectively. 104
43 Conclusions: Sleep disturbances are very common among children with CKD. Sleep distur- 105
44 bances in patients with CKD include restless legs syndrome (RLS), excessive daytime sleepiness 106
45 (EDS), sleep-disordered breathing (SDB), behavioral insomnias and parasomnias. 107
46 Copyright ª 2016, King Faisal Specialist Hospital & Research Centre (General Organization), 108
47 Saudi Arabia. Production and hosting by Elsevier B.V. This is an open access article under 109
48 the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 110
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53 Abbreviations: CKD, chronic kidney disease; HD, Hemodialysis; eGFR, estimated glomerular filtration rate; CSHQ, Children’s Sleep Habits
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54 Questionnaire; ESS, Epworth sleepiness scale; EDS, Excessive daytime sleepiness; RLS, restless leg syndrome; BMI, body mass index; ESRD,
End stage renal disease; Hb, Hemoglobin; Ca, Total serum calcium; P, Serum phosphorus; SDB, sleep-disordered breathing. 116
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* Corresponding author. 117
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E-mail addresses: dradarwish2012@gmail.com (A.H. Darwish), hendabdelnabi@yahoo.com (H.H. Abdel-Nabi). 118
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Peer review under responsibility of King Faisal Specialist Hospital & Research Centre (General Organization), Saudi Arabia. 119
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http://dx.doi.org/10.1016/j.ijpam.2016.06.001 121
60 2352-6467/Copyright ª 2016, King Faisal Specialist Hospital & Research Centre (General Organization), Saudi Arabia. Production and hosting 122
by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: Darwish AH, Abdel-Nabi HH, Sleep disorders in children with chronic kidney disease, International
Journal of Pediatrics and Adolescent Medicine (2016), http://dx.doi.org/10.1016/j.ijpam.2016.06.001
 IJPAM79_proof ■ 29 June 2016 ■ 2/7

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2 A.H. Darwish, H.H. Abdel-Nabi

