786 evaluate how disease and treatment is impacting an individual child and sometimes his or her family This allows providers to consider poten tial interventions to address areas of HRQOL that are su[.]
786 e valuate how disease and treatment is impacting an individual child and sometimes his or her family This allows providers to consider potential interventions to address areas of HRQOL that are suboptimal or poor In addition to this individual level of assessment, more attention is being paid to HRQOL as an important measure of the success of a given treatment within a population Indeed, WHO defines health as “a state of complete physical, mental, and social wellbeing, not merely the absence of disease.” The value of treatment, even if successful clinically, is diminished if the patient does not perceive adequate HRQOL. Thus, information about HRQOL can be used to evaluate the impact of treatments or programs on groups of patients, to inform standards of care and policy for identified patient populations One example of an effort within nephrology to standardize outcomes that include aspects of HRQOL is SONG-Kids (Standardised Outcomes in Nephrology – Children and Adolescents) The aim of this initiative is to enhance the relevance, transparency, and impact of research designed to improve the lives of children across all stages of CKD and their families and, importantly, includes patients and their caregivers in the process of identifying key outcomes [40] Assessment of HRQOL Measures of HRQOL can be categorized into three types: generic HRQOL measures, disease- specific measures, and measures of functional disability The reported psychometric properties of available pediatric instruments tend to be fair to good, but the full psychometric picture is often incomplete [28] An important weakness of current measures is the absence of empirically derived minimal clinically important difference scores; this would allow providers to better interpret the magnitude of change that is observed and identify thresholds for meaningful change [28] Three measures of generic HRQOL and one disease- specific measure that have been used with children who have ESRD are presented below, with a brief description of each R J Johnson and S L Furth Child Health and Illness Profile (CHIP) The Child Health and Illness Profile (CHIP) has child and adolescent self-report versions and a parent-proxy report The adolescent version (CHIP-AE) is for ages 11–17 and has been used with youth who have CKD. It has 153 items, assesses six domains of health (discomfort, satisfaction, disorders, achievements, resilience, and risks), and requires approximately 20 minutes to complete It has demonstrated test-retest and internal reliability and criterion and construct validity [30] Child Health Questionnaire The Child Health Questionnaire (CHQ; [24]) is a generic HRQOL measure that includes both parent-proxy report for children ages 5–18 and child self-report for ages 10–18 years This measure requires approximately 20 minutes to complete and assesses 12 domains of health (physical functioning, limitations in schoolwork and activities with friends, general health, bodily pain and discomfort, limitations in family activities, emotional/time impact on the parent, impact of emotional or behavior problems on schoolwork and other daily activities, self-esteem, mental health, behavior, family cohesion, and change in health) This measure has demonstrated internal consistency and concurrent validity [24] PedsQL Generic Core Scales The Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales is a 23-item generic (not disease-specific) measure of healthrelated quality of life [45] It assesses four domains of health (physical functioning, emotional functioning, social functioning, and school functioning), and scores from these four domains are used to calculate three summary scores: psychosocial health, physical health, and a total scale score The PedsQL was developed for youth and young adults 2–25 years; self-report forms for ages 5–18 years are avail- 40 Health-Related Quality of Life of Children and Adolescents on Dialysis able, as well as parent-proxy forms for children ages 2–18 The PedsQL takes approximately 4 minutes to complete and has been translated into several languages It has demonstrated feasibility, reliability, and validity for use with children broadly, including those who have ESRD [17] The parent-proxy report has also been shown to be feasible, reliable, and valid with youth 2–16 years of age [44] PedsQL ESRD Module In addition to the generic form of the PedsQL, a 34-item PedsQL End-Stage Renal Disease Module was developed for use with children who have ESRD [17] This measure has seven scales relevant to ESRD: general fatigue, side effects of kidney disease, treatment problems, family and peer interactions, worry, perceived physical appearance, and communication Child selfreport and parent-proxy reports are available for patients ages 5–18 years, and a parent-proxy report is available for children 2–4 years The format is similar to the PedsQL Generic Core Scales Goldstein et al reported initial support for the use of the ESRD module with children who have ESRD. Several scales demonstrated acceptable internal consistency reliability, and the measure demonstrated good construct validity Ideally, the ESRD module would be used in conjunction with the Generic Core Scales, with both patient and parent informants, in order to capture comprehensively the child’s HRQOL from both patient and parent perspectives arly Investigations of the Quality E of Life of Youth on Dialysis The first study to evaluate HRQOL in pediatric dialysis patients using a multidimensional, standardized measure of HRQOL was published in 1994 by Kurtin et al [23] In this pilot study, a measure of HRQOL was administered to 20 adolescents on