Assessment of Health-related Quality of Life of Children with Idiopathic Nephrotic Syndrome and their caregivers in China

doi:10.21203/rs.3.rs-4922299/v1

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Research Article

Assessment of Health-related Quality of Life of Children with Idiopathic Nephrotic Syndrome and their caregivers in China

https://doi.org/10.21203/rs.3.rs-4922299/v1

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Journal Publication

published 29 Oct, 2024

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Aims: The primary aim of this study was to characterize the health-related quality of life (HRQoL) and identify the associated factors among children aged 2 to 18 years in China diagnosed with idiopathic nephrotic syndrome (INS). Additionally, the study aimed to evaluate the HRQoL and caregiving burden of their caregivers, as well as to investigate the correlation between the HRQoL of the children and that of their caregivers.

Methods: This study recruited 181 children with a diagnosis of INS from Children’s Hospital, Zhejiang University School of Medicine in China. The proxy-reported PedsQL Generic Core Module (PedsQL GCM) was used to measure the HRQoL of children, and the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) was applied to measure caregivers’ HRQoL. Differences in scale scores and total scores of PedsQL GCM were assessed using t tests and one-way ANOVA. Multivariate linear regression analysis was used to identify the associated factors of children’s HRQoL. Pearson correlation analysis was performed to assess the correlation between children’s HRQoL and caregiver’s HRQoL.

Results: HRQoL of Children with INS declines with increasing age, and children aged 5-18 years had lower scores in physical functioning, emotional functioning, school functioning, psychosocial health summary score, and total PedsQL GCM score compared to healthy children. Various factors, including the mother filling out the questionnaire, the father being unemployed, and use of other medications except for steroids were associated with worse HRQoL of children (p values < 0.05). Additionally, there is a correlation between children's HRQoL and their caregivers' HRQoL.

Conclusion: This study evaluated the HRQoL of children aged 2-18 years diagnosed with INS in China, along with the HRQoL of their caregivers. HRQoL of children was potentially influenced by multiple factors. A significant correlation was observed between the HRQoL of the children and that of their caregivers, who frequently experienced varying levels of caregiving burden. Therefore, it is recommended that healthcare professionals prioritize the optimization of HRQoL for both children with INS and their caregivers.

quality of life

idiopathic nephrotic syndrome

burden of disease

children

caregiver

Numerous glomerular disorders in pediatric populations present as nephrotic syndrome, with a majority being idiopathic in origin. Idiopathic Nephrotic Syndrome (INS), a common manifestation of chronic kidney disease, represents a major cause of morbidity and mortality globally among children and young adults (1, 2). INS is clinically defined by the triad of proteinuria, hypoalbuminemia, and edema (3, 4). The incidence of INS ranges from 1.15 to 16.9 per 100,000 children, with variations observed across different races and geographical regions (5). Clinical manifestations in children can range from mild to severe, with unpredictable patterns of relapse and remission (4, 6). The standard initial therapeutic intervention typically involves the administration of glucocorticoids. INS is frequently categorized based on the clinical response to steroid treatment into steroid-sensitive (SS) and steroid-resistant (SR) forms. In cases where the disease is SR or in instances of relapse, the use of oral immunosuppressive drugs (OID) may be required for certain pediatric patients (5, 7, 8). The extended treatment duration and propensity for relapse of INS have significant implications for the health-related quality of life of affected children and their families (8). The prolonged duration of treatment and the tendency for relapse in INS have considerable implications for the health-related quality of life of affected children and their families.

Health-related quality of life (HRQoL) encompasses multiple dimensions, including physical, psychological, and social aspects related to health. This concept serves as a critical indicator, complementing traditional health outcomes such as morbidity and mortality (9, 10). HRQoL is influenced by both individual and environmental characteristics (11). Impaired HRQoL in children with INS has been well-documented in previous studies (11–15). Factors associated with HRQoL include the duration of INS, gender, race, socioeconomic status, frequency of relapse, steroid resistance, and the use of calcineurin inhibitors (CNI) (6, 7, 9, 11, 14, 16–19). However, the majority of these studies have been conducted in developed countries, with limited data available from developing countries. A review of the literature reveals studies on the HRQoL of children with INS from Sudan, Egypt, India, Iran, and one study from China (9, 11, 17, 20–22). Furthermore, prior research has been constrained by relatively small sample sizes, especially among younger children, which has led to an incomplete understanding of the current status and determinants affecting the quality of life of Chinese children with INS. Additionally, there is a paucity of data concerning the quality of life of caregivers of patients with INS.

Therefore, we conducted this study to evaluate the HRQoL of pediatric patients diagnosed with INS and their caregivers. The primary objective was to characterize the HRQoL and identify the associated factors among children aged 2 to 18 years in China with INS. Additionally, we aimed to assess the HRQoL of caregivers and investigate the correlation between children’s HRQoL and the HRQoL of their caregivers.