1 1. Introduction The Total Sleep Disturbance score included all of the 63

2 items from the eight subscales; the parents were asked to 64
3 An adequate amount and quality of sleep are essential for recall sleep behaviors occurring over a “typical” recent 65
4 normal growth, development and overall health of chil- week. Items were rated on a three-point scale: “usually” if 66
5 dren. Disturbed sleep can adversely affect a child’s daytime the sleep behavior occurred 5e7 times/week, “sometimes” 67
6 function, resulting in behavioral and emotional problems as 2e4 times/week and “rarely” for zero to one time/week. 68
7 well as decrements in daytime alertness and cognitive Each question was scored from 1 to 3, (one being rarely, 2 69
8 performance [1]. being sometimes, and 3 being usually) and then summed to 70
9 Sleep disorders are an important but often overlooked create a total sleep score (with the total ranging from 33 to 71
10 health problem in children with chronic kidney disease 99). Some items were reversed to make a higher score 72
11 (CKD) [2]. To date, a small number of studies have focused indicative of more disturbed sleep. Higher scores indicated 73
12 on sleep disturbances in children with CKD. Additionally, a poorer quality of sleep. A total sleep score of 41 on the 74
13 the underlying mechanisms of sleep problems in CKD CSHQ is reported as the clinical cutoff for the identification 75
14 remain unclear. The aim of this study was to assess the of probable sleep problems [5]. 76
15 prevalence and risk factors of sleep disorders among A pediatric modification of the Epworth sleepiness scale 77
16 Egyptian children with chronic kidney disease (CKD), either (ESS) was used to assess daytime sleepiness, in which sub- 78
17 maintained or not maintained on hemodialysis (HD), and to jects were asked to rate, on a scale of 0e3, how likely they 79
18 compare them with healthy children. would be to fall asleep in eight situations [8]. Excessive 80
19 daytime sleepiness (EDS) was defined as an ESS score  11. 81
20 The restless leg syndrome (RLS) Questionnaire, derived 82
21
2. Patients and methods from the standard criteria for the diagnosis of RLS in chil- 83
22 dren and adolescents [9], was administered to determine 84
23 The study was approved by the Institutional Review Board the prevalence of RLS. Patients were given a positive 85
24 of Faculty of Medicine, Tanta University, and informed diagnosis of RLS if they had a positive response to four 86
25 consent was obtained from all participants prior to standard questions: (1) an urge to move due to uncom- 87
26 inclusion. fortable sensations in the legs, (2) uncomfortable sensa- 88
27 The total study population included 95 patients, 54 of tions that are relieved by movement, (3) symptoms worsen 89
28 whom were CKD patients; 22 patients were maintained on during rest or inactivity, and (4) symptoms worsen in the 90
29 HD, and 32 patients were not maintained on HD. Another 41 evening. The questionnaire was filled out by the parent in 91
30 healthy children of matched age and sex served as the the presence of the child for children aged 6e12 years and 92
31 control group. Participants were recruited from the independently by older children and adolescents. 93
32 outpatient nephrology clinic and hemodialysis unit in the 94
33 Department of Pediatrics, Faculty of Medicine, Tanta Uni- 2.1. Statistical analysis 95
34 versity Hospital, AlGharbia, Egypt from June 2014 to 96
September 2015.
35 Descriptive statistics were calculated as the mean  SD for 97
36 Children younger than 6 years of age were excluded, as 98
continuous variables and as numbers and percentages for
37 they could not reliably comprehend the questionnaire 99
categorical variables using SPSS V.16. Group differences
38 about RLS. Children on sedative or hypnotic medications or 100
were tested using the chi-square test for categorical vari-
39 suffering from any other chronic illness were also excluded. 101
ables and one-way ANOVA for continuous variables. ANOVA
40 The stages of CKD were determined based on the eGFR 102
was followed by a Tukey HSD (Honestly Significant Differ-
41 using the Schwartz formula [3]. 103
ence) post hoc test. Correlation coefficients and linear and
42 National Kidney Foundation Disease Outcomes Quality 104
Q5
logistic regression models were used to evaluate the asso-
43 Initiative (K/DOQI) CKD stages: [4] 105
ciation between sleep disturbance and variables such as
44 age, BMI, and eGFR. All tests were two-sided, and differ- 106
45 1. Stage 1: eGFR  90 mL/min/1.73 m2 ences were considered to be significant at P < .05. 107
46 2. Stage 2: eGFR Z 60e89 mL/min/1.73 m2 108
47 3. Stage 3: eGFR Z 30e59 mL/min/1.73 m2 109
4. Stage 4: eGFR Z 15e29 mL/min/1.73 m2 3. Results
48 110
49 5. Stage 5: eGFR < 15 mL/min/1.73 m2, or receiving 111
50 dialysis. Studied groups’ characteristics and demographic data are 112
51 presented in Table 1. The total study population included 113
52 Subjective impairment of sleep quality was assessed 95 patients, with 54 CKD patients, 22 patients maintained 114
53 using the Children’s Sleep Habits Questionnaire (CSHQ) [5]. on HD (n 22; M/F 12:10) and 32 CKD patients not maintained 115
54 The children’s mothers completed the Arabic version of the on HD (n 32; M/F 19:13); 41 healthy children of matched 116
55 CSHQ [6]. The CSHQ was translated, modified and validated age and sex served as a control group (n 41; M/F 23:18). End 117
56 for this population and culture. It is a retrospective, 33- stage renal disease (ESRD) patients were undergoing regular 118
57 item parent questionnaire grouped into eight subscales HD three times/week for 3e4 h using bicarbonate dialysis 119
58 reflecting the following sleep domains: bedtime resistance to maintain a minimum Kt/V index of 1.2 per session. 120
59 (5 items), sleep onset delay (1 item), sleep duration (3 The studied groups’ laboratory data are presented in 121
60 items), sleep anxiety (3 items), night waking (3 items), Table 2. Serum creatinine, hemoglobin, calcium, and 122
61 parasomnias (7 items), sleep-disordered breathing (3 phosphorus were significantly higher in CKD children on 123
62 items), and daytime sleepiness (8 items) [7]. hemodialysis compared to nonedialysis-dependent CKD 124

Please cite this article in press as: Darwish AH, Abdel-Nabi HH, Sleep disorders in children with chronic kidney disease, International
Journal of Pediatrics and Adolescent Medicine (2016), http://dx.doi.org/10.1016/j.ijpam.2016.06.001
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Q1
Sleep disorders in children 3