hemodialysis Overall, youth on hemodialysis reported impaired HRQOL. Those who were rated as less adherent by their health- 787 care providers reported more pain, poorer general and mental health, and lower family cohesion This pilot study led to the first multicenter, longitudinal study of QOL of children with chronic kidney disease (CKD) in the United States, initiated by Furth et al The study expanded on Kurtin et al.’s pilot research to validate two multidimensional generic quality of life measures (the CHQ-Parent Form and the CHIP-AE) for use with children who have CKD. The parents of 78 patients with CKD completed the CHQ longitudinally (over years); results indicated that parents reported poorer physical health for their children as their estimated glomerular filtration rate (eGFR) declined and that height gain was associated with better parent ratings of the physical and psychosocial functioning of their children [9] This same study also examined adolescent self-report of HRQOL using the CHIP-AE. The sample included adolescents across multiple stages of CKD, including those on dialysis and post-transplant, with age-, socioeconomic-, and gender-matched controls They found that the CHIP-AE distinguished between adolescents with kidney disease and the healthy control group in several domains [14] Children with CKD reported lower satisfaction with health and more restriction in activity, with those on dialysis reporting the lowest levels of functional health urrent Findings: Quality of Life C of Youth on Dialysis A number of cross-sectional studies have reported poorer HRQOL for children with CKD and in particular for youth on dialysis Goldstein et al [16] evaluated the HRQOL of 85 children on dialysis or with a renal transplant using both parent- proxy and self-report data from the PedsQL Generic Core Scales Ratings derived from this patient group were compared to the ratings of a matched control group of healthy children Results indicated that children with ESRD had worse HRQOL across domains – physical, emotional, social, and school – than the healthy control group, with dialysis patients reporting worse HRQOL than transplant patients McKenna 788 et al [25] reported both parent-proxy and self- reported HRQOL for patients with a range of CKD, including dialysis and transplant, and compared self- and parent-reported HRQOL to published norms Patients on dialysis reported lower physical and school functioning ratings compared to a healthy control group but had similar ratings of emotional and social functioning In contrast, parent-proxy ratings of youth on dialysis were lower than the healthy control group across all domains of the PedsQL. Dotis et al [6] assessed the HRQOL of 55 children ages 8–18 years, a subset of whom were on dialysis (n = 14), and found that patients reported lower physical HRQOL than a healthy control group In a study that assessed the HRQOL of 55 children with ESRD (dialysis or transplant), patients with ESRD had significantly lower scores than a healthy control group across all domains of HRQOL, for both self- and parent-proxy report, with patients on dialysis reporting poorer physical and school functioning than those with renal transplants [8] Similar findings were reported by Kilicoglu et al [22] for another group of dialysis and transplant patients; those receiving renal replacement therapy reported poorer HRQOL than a control group In addition to El Shafei et al., several other studies have indicated that patients on dialysis report poorer HRQOL than patients who have undergone renal transplant In a study using the PedsQL ESRD module only, transplant patients (n = 37), versus those on dialysis (n = 55), reported better quality of life in one domain of self-report, and their parents reported better HRQOL in two domains [29] In another study examining HRQOL in dialysis versus transplant, dialysis patients scored lower than healthy controls and transplant patients on a measure of health satisfaction [31] Varni et al [44] compared the parent-proxy and self-reports of HRQOL of children in ten disease groups, including ESRD, and found that compared to youth who had undergone renal transplant, children on hemodialysis reported significantly impaired physical and overall HRQOL and their parents reported poorer HRQOL across all domains for their children on hemodialysis R J Johnson and S L Furth compared to those who had received a transplant For the subset of children on peritoneal dialysis, their parents reported lower emotional functioning for their children compared to children who had received a transplant In contrast, in a study of 192 youth, Splinter et al [35] found that both dialysis and renal transplant patients self-reported impaired HRQOL compared to healthy controls and youth with other chronic health conditions Those undergoing preemptive transplants reported higher physical HRQOL but otherwise had scores similar to those who underwent non-preemptive transplant Rather than type of renal replacement therapy, it was presence of comorbidities that was the most important determinant of impaired HRQOL. In one of few studies to examine this question longitudinally, Wightman et al [47] retrospectively examined the longitudinal HRQOL data for 56 children who were on dialysis before undergoing kidney transplant They found that reported HRQOL improved over time for all scales on the PedsQL ESRD module; for patients with both pre- and post-transplant assessments, total scores increased on both self-report and parent-proxy reports In another longitudinal study of HRQOL that included only patients on dialysis, Neul et al [27] found that patients on dialysis longer, particularly females, had worse ratings of emotional functioning Parents of older youth and youth on dialysis longer reported worse functioning for their children on multiple domains of