Study design and participants

This was a cross-sectional, questionnaire-based survey that was led by the Department of Child Health Care and Department of Nephrology in Children's Hospital, Zhejiang University School of Medicine. Participants were recruited from both outpatient and inpatient populations at the hospital where the study was conducted, as well as from an online community facilitated through a WeChat group designed for clinician-patient communication. WeChat, a multifunctional Chinese application, supports instant messaging, social media interaction, and payment services. The WeChat group served as a significant adjunct to healthcare by disseminating disease-related knowledge and family care skills to caregivers, thereby providing them with both professional and peer support.

The inclusion criteria for the study encompassed children who (1) had been diagnosed with idiopathic nephrotic syndrome and (2) were under 18 years of age. The exclusion criteria comprised children who (1) had significant physical or psychiatric disorders and (2) whose caregivers were unable to comprehend and complete the questionnaire. Primary caregivers, who were well-acquainted with the children's health status, were invited to participate in the survey. This online survey was administered from January to August 2024. Ultimately, caregivers of 181 patients with idiopathic nephrotic syndrome completed the questionnaire.

Ethical approval

statements

This study was conducted according to the Declaration of Helsinki (23), and was approved by the Medical Ethics Committee of the Children's Hospital, Zhejiang University School of Medicine (2024-IRB-190). All caregivers gave their consents to participate in the study.

Data collection

An expert panel was convened to develop the questionnaire, comprising three senior clinicians (XW, JW, and JM) and one clinical epidemiologist (GB). The questionnaire was drafted following two rounds of discussion, informed by a review of the literature and expert opinions. Subsequently, a pre-test pilot was conducted with 20 caregivers of children with INS. Additionally, brief face-to-face interviews were conducted with 8 caregivers post-pilot to gather their feedback and suggestions.A revised version of the electronic questionnaire was ultimately employed for this study, comprising four sections: general characteristics, disease- and treatment-related characteristics, health-related quality of life of children, and health-related quality of life of caregivers. The electronic questionnaire was developed and visualized by two research assistants (LG and YS) utilizing Wenjuanxing (https://www.wjx.cn/), a widely-used online platform for creating survey questionnaires. We produced and disseminated posters featuring the QR code throughout the clinics and wards of the Department of Nephrology at the hospital where the study was conducted. Additionally, the QR code was distributed through the WeChat group. Clinicians participating in this study provided detailed explanations of its objectives to caregivers, ensuring comprehensive understanding prior to obtaining their informed consent for participation.

General characteristics encompass socio-demographic factors, such as children's age and gender, parental education, household income, marital status, and employment status, as well as medical insurance. Clinical characteristics include the onset time of idiopathic nephrotic syndrome (INS), disease duration, patient type (i.e., inpatient or outpatient), complications (e.g., hematuria, hypertension), and prescribed medications.

Children's health-related quality of life (HRQOL) was assessed using the proxy-reported PedsQL™ 4.0 Generic Core Module (PedsQL™ 4.0 GCM). Prior to data collection, authorization to use this instrument was obtained through a request on the Mapi Research Trust website (https://eprovide.mapi-trust.org/instruments/pediatric-quality-of-life-inventory), which allowed us to download the PedsQL™ without a license fee for unfunded research. The proxy-reported PedsQL™ 4.0 GCM is administered to evaluate HRQOL in children and adolescents aged 2–18 years. For children aged 2 to 4 years, the instrument comprises 21 items distributed across four scales: physiological functioning (eight items), emotional functioning (five items), social functioning (five items), and school functioning (three items). In contrast, the instrument designed for children aged 5 to 18 years includes 23 items, also organized into four scales: physiological functioning (eight items), emotional functioning (five items), social functioning (five items), and school functioning (five items). Each item is presented with five response options on a scale ranging from 0 to 4, where 0 indicates "never a problem," 1 indicates "seldom a problem", 2 indicates "sometimes a problem", 3 indicates "often a problem", and 4 indicates "always a problem". To standardize these items on a 0–100 scale, a linear transformation is applied as follows: 0 is transformed to 0, 1 to 25, 2 to 50, 3 to 75, and 4 to 100. Scale scores and total scores are computed by summing the item scores and dividing by the number of items responded to. A higher score reflects a better HRQoL. The instrument was previously validated in China, demonstrating satisfactory reliability and validity (Chen et al., 2011; Ji et al., 2011). In the current study, we computed Cronbach’s alpha coefficients, with the results detailed in Supplementary Table S1.