1 63
Table 1 Studied groups’ characteristics and demographic data.
2 64
3 Parameters Group 1 Group 2 Group 3 P value 65
4 CKD-dialysis patients CKD-non-dialysis patients Healthy controls 66
5 Number 22 32 41 67
6 Sex (Male/Female) 12/10 19/13 23/18 .86 68
7 Male (%) 54.5 59.3 56.1 69
8 Age (years) Mean (SD) 10.70 (2.83) 9.31 (2.71) 9.64 (3.43) .25 70
9 Weight (kg) Mean (SD) 26.93 (11.64) 29.87 (9.66) 33.26 (13.03) .20 71
10 BMI Mean (SD) 16.83 (3.44) 18.68 (2.99) 19.15 (3.62) .24 72
11 Height (cm) Mean (SD) 124.60 (17.68) 126.30 129.27 (16.83) .36 73
12 (14.45) 74
13 Estimated GFR (ml/min/1.73 m2) Mean (SD) 10.69 (2.33) 82.08 (17.83) 103.80 (8.07) <.001 75
14 Duration of HD (months) Mean (SD) 26.77 (25.87) 76
15 Kt/V Mean (SD) 1.13 (0.085) 77
16 78
CKD: Chronic kidney disease, BMI: Body mass index, GFR: Glomerular filtration rate, HD: Hemodialysis.
17 79
18 80
19 81
20 Table 2 Studied groups’ laboratory data. 82
21 83
Parameters Group 1 Group 2 Group 3 P value
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CKD-dialysis patients CKD-non-dialysis patients Healthy controls
23 85
24 Creatinine (mg/dL) Mean (SD) 5.92 (1.16) 0.97 (0.19) 0.64 (0.12) <.001 86
25 Hemoglobin (g/dL) Mean (SD) 10.45 (1.44) 11.26 (0.87) 12.00 (0.81) <.001 87
26 Total Ca (mg/dL) Mean (SD) 9.65 (0.89) 10.17 (0.57) 10.41 (0.46) <.001 88
27 P (mg/dL) Mean (SD) 5.35 (0.75) 4.29 (0.47) 4.33 (0.59) <.001 89
28 Ca: Total serum calcium, P: Serum phosphorus. 90
29 91
30 92
31 children and controls (P < .05). However, there was no 93
32 significant difference between nonedialysis-dependent 94
33 CKD children and controls (P > .05). 95
34 Figs. 1 and 2 show the causes of CKD in the studied 96
35 children. Glomerulonephritis was the most common cause, 97
36 accounting for 45.4% in dialysis-dependent and 68.7% in 98
37 non-dialysis-dependent children with CKD. Fig. 3 displays 99
38 the stages of CKD in non-dialysis-dependent CKD patients; 100
39 62.5% of the studied non-dialysis-dependent CKD patients 101
40 had Stage 2 disease. 102
41 The Children’s Sleep Habits Questionnaire (CSHQ) total 103
42 and subscale scores are presented in Table 3. The total 104
CSHQ scores were significantly higher in both groups of CKD Figure 2 Causes of CKD in non-dialysis patients.
43 105
44 children compared to controls (P < .05), while no significant 106
45 difference was observed between CKD children on hemo- 107
46 dialysis and nonedialysis-dependent patients (P Z .054). 108
47 109
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62 Figure 1 Causes of CKD in dialysis patients. Figure 3 Stages of CKD in non-dialysis patients. 124

Please cite this article in press as: Darwish AH, Abdel-Nabi HH, Sleep disorders in children with chronic kidney disease, International
Journal of Pediatrics and Adolescent Medicine (2016), http://dx.doi.org/10.1016/j.ijpam.2016.06.001
 IJPAM79_proof ■ 29 June 2016 ■ 4/7

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4 A.H. Darwish, H.H. Abdel-Nabi