HRQOL and perceived their children’s school functioning as deteriorating over time With regard to long-term outcomes, Tjaden et al [38] examined social outcomes 30 years later for all Dutch patients born before 1979 who started RRT at less than 15 years of age These patients completed a measure of HRQOL and reported on other sociodemographic outcomes Eighty-nine of 152 patients still alive responded; those on dialysis reported impaired physical HRQOL, but mental health scores were comparable to the general population Those with a history of ESRD had fewer offspring, were less likely to have income equal to or above average, and were less likely to be employed than the general population Lower 40 Health-Related Quality of Life of Children and Adolescents on Dialysis HRQOL was associated with disabilities, comorbidities, and unemployment A number of studies have used qualitative methods to evaluate the HRQOL of children with advanced CKD. Tong et al [39] asked 27 adolescents and young adults awaiting transplant or on dialysis to keep a daily journal and complete interviews regarding their experiences and perspectives This qualitative data indicated that these patients had impaired self-worth, perceived a precarious future, and felt limited with regard to their physical and psychosocial capacities; they did not perceive having the same opportunities and potential for success as their healthy peers In the same sample, using cross-sectional methodology, Tong et al [41] examined perceived HRQOL using a visual analogue scale and three utility-based measures of HRQOL. They found that these adolescents and young adults reported low HRQOL, and utility-based HRQOL scores suggested they were willing to trade considerable life expectancy for perfect health Dialysis patients reported the highest burden of kidney disease (interference with daily life, time burden, and the feeling of being a burden to others) Tjaden et al [37] conducted a systematic review of 17 qualitative studies to describe the experiences and perspectives of adolescents on dialysis The selected group of studies included 143 children and adolescents on dialysis and identified five main themes underlying these children’s experience of dialysis These included loss of control, restricted lifestyle, use of coping strategies, managing treatment, and feeling different They concluded that children undergoing dialysis often have poor self-esteem and a pervasive sense of losing identity, body integrity, control, and independence, and these children perceive that their disease limits their opportunities in life Comorbidities and HRQOL As reported above, the presence of increased comorbidities tends to negatively impact the HRQOL of children with ESRD. With regard to specific comorbidities, Stabouli et al [34] examined sleep disorders in children with CKD, iden- 789 tifying seven relevant studies, five of which included children on dialysis They found that the prevalence of sleep disorders ranged from 77% to 85% among patients on dialysis Two of these studies also assessed HRQOL within the context of sleep disturbance Davis et al [5] found high rates of sleep disturbance among children with CKD and found that the presence of sleep disturbance correlated with a decline in HRQOL independent of disease group (pre-dialysis, dialysis, or transplant) or estimated GFR. Riar et al [32] assessed children with CKD for restless legs syndrome (RLS) specifically, in a prospective, cross- sectional study that compared patients to a healthy control group and included assessment of HRQOL using the PedsQL Generic Core Scales They found that RLS was more common in children with CKD, and there were no associations between CKD stage (pre-dialysis, dialysis, or transplant), etiology, or duration of disease and presence of RLS. Children with RLS were more likely to rate the quality of their sleep as “bad” or “very bad,” and on parent-proxy report children with RLS had poorer psychosocial and total HRQOL scores Short stature, another comorbidity of CKD, has been associated with lower HRQOL. One study found that children with CKD who had short stature reported lower self-esteem and lower satisfaction with their overall health than those with more normal growth [31] In studies of children with mild to moderate CKD, in one study short stature was associated with lower physical HRQOL [15], and in another it was associated with lower ratings of HRQOL by both parents and patients [19] Tjaden et al [36] reported in a 30-year follow-up study of childhood ESRD that short stature in adulthood was associated with less likelihood of having children Another study found that both growth hormone use and height gains were associated with improved parentproxy scores in the HRQOL domains of physical and social functioning [1] Unfortunately, many children with CKD and short stature not receive growth hormone therapy [43]; this is a potentially modifiable comorbidity, and improvement in height may lead to greater satisfaction with health and better quality of life R J Johnson and S L Furth 790 Anemia is a common comorbidity of CKD and has been associated with reduced HRQOL. For children with mild to moderate CKD, anemia has been associated with lower parent-proxy scores on the social functioning scale of the PedsQL [15] In a study of 105 adolescents with CKD stages 1–5, the parents of patients with hematocrit less than 36% (n = 75) reported that their children were less likely to participate in activities at school and with their friends and rated them as being less physically active than children with hematocrit greater than 36% [13] In another study of children on dialysis, those who were anemic reported a negative impact on HRQOL in the areas of sleep, alertness, emotions, and daily activities [42] In contrast, in a study that used level of hemoglobin to define anemia (