The health-related quality of life of caregivers was assessed utilizing the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L). The EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, each rated on a five-level scale ranging from no problems to extreme problems. Furthermore, the EQ visual analogue scale (EQ-VAS), which spans from 0 (indicating the worst imaginable health) to 100 (indicating the best imaginable health), was employed to evaluate the overall health perception of the respondent completing the questionnaire. In addition, we selected five question items from Zarit Caregiver Burden Interview (ZBI) (24) to measure specific caregiver’s burden due to taking care children with INS. The five questions are (1) “Do you feel that being with your child means you don't have enough time for yourself”, (2) “Do you feel stressed to take care of your child while also striving to balance other family or work responsibilities”, (3) “Do you feel that taking care of children has affected your own health”, (4) “Do you feel that apart from other personal expenses, you do not have enough money to take care of your child”, and (5) “Overall, how much burden do you think it is to take care of your child”.

Statistical analysis

Initially, descriptive analysis was conducted to compute means and standard deviations (SDs) for continuous variables exhibiting a normal distribution, and medians with interquartile ranges for continuous variables with a non-normal distribution. For categorical variables, frequencies and percentages were determined. Subsequently, the mean scores of the scales and the overall score of the PedsQL 4.0 Generic Core Scales (GCS) were compared with the corresponding scores of age-matched healthy children as reported in the extant literature (25, 26). Next, we employed two-independent-samples t-tests and one-way ANOVA to evaluate the differences in mean scores of the scales and the overall score of the PedsQL 4.0 GCM across various subgroups. Despite achieving statistical significance, we additionally calculated effect sizes, i.e., Cohen's d and partial eta squared (η_p²), to evaluate the clinical relevance of our findings. Cohen's d is calculated as the absolute value of the difference in mean scores between two groups divided by the largest standard deviation. The interpretation of Cohen's d is as follows: 0.2 ≤ d < 0.5 indicates a small effect size, 0.5 ≤ d < 0.8 indicates a moderate effect size, and d ≥ 0.8 indicates a large effect size (27). η_p² was calculated to estimate the effect size of a difference across three or more subgroups. Effect sizes are indicated as 0.01 ≤ η_p² < 0.06 indicates a small difference, 0.06 ≤ η_p² < 0.14 indicates a moderate difference, and η_p² ≥ 0.14 indicates a large difference. Finally, variables that demonstrated statistical significance were subsequently incorporated into the multivariate linear regression models to assess the independent associated factors of HRQoL of INS children.

Regarding caregiver’s HRQoL, we calculated proportions of reported caregiver burden across the five dimensions and the utility score of the EQ-5D-5L based on the value set of Chinese adult population (28). The means and standard deviations (SD) of the utility score and EQ-VAS scores were utilized to evaluate overall health-related quality of life. The relationships between the scale scores and total scores of the PedsQL 4.0 Generic Core Scales (GCS) with the utility score and EQ-VAS score were analyzed using Pearson correlation analysis. In addition, we calculated the proportions reported caregiver’s burden across five questions from ZBI.

All the statistical analyses were conducted by using SPSS version 27.0 (SPSS Inc., Chicago, USA). The statistical significance was indicated when p value < 0.05.

3.1. General characteristics of the study population

Table 1 presents the general characteristics of the study population. The median age of children was 4.0 years, and 68.5% were boys. Mothers filled out 76.2% of the questionnaires. 37.6% of mothers and 42.5% of fathers had a high educational level, i.e., a bachelor’s degree or above. 37.6% of families lived in urban areas. Additionally, 82.9% of the parents had someone at home to care for the sick child. 81.8% of children had health insurance.

Table 1

General and clinical characteristic of children with idiopathic nephrotic syndrome (n = 181)
Characteristic	Values*
Age of the child, year	4.0 [4.0, 5.0]
Age groups
2–4 years old	35 (19.3)
5–7 years old	59 (32.6)
8–12 years old	50 (27.6)
13–18 years old	37 (20.4)
Gender
Boys	124 (68.5)
Girls	57 (31.5)
Current weight of the child, kilogram (kg)	25.00 [18.05, 43.00]
Current Height, centimeter (cm)	122.00 [108.00, 149.50]
BMI (kg/m²)	16.41 [14.79, 20.20]
Caregiver who filled out the questionnaire
Mother	138 (76.2)
Father and others	43 (23.7)
Maternal educational level
Middle school or lower	65 (35.9)
High school	48 (26.5)
Bachelor degree or higher	68 (37.6)
Paternal educational level
Middle school or lower	56 (31.0)
High school	48 (26.5)
Bachelor degree or higher	77 (42.5)
Employment of mother
Yes	130 (71.8)
No	51 (28.2)
Employment of father
Yes	172 (95.0)
No	9 (5.0)
Annual household income (RMB)
Less than 100,000	95 (52.5)
100,000 to 200,000	35 (19.3)
More than 200,000	51 (28.2)
Parental marital status
Married	175 (96.7)
Divorced	6 (3.3)
Residence
Urban	68 (37.6)
Town or rural	113 (62.4)
Having a health insurance
No	33 (18.2)
Yes	148 (81.8)
Having someone at home to take care of the sick child
Yes	150 (82.9)
No	31 (17.1)
Having a sibling or siblings
Yes	110 (60.8)
No	71 (39.2)

* Values presented in this table presents medians, interquatile ranges, numbers, and percentages.