1 63
Table 3 The Children’s Sleep Habits Questionnaire (CSHQ): total and subscales scores in the studied groups.
2 64
3 CSHQ subscales scores Group 1 Group 2 Group 3 P value 65
4 (Rang, mean(SD) CKD-dialysis patients CKD-non-dialysis patients Healthy controls 66
5 1. Bedtime resistance 6e14 6e12 6e8 <.001 67
6 9.45 (2.06) 8.06 (2.29) 6.02 (0.93) 68
7 2. Sleep onset delay 1e3 1e3 1e2 <.001 69
8 2.45 (0.59) 1.5 (0.56) 1.14 (0.35) 70
9 3. Sleep anxiety 4e9 4e7 4e6 <.001 71
10 5.31 (1.76) 5.12 (1.38) 3.78 (0.68) 72
11 4. Sleep duration 3e8 4e7 3e6 <.001 73
12 5.4 (1.4) 5.12 (0.83) 4.04 (0.86) 74
13 5. Night waking 3e7 3e6 3e5 <.001 75
14 5.03 (1.37) 4.27 (0.98) 4.0 (0.77) 76
15 6. Parasomnias 7e16 7e13 7e10 <.001 77
16 11.40 (2.51) 9.65 (1.71) 8.41 (0.77) 78
17 7. Sleep-disordered breathing 3e6 3e4 3e4 .036 79
18 4.2 (0.71) 3.53 (0.50) 3.31 (0.47) 80
19 8. Daytime sleepiness 10e22 8e15 8e12 <.001 81
20 14.77 (3.95) 10.93 (1.91) 8.97 (0.93) 82
21 CSHQ Total scores 41e78 35e64 34e48 <.001 83
22 54.81 (9.45) 50.18 (7.98) 39.70 (4.31) 84
23 CSHQ score >41 18 (81.8%) 23 (71.8%) 8 (19.5%) <.001 85
24 (n %) 86
25 87
26 88
27 89
28 Table 4 The Epworth sleepiness scale (ESS) scores of the studied groups. Q4 90
29 91
ESS scores Group 1 Group 2 Group 3 P value
30 92
CKD-dialysis patients CKD-non-dialysis patients Healthy controls
31 93
32 Range 5e18 3e14 2e14 94
33 Mean (SD) 11.72 (3.48) 7.25 (2.67) 5.07 (2.47) <.001 95
34 ESS score  11 96
35 (n %) 10 (45.5%) 2 (6.25%) 1 (2.4%) <.001 97
36 Total n 22 32 41 98
37 99
38 100
39 101
40 102
41 Table 5 Restless legs syndrome (RLS) symptoms in the studied groups. 103
42 104
RLS (n %) Group 1 Group 2 Group 3 P value
43 105
CKD-dialysis patients CKD-non-dialysis patients Healthy controls
44 106
45 Yes 8 (36.4%) 3 (9.4%) 1 (2.4%) 107
46 No 14 (63.6) 29 (90.6%) 40 (97.6%) <.001 108
47 Total 22 32 41 109
48 110
49 111
50 Approximately 75.9% of the studied children with CKD nonedialysis-dependent CKD children (P < .05), while both 112
51 scored above the CSHQ clinical cutoff score for disordered groups of children with CKD had scores significantly higher 113
52 sleep: 81.8% in dialysis patients and 71.8% in non-dialysis than controls (P < .05). Sleep-disordered breathing and 114
53 patients. night waking were significantly higher in CKD children on 115
54 The sleep duration and sleep anxiety scores on the CSHQ hemodialysis compared to nonedialysis-dependent CKD 116
55 were significantly higher in both groups of CKD children children and controls (P < .05). However, no significant 117
56 compared to controls (P < .05), while no significant dif- difference was observed between nonedialysis-dependent 118
57 ference was observed between CKD children on hemodial- CKD children and controls (P > .05). 119
58 ysis and nonedialysis-dependent CKD patients (P > .05). The Epworth sleepiness scale (ESS) results of the studied 120
59 The subscale scores of bedtime resistance, sleep onset groups are presented in Table 4. The ESS score was signif- 121
60 delay, daytime sleepiness and parasomnia were signifi- icantly higher in CKD children on hemodialysis compared to 122
61 cantly higher in CKD children on hemodialysis than in those not on dialysis (P < .05). Both groups of CKD children 123
62 124

Please cite this article in press as: Darwish AH, Abdel-Nabi HH, Sleep disorders in children with chronic kidney disease, International
Journal of Pediatrics and Adolescent Medicine (2016), http://dx.doi.org/10.1016/j.ijpam.2016.06.001
 IJPAM79_proof ■ 29 June 2016 ■ 5/7