3.2. Clinical characteristics of the study population

Table 2 presents a summary of the clinical characteristics of the study population. The median age at disease onset was 3.7 years, which was also the median age at diagnosis of INS. At the time of this study, 29.8% of the children were making their initial hospital visit. Over the last six months, the median number of visits to a tertiary hospital was 2. The prevalence of hematuria, renal insufficiency, and hypertension among the participants was 5.0%, 9.9%, and 6.1%, respectively. Table 2 summarizes clinical characteristics of the study population. The median age of disease onset was 3.7 years, and the median age of having the diagnosis of INS was 3.7 years. 29.8% of children visited the hospital when this study was conducted for the first time. In the last six months, the median of times of visiting a tertiary hospital was 2. The percentage of presenting blood in urine, renal insufficiency and high blood pressure was 5.0%, 9.9%, and 6.1%, respectively. In the study, 27.6% of children were treated exclusively with steroids. Additionally, 48.6% utilized oral immunosuppressive drugs (OID), 28.2% received rituximab (RTX), and 28.2% were administered other medications. Notably, 71.3% of caregivers expressed that their primary concern regarding idiopathic nephrotic syndrome (INS) was its incurability.

Table 2

Clinical characteristics of children with idiopathic nephrotic syndrome (n = 181)
Characteristic	Values *
Age of onset of INS (year)	3.7 (2.3, 8.0)
Age of diagnosis of INS (year)	3.7 (2.3 ,7.7)
First-time visit of the hospital, yes	54 (29.8)
Number of visiting tertiary hospitals in the last 6 months	2 (1, 3)
Presence of hematuria, yes	9 (5.0)
Renal insufficiency, yes	18 (9.9)
Presence of hypertension, yes	11 (6.1)
Only using the steroid, yes	50 (27.6)
Medications used for treatment except for steroid
Oral immunosuppressive drug	88 (48.6)
Rituximab	51 (28.2)
Other medications	51 (28.2)
Immunosuppressive medications used for treatment
Levamisole	1 (0.6)
Mycophenolate mofetil	41 (22.7)
Cyclophosphamide	5 (2.8)
Tacrolimus	58 (32.0)
Cyclosporine A	7 (3.9)
Other	5 (2.8)
Primary concern regarding illness perceived by parents
Nephrotic syndrome cannot be cured	129 (71.3)
The physical discomforts caused by INS	11 (6.1)
Psychological problems caused by INS	8 (4.4)
Concerns about adverse effects of medications	12 (6.6)
Concerns about sequelae	9 (5.0)
The negative impact of illness on children's education	3 (1.7)
Psychological problems of caregivers	1 (0.6)
The financial burden due to the disease	7 (3.9)
Other concerns	1 (0.6)

* Values presented in this table are medians, interquatile ranges, numbers, and percentages.

3.3. Scales scores and total scores of PedsQL GCM in INS children at different age groups

Table 3 presents the means and standard deviations of scale scores and total scores of PedsQL GCM in INS children at different age groups in our study. Children aged 13–18 years had significantly lower scores in all scales as well as lower total score compared with scores at other age groups (p values < 0.05). The effect sizes ranged from 0.044 to 0.338.

In addition, we compared the mean scores of PedsQL GCM in our study population with the published scores from healthy children at the same age (25, 26). The results are presented in the Supplementary Table S2. For children aged 2 to 4 years, both the total score and the average of scale scores were significantly higher than the averages of the healthy controls (p values < 0.05) except for the mean score of school functioning (p = 0.121). For children aged 5 to 18 years, the averages of scale scores and the total score were significantly lower than the averages of the healthy controls (p values < 0.05) except for the mean score of social functioning scale (p = 0.171) .

Table 3

。 **Means and standard deviations of scales and total scores of PedsQL GCM among children with idiopathic nephrotic syndrome at different age groups (n = 181)**
	2–4 years (n = 35)	5–7 years (n = 59)	8–12 years (n = 50)	13–18 years (n = 37)	p value	Effect size (η_p²)
Physical functioning	89.20 ± 14.57	75.37 ± 17.60	53.64 ± 15.84	70.61 ± 21.64	< 0.001	0.338
Emotional functioning	82.29 ± 20.98	72.80 ± 18.06	74.50 ± 21.62	68.11 ± 27.01	0.048	0.044
Social functioning	90.86 ± 12.57	83.56 ± 19.41	84.70 ± 15.76	62.25 ± 18.08	< 0.001	0.255
School functioning	84.13 ± 24.42	69.75 ± 16.98	73.30 ± 18.51	65.27 ± 26.77	0.010	0.067
Psychosocial Health Summary Score	86.72 ± 18.03	75.17 ± 14.93	77.47 ± 15.19	65.35 ± 21.05	< 0.001	0.124
Total score	87.93 ± 16.46	75.24 ± 14.08	69.18 ± 14.41	67.18 ± 20.48	< 0.001	0.141

Values presented in this table are means and standard deviations.