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Sleep disorders in children 5

1 had ESS scores that were significantly higher than those of The high prevalence of sleep disturbances in our study is 63
2 controls (P < .05). An ESS score 11 was reported in 22% of similar to that reported in previous studies among children 64
3 the studied children with CKD: 45.5% in dialysis patients with CKD; sleep disorders were reported in 32%e85% of 65
4 and 6.25% in non-dialysis patients compared to 2.4% of the children with CKD [10e14]: 77e85% in dialysis pa- 66
5 children in the control group. EDS was significantly more tients [10,11,14], and 32e50% in non-dialysis patients 67
6 prevalent in the in dialysis patients (P < .001). [11e13]. 68
7 The RLS symptoms in the studied groups are presented in Sleep disturbances detected in our patients with CKD 69
8 Table 5. RLS symptoms were reported in 20.4% of the included RLS, EDS, sleep-disordered breathing (SDB), 70
9 studied children with CKD: 36.4% in dialysis patients and behavioral insomnias and parasomnias. Bedtime resistance, 71
10 9.4% in non-dialysis patients. RLS symptoms were reported sleep onset delay, daytime sleepiness and parasomnia were 72
11 in only 2.4% of the children in the control group. The more reported in hemodialysis-dependent than non- 73
12 prevalence of RLS was significantly higher in the in dialysis dialysis-dependent CKD children; both groups had higher 74
13 patients (P < .001). scores than the control group. Children with CKD displayed 75
14 more sleep anxiety and shorter sleep duration than normal 76
15 3.1. The association between sleep disorders and children, with no difference between hemodialysis and 77
16 demographic and laboratory data in children with nonedialysis-dependent CKD children. 78
17 CKD We observed SDB and night waking in HD patients, but 79
18 not in nonedialysis-dependent CKD children. Both pediatric 80
19 There was a significant negative correlation between CSHQ and adult studies have shown that SDB is common among 81
20 scores and eGFR (r Z 0.28, P Z .04) and Ca (r Z 0.384, advanced CKD (stages 4e5) and HD patients [10,11,14e16]. 82
21 P Z .004), with no significant correlation between the The non-dialysis-dependent CKD children in our study did 83
22 score and age (r Z 0.7, P Z .5), BMI (r Z 0.158, not include stage IV CKD because of the lack of a trans- 84
23 P Z .125), or Hb (r Z 0.23, P Z .089). There was a sig- plantation program at Tanta University Hospital; therefore, 85
24 nificant positive correlation between serum phosphorus most stage IV CKD patients are followed in other centers for 86
25 (r Z 0.52, P < .001) and CSHQ scores. preemptive transplantation. Furthermore, stage III CKD was 87
26 Linear regression revealed a significant positive associ- observed in only 12.5% of non-dialysis-dependent children, 88
27 ation between the serum phosphorus and CSHQ scores; which may explain why SDB was not reported in our pa- 89
28 every increase in serum P by 1 mg/dL was associated with tients with non-dialysis-dependent CKD. Similarly, Sinha 90
29 an increase in CSHQ scores by 6.865. A significant negative et al [12] reported SDB in only 6% of nonedialysis-depen- 91
30 association between the GFR and CSHQ scores and a dent CKD children; most of the children studied were stage 92