*Effect size: we calculated partial eta squared (η_p²) for ANOVAs to estimate the effect size. Effect sizes are indicated as small (η_p² = 0.01), medium (η_p² = 0.06), and large (η_p² = 0.14) effects.

3.4 Differences in average scores of PedsQL GCM scales and total score

Table 4 presents differences in the mean values of PedsQL 4.0 GCM scales and total scores in the study population. We showed the variables with at least one statistically significant difference (i.e., when p value < 0.05) regarding the average scores of PedsQL 4.0 GCM scales and total scores, and the rest results are presented in Supplementary table S3. Notably, when mothers filled out the questionnaire, children had lower average scores in the scale of emotional functioning (p = 0.004), school functioning (p = 0.045), psychosocial health summary score (p = 0.010), and total score (p = 0.023) compared to those scores when fathers or others filled out the questionnaire. The average scores were significantly higher in social functioning (p < 0.001), school functioning (p = 0.017), psychosocial health summary score (p = 0.013) as well as total scores (p = 0.016) in children whose mothers had a high education compared to their counterparts. Children who visited the hospital for the first time had higher average scores in social functioning (p = 0.005), psychosocial health summary score (p = 0.016), and total scores (p = 0.023). Children on steroid-exclusive regimens had relatively higher mean score in all scales and total scores (p values < 0.05). More specifically, in terms of medical treatments, we also compared the scores of PedsQL GCM in children who exclusively used steroids with those using two or more medications. Results are shown in the Supplementary Table S3. Children had highest mean scores in all scales and total score compared to patients using oral immunosuppressive drugs (OID) and/or rituximab (RTX). Children using both OID and RTX had the lowest mean scores in all scales as well as the total score. Furthermore, we applied the Post hoc comparison and found that it indicates there was only significant differences in averages of total score of PedsQL GCM when only using steroids vs. only using OID as well as only using steroid vs. using both OID and RTX (see Supplementary table S5).