31 decrease in GFR by 10 ml/min/1.73 m2 were associated 1 and 2, while stage 4 was observed in only 2%. 93
32 with an increase in CSHQ scores by 0.65. Linear regression We reported EDS in 22% of the studied children with CKD, 94
33 revealed no significant association between CSHQ and age, with a prevalence of 45.5% in dialysis patients and 6.25% in 95
34 BMI, Hb, or Ca. non-dialysis patients. EDS was reported in only 2.4% of the 96
35 There was a significant positive correlation between the children in the control group. RLS symptoms were detected 97
36 ESS score and serum P (r Z 0.6, P < .001) and serum in 20.4% of the studied children with CKD: 36.4% in dialysis 98
37 creatinine (r Z 0.555, P < .001), with a significant negative patients and 9.4% in non-dialysis patients. RLS symptoms 99
38 correlation between the ESS score and GFR (r Z 0.659, were reported in only 2.4% of the control group. 100
39 P < .001), with no significant correlation between the ESS Our findings are consistent with those of previous studies 101
40 score and age, Hb or BMI. Linear regression revealed a among children with CKD; EDS symptoms were reported in 102
41 significant negative association between GFR and ESS. 29e60% of children with CKD: 60% ln dialysis patients 103
42 Every decrease in GFR by 1 ml/min/1.73 m2 was associated [10,11,14] and 29e39.7% in non-dialysis patients [11,17]. 104
43 with an increase of 0.079 in ESS. Linear regression revealed RLS symptoms were reported in 10%e35% of children with 105
44 no significant association between ESS and age, Hb, BMI, or CKD [14,17,18]. 106
45 serum phosphorus. The prevalence of sleep disorders among adults with 107
46 Logistic regression revealed a significant negative asso- CKD ranges from 40% to 80% [19e21], and RLS symptoms are 108
47 ciation between GFR and RLS (P < .05); a decrease in GFR reported in 20%e40% of adult patients with CKD [22e24]. 109
48 by 1 ml/min/1.73 m2 was associated with an increase in the The variation in prevalence of sleep disturbances in 110
49 probability of RLS by 49%. No association was observed children with CKD between the studies is likely due to 111
50 between RLS and other variables, e.g., age, Hb, serum Ca, different populations being studied, either dialysis- 112
51 or serum phosphorus. dependent or non-dialysis-dependent; differences be- 113
52 tween the number of studied subjects; the method of 114
53 diagnosis of sleep disorders, whether based on question- 115
54 4. Discussion naires or polysomnography (PSG); and the type of ques- 116
55 tionnaire used to assess sleep disturbances. Sinha et al [12] 117
56 In the present study, symptoms of sleep disturbances were and Roumelioti et al [13] reported disordered sleep in 37% 118
57 detected in 75.9% of the studied children with CKD and in and 12% of the studied CKD children, respectively. The 119
58 19.5% of the normal children in the control group. Sleep lower prevalence of sleep problems in these studies may be 120
59 disturbances were more frequent in the hemodialysis group related to under-detection of sleep problems due to not 121
60 compared with non-dialysis CKD patients, with a prevalence using validated sleep questionnaires. In addition, those 122
61 of 81.8% in hemodialysis patients and 71.8% in non-dialysis authors studied only non-dialysis-dependent CKD children 123
62 patients. and did not include dialysis patients. 124