Table 4

Comparing the average scale and total scores of PedsQL GCM across groups in children with idiopathic nephrotic syndrome (n = 181)
Characteristics	Physical functioning	Emotional functioning	Social functioning	School functioning	Psychosocial Health Summary Score	Total score
Gender
Boy	73.26 ± 20.36	74.88 ± 20.95	82.06 ± 18.83	72.63 ± 21.15	76.09 ± 16.64	74.56 ± 15.97
Girl	66.31 ± 22.86	72.54 ± 24.15	78.47 ± 20.93	69.58 ± 22.09	73.18 ± 20.32	70.53 ± 19.35
p value	0.042	0.508	0.251	0.388	0.325	0.155
Effect size	0.32	0.10	0.18	0.14	0.16	0.23
Caregiver who filled out the questionnaire
Mother	69.82 ± 21.29	71.52 ± 22.46	79.90 ± 20.21	69.89 ± 20.99	73.28 ± 17.66	71.65 ± 16.88
Father and others	75.06 ± 21.36	82.56 ± 18.07	84.24 ± 16.94	77.96 ± 22.19	81.89 ± 17.48	78.99 ± 17.38
p value	0.161	0.004	0.204	0.045	0.010	0.023
Effect size	0.25	0.54	0.23	0.37	0.49	0.43
Maternal educational level
Middle school or lower	68.08 ± 22.58	71.85 ± 23.64	74.20 ± 21.37	65.52 ± 26.89	70.34 ± 21.10	69.12 ± 20.16
High school	69.08 ± 23.21	75.00 ± 22.41	79.88 ± 20.80	74.00 ± 17.31	75.24 ± 16.76	72.40 ± 16.24
College or above	75.33 ± 18.19	75.74 ± 20.04	88.10 ± 13.71	75.98 ± 16.39	79.85 ± 13.85	77.96 ± 13.38
p value	0.111	0.568	< .001	0.017	0.013	0.016
Effect size	0.03	0.01	0.10	0.05	0.05	0.05
Paternal educational level
Middle school or lower	65.80 ± 23.42	71.07 ± 24.38	73.28 ± 21.72	67.31 ± 23.76	70.24 ± 20.73	68.12 ± 19.86
High school	74.40 ± 23.59	78.33 ± 22.30	83.80 ± 16.66	73.93 ± 23.05	78.07 ± 16.91	76.23 ± 17.52
College or above	72.82 ± 17.58	73.77 ± 19.67	84.71 ± 18.09	73.36 ± 18.16	76.88 ± 15.69	75.10 ± 14.00
p value	0.078	0.240	0.002	0.215	0.056	0.033
Effect size	0.05	0.03	0.11	0.02	0.04	0.04
Employment status of father
Yes	71.69 ± 21.48	75.44 ± 20.89	82.04 ± 18.73	72.71 ± 20.76	76.31 ± 17.23	74.21 ± 16.77
No	59.12 ± 15.47	49.44 ± 28.33	59.80 ± 23.49	52.59 ± 25.62	54.55 ± 18.29	56.14 ± 16.64
p value	0.085	< 0.001	< 0.001	0.006	< 0.001	0.002
Effect size	0.67	1.05	1.05	0.86	1.22	1.08
First visit to the hospital for the diagnosis of INS
Yes	75.24 ± 21.13	77.78 ± 21.69	87.17 ± 15.96	76.81 ± 20.28	80.52 ± 16.55	78.13 ± 16.69
No	69.29 ± 21.30	72.60 ± 21.98	78.28 ± 20.34	69.66 ± 21.63	73.08 ± 18.07	71.37 ± 17.10
p value	0.086	0.147	0.005	0.054	0.016	0.023
Effect size	0.28	0.24	0.49	0.34	0.43	0.40
Presence of renal insufficiency
Yes	61.43 ± 19.73	71.39 ± 23.57	70.41 ± 22.75	68.44 ± 20.87	68.90 ± 20.34	65.38 ± 17.27
No	72.13 ± 21.32	74.45 ± 21.84	82.09 ± 18.86	71.96 ± 21.55	75.79 ± 17.60	74.07 ± 17.04
p value	0.043	0.576	0.016	0.533	0.144	0.054
Effect size	0.52	0.14	0.56	0.17	0.36	0.51
Presence of hypertension
Yes	60.34 ± 20.16	67.73 ± 24.94	67.84 ± 19.50	64.50 ± 19.92	65.80 ± 17.96	63.42 ± 17.48
No	71.76 ± 21.31	74.56 ± 21.78	81.78 ± 19.28	72.08 ± 21.52	75.73 ± 17.81	73.86 ± 17.05
p value	0.086	0.319	0.021	0.280	0.089	0.063
Effect size	0.55	0.29	0.72	0.37	0.56	0.60
Only using steroid treatment
Yes	77.04 ± 19.97	80.70 ± 21.92	87.43 ± 15.22	80.61 ± 21.38	82.81 ± 17.08	80.41 ± 16.76
No	68.79 ± 21.51	71.64 ± 21.54	78.45 ± 20.45	68.41 ± 20.62	72.39 ± 17.48	70.66 ± 16.69
p value	0.020	0.013	0.005	0.001	< 0.001	0.001
Effect size	0.40	0.42	0.50	0.58	0.60	0.58

Values presented in this table are means and standard deviations.

*Effect size were calculated as Cohen’s d and partial eta squared (η_p²) to estimate clinical relevance. Effect sizes are indicated as small (d = 0.2, η_p² = 0.01), medium (d = 0.5, η_p² = 0.06), and large (d = 0.8, η_p² = 0.14) difference.

3.5 Associated factors of the total PedsQL GCM score

Table 5 shows results of multivariate linear regression analyses to assess associated factors of the HRQoL in children with INS measured by PedsQL GCM. Factors significantly associated with children’s HRQoL include mothers filling out the questionnaire (β = 6.20; 95% CI: 0.12, 12.27; p = 0.046), non-emoloyment status of fathers (β=-12.12; 95% CI: -23.42, -0.82; p = 0.036) and not exclusively using steroid treatment (β= -6.60; 95% CI: -12.62, -0.58; p = 0.032). The adjusted R² is 0.132.

Table 5

Associated factors of total PedsQL GCM score in the multivariate linear regression analyses
	PedsQL GCM Total score
	β (95% confident interval)	P value
Caregiver who filled the questionnaire
Mother (n = 138)	Reference
Father and others (n = 43)	6.20 (0.12, 12.27)	0.046
Maternal educational level
University or higher (n = 68)	Reference
High school (n = 48)	-5.75 (-13.82, 2.32)	0.161
Middle school or lower (n = 65)	-6.13 (-16.21, 3.95)	0.232
Paternal educational level
University or higher (n = 77)	Reference
High school (n = 48)	3.41 (-4.86, 11.68)	0.417
Middle school or lower (n = 56)	-1.29 (-11.11, 8.53)	0.796
Employment of father
Yes (n = 172)	Reference
No (n = 9)	-12.12 (-23.42, -0.82)	0.036
First onset of symptoms
Yes (n = 54)	Reference
No (n = 127)	-3.27 (-9.32, 2.77)	0.286
Steroid
Yes (n = 50)	Reference
No (n = 131)	-6.60 (-12.62, -0.58)	0.032
Adjusted R²	0.132

3.6 Caregiver’s Health-related Quality of Life and Caregiver’s burden

Caregiver’s HRQoL profile composed of the five health dimensions is shown in Fig. 1. The percentage of reporting “no problem” in mobility, looking after themselves, doing usual activities, pains and discomforts and feeling worried, sad or unhappy was 52.41%, 76.47%, 93.58%, 95.19% and 94.12%, respectively. Notably, 38.50% of caregivers reported slight problems in the dimension ‘feeling worried, sad or unhappy’, 8.02% moderate problems, 0.53% severe problems and 0.53% extreme problems. As shown in the Supplementary Table S6, the mean of EQ-5D-5L utility score is 0.94 with a standard deviation as 0.08, and the median of EQ-5D-5L VAS score is 89 (interquartile range: 79, 100). Futhermore, Table 6 shows the scale scores and total score of PedsQL GCM are statistically significantly correlated to EQ-5D-5L utility score and VAS score (p values <0.05). In addition, Fig. 2 demonstrates the specific caregiver’s burden due to taking care of children with INS.

Table 6

The correlation between PedsQL GCM scale/total scores and EQ-5D-5L utility and VAS score
	Utility score		VAS
	Pearson r	P value	Pearson r	P value
Physical functioning	0.299	< 0.001	0.285	< 0.001
Social functioning	0.223	0.003	0.246	< 0.001
Emotional functioning	0.338	< 0.001	0.270	< 0.001
School functioning	0.338	< 0.001	0.241	0.002
Psychosocial Health Summary Score	0.352	< 0.001	0.302	< 0.001
Total score	0.374	< 0.001	0.337	< 0.001

In the present study, we have conducted an assessment of the health-related quality of life (HRQoL) among children aged 2 to 18 years with Idiopathic Nephrotic Syndrome (INS) in China, as well as the HRQoL of their caregivers and the burden experienced by caregivers in managing children with INS. Our findings indicate that children's HRQoL declines with increasing age. Various factors, including parental educational level, father's employment status, and medication treatment plans, may be associated with children's HRQoL. Additionally, there is a correlation between children's HRQoL and their caregivers' HRQoL. Nearly 70% of caregivers reported experiencing a significant burden due to the responsibilities of caring for children with INS.

We found that the health-related quality of life (HRQOL) of children aged 2 to 4 years was superior to that reported for healthy children in the existing literature (25). This discrepancy may be attributed to the relatively small sample sizes in both our study (n = 35) and the referenced study (n = 36) (25). Additionally, the referenced study was conducted in 2005, which may not accurately reflect the current HRQOL profile of Chinese children aged 2–4 years (25).

Our study found HRQOL of children aged 2 to 4 years in our study was better than that reported for healthy children in the existing literature (25). This discrepancy may be attributed to the relatively small sample size of children in both our study (n = 35) and the referenced study (n = 36) (25). Additionally, the referenced study was conducted in 2005, which may not accurately reflect the current HRQOL profile of Chinese children aged 2–4 years (25). Furthermore, the clinical stage and duration of INS may also impact children’s HRQOL. Roussel et al. demonstrated that HRQOL scores for children with steroid-dependent nephrotic syndrome and steroid-resistant nephrotic syndrome were elevated and nearly comparable to those of children without chronic illness (8). This finding is attributed to the fact that the study populations were in a stable remission period, which is associated with higher HRQOL scores. Similarly, children aged 2 to 4 years experienced a relatively short duration of the disease and a lower frequency of relapse, potentially resulting in a quality of life comparable to that of the general population.

Our study found HRQOL of children aged 5 to 18 years in our study to be worse than that reported for healthy children in the existing literature (25), which is consistent with previous studies (4, 9, 11, 17, 29). Selewski et al. observed that INS children exhibited lower scores on measures of social and school functioning. Similarly, a study conducted in India involving 102 patients revealed that their scores in physical, social, and school functioning were significantly lower compared to those of healthy children, with school functioning being the most adversely affected (4, 17). Additionally, a recent study from the Netherlands indicated that children aged 8 to 18 years experienced a notable decline in scores related to physical and emotional functioning, as well as in the overall HRQoL (29). These discrepancies may be attributable to variations in cultural contexts, healthcare systems across different nations, and the stage and relapse frequency of the disease in patients (7, 11, 20).

In our study, the scores for emotional functioning, school functioning, psychosocial health summary, and the overall total were higher when fathers completed the questionnaire compared to when mothers did. This discrepancy may be attributed to fathers' lower emotional sensitivity, which could result in a relatively more optimistic outlook and reduced anxiety. It is noteworthy that the score for physical functioning did not reach statistical significance. This phenomenon could be attributed to the objective nature of the physical functioning questions in the PedsQL GCM. Our findings aligned with previous research, which also indicated that caregivers who completed the questionnaire reported similar outcomes (30). Our findings indicate that children’s HRQoL is significantly better, both at the scale level and overall, when their parents possess higher educational attainment and are employed. This observation aligns with the earlier study by (31), which demonstrated a positive correlation between paternal education and proxy-reported HRQoL. It is plausible that families with relatively higher socioeconomic status are better equipped to offer the necessary support for managing the care of ill children, thereby contributing to an enhanced HRQoL. Remarkably, we identified that when fathers were unemployed, children's HRQoL was significantly impaired across all scales and at the overall level, with the effect size indicating moderate to large differences. Even after adjusting for other covariates, this variable remained statistically significant in the regression model. Considering the social and cultural context of China, paternal unemployment can have a substantial impact on the family, particularly in medical decision-making.