Please cite this article in press as: Darwish AH, Abdel-Nabi HH, Sleep disorders in children with chronic kidney disease, International
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6 A.H. Darwish, H.H. Abdel-Nabi

1 Behavioral sleep problems (i.e., bedtime resistance, about RLS, which may explain why glomerulonephritis was 63
2 sleep onset delay, shorter sleep duration, night awaken- the most common cause of CKD in our studied patients. 64
3 ings) were observed among children with CKD in our study, 65
4 suggesting that behavioral and psychological factors may 4.1.1. Limitations of our study 66
5 contribute to the occurrence of sleep problems among The questionnaire results were not corroborated with 67
6 children with CKD. Depression and anxiety have been objective measurements of sleep disturbances, such as 68
7 documented as major determinants of sleep quality and polysomnography. A second problem was the small sample 69
8 disturbances in adult populations with CKD [25]. Adult size. Therefore, future studies should incorporate multi- 70
9 studies have suggested that the etiologies of sleep prob- site patients, using both subjective and objective measures 71
10 lems in patients with CKD and those on chronic intermittent such as polysomnography for assessing sleep disorders in 72
11 daytime hemodialysis are different. Functional and psy- children with CKD. 73
12 chological factors may play a more prominent role in the A strength of our study is that we studied both non- 74
13 non-dialysis-dependent CKD group, while intrinsic sleep dialysis and dialysis-dependent children with CKD; conse- 75
14 disruption (arousals, apneas, and limb movements) sec- quently, we were able to compare the prevalence of sleep 76
15 ondary to the effects of chronic intermittent dialysis may disorders across the full spectrum of chronic kidney dis- 77
16 play a more significant role in the dialysis population. This ease. In addition, the study was a case-control study 78
17 postulated different mechanism may explain the presence allowing comparisons with age and sex-matched healthy 79
18 of sleep disorders in patients with early CKD [26] in which children as controls. Furthermore, the diagnosis of sleep 80
19 psychosocial factors could be important contributors. disorders was based on structured interviews using a vali- 81
20 dated sleep questionnaire. 82
21 4.1. Associations between CKD-related factors and 83
22 sleep disorders 5. Conclusion 84
23 85
24 We found a significant positive association between the 86
Sleep disturbances are very common in children with CKD
25 serum phosphorus and CSHQ scores and a significant nega- 87
compared to healthy children. Sleep disturbances in pa-
26 tive association between the GFR and CSHQ scores, sug- 88
tients with CKD include restless legs syndrome (RLS),
27 gesting that lower GFR and hyperphosphatemia are risk 89
excessive daytime sleepiness (EDS), sleep-disordered
28 factors for sleep disturbances in children with CKD. 90
breathing (SDB), behavioral insomnias and parasomnias.
29 Consistent with our study, the positive association between 91
Therefore, it is important for practitioners caring for chil-
30 sleep disturbances and hyperphosphatemia in CKD has been 92
dren with CKD to anticipate and screen for treatable sleep
31 documented in a number of adult studies [27e29]. In 93
disorders. Early recognition and treatment of sleep distur-
32 contrast to our findings, Sinha et al [12] found no correla- 94
bances may have a positive impact on the growth and
33 tion between the stage of CKD and the prevalence of sleep 95
development of children with CKD.
34 problems; they did not observe any differences in the 96
35 incidence of sleep disorders across the stages of CKD. 97
36 Additionally, lower GFR was associated with increased Ethical approval 98
37 RLS and EDS in our study. Similarly, Roumelioti et al [13] 99
38 found that lower GFR in pediatric CKD patients was asso- “All procedures performed in the study involving human 100
39 ciated with increased daytime sleepiness. In contrast, Riar participants were in accordance with the ethical standards 101
40 et al [18] reported that RLS was more prevalent in adoles- of the institutional research committee and with the 1964 102
41 cents, but found no significant association between sleep Helsinki declaration and its later amendments or compa- 103
42 symptoms and CKD stage. rable ethical standards.” 104
43 Several uremic and non-uremic factors may explain the An informed consent was obtained from parents of all 105
44 relatively high frequency of sleep problems in children with children participating in the study. The privacy rights of 106
45 CKD. The increased prevalence of sleep disorders in CKD human subjects must always be observed. 107
46 children undergoing dialysis suggests that the dialysis pro- 108
47 cedure may be a factor in sleep disorders by causing 109
48 insufficient sleep. In addition, metabolic factors, including Funding 110
49 uremia, hyperphosphatemia, hyperparathyroidism, and 111
50 iron status, can affect sleep in CKD patients [27e30]. Low None. 112
51 production of melatonin and circadian rhythm disruption 113
52 observed in patients with chronic renal failure may also be 114
53 causative factors for sleep disturbances [31,32]. Conflict of interest 115
54 Congenital abnormalities, such as renal hypoplasia or 116
55 dysplasia, and obstructive uropathy represent the most The authors have no conflicts of interest relevant to this 117
56 common causes of CKD in children younger than 5 years of article to disclose. Q6 118
57 age. CKD children older than 5 years of age, acquired dis- 119
58 eases, such as glomerulonephritis, and inherited disorders, 120
59 such as hereditary nephropathies predominate [33]. In our
Financial disclosure 121
60 study, we excluded children less than 6 years of age, as 122
61 they could not reliably comprehend the questionnaire The authors have no financial relationships relevant to this 123
62 article to disclose. 124

Please cite this article in press as: Darwish AH, Abdel-Nabi HH, Sleep disorders in children with chronic kidney disease, International
Journal of Pediatrics and Adolescent Medicine (2016), http://dx.doi.org/10.1016/j.ijpam.2016.06.001
 IJPAM79_proof ■ 29 June 2016 ■ 7/7

+ MODEL
Sleep disorders in children 7

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Please cite this article in press as: Darwish AH, Abdel-Nabi HH, Sleep disorders in children with chronic kidney disease, International
Journal of Pediatrics and Adolescent Medicine (2016), http://dx.doi.org/10.1016/j.ijpam.2016.06.001