In this study, children with newly diagnosed INS exhibited higher scores in social functioning, psychosocial health summary, and overall PedsQL GCM scores. This observation is attributed to their early stage of the disease, during which they experienced relatively minimal adverse effects from treatment and pain. Conversely, patients experiencing disease recurrence and prolonged duration demonstrated a significantly diminished quality of life compared to those with initial onset, with the effect size approaching a moderate level. Our findings are consistent with previous studies that have documented the adverse effects of relapse on HRQoL (4, 9, 11, 17, 29). Furthermore, our study indicates that social and psychosocial functioning are particularly impacted by relapse. This phenomenon may be attributed to the necessity for frequent hospital visits, reduced social interaction, the cumulative psychological impact of complications such as edema, obesity, and hirsutism, and the resultant isolation from peers (11, 17, 20).

Regarding pharmacological interventions, our study found that patients on a steroid-exclusive regimen were reported a higher quality of life compared to those who used oral immunosuppressive drugs (OID) and/or rituximab (RTX). This association remained statistically significant even after adjusting for covariates. This observation is plausible, as children treated with only steroids most likely were in the initial stages of the disease and experienced less disease-related pain and fewer complications. Children undergoing treatment with OID or RTX required frequent hospitalizations and experienced the discomfort associated with RTX infusions, which adversely impacted their emotional well-being and reduced their time for social interactions and school activities.

Strengths and limitations

This study exhibits several strengths. Firstly, it investigates the HRQoL of children with INS in China, encompassing a relatively large sample size of patients aged 2 to 18 years. Notably, the study employs specialized PedsQL GCM scales for children aged 2 to 4 years, thereby enhancing the evaluation of quality of life in this younger age cohort. Secondly, we conducted a thorough assessment of a wide range of potential influencing factors to enhance the understanding of health status and medical care among children with INS. Additionally, we employed effect size metrics, specifically Cohen’s d and η_p², to evaluate the clinical relevance of differences in HRQoL scores across subgroups. This approach addresses the limitations of relying solely on statistical significance.

However, the study presents several limitations that warrant attention. Firstly, it is a single-center study lacking large-sample standard data of Chinese children as a healthy control group. Secondly, the cross-sectional design precludes follow-up quality of life (QOL) measurements over time, thereby limiting the ability to establish causality. Additionally, even though the previous study showed strong agreement that the proxy-reported questionnaire is reliable (17), incorporating both proxy- and self-reported outcomes may provide more comprehensive insights.

This study evaluated the HRQoL of children aged 2–18 years diagnosed with INS in China, along with the HRQoL and caregiving burden of their caregivers. The findings indicate a decline in children's HRQoL with increasing age, potentially influenced by factors such as parental education, paternal employment status, and medication regimens. A significant correlation was observed between the HRQoL of the children and that of their caregivers, who frequently experience varying levels of caregiving burden. Therefore, it is recommended that healthcare professionals prioritize the optimization of HRQoL for both children with INS and their caregivers.

HRQoL - Health-related Quality of Life

INS - Idiopathic Nephrotic Syndrome

PedsQL GCM - Pediatric Quality of Life Inventory Generic Core Module

EQ-5D-5L - EuroQol five-dimensional questionnaire, five-level version

OID - Oral Immunosuppressive Drugs

RTX - Rituximab

SS - Steroid-Sensitive

SR - Steroid-Resistant

CNI - Calcineurin Inhibitors

BMI - Body Mass Index

ZBI - Zarit Burden Interview

VAS - Visual Analogue Scale

SPSS - Statistical Package for the Social Sciences

SD - Standard Deviation

ANOVA - Analysis of Variance

CI - Confidence Interval

RMB - Renminbi (Chinese currency)

Ethics approval and consent to participate: The study protocol was conducted according to the Declaration of Helsinki, and was approved by the Medical Ethics Committee of the Children's Hospital, Zhejiang University School of Medicine (2023-IRB-190). All caregivers gave their consents and voluntarily participated in the study.

Consent for publication: not applicable.

Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests: The authors declare that they have no competing interests.

Funding: There is no funding related to the present study.

Authors' contributions: Xia Wang, Jianhua Mao and Guannan Bai were involved in the study conceptualization and design. Xia Wang, Jingjing Wang, Chunyue Feng, Haidong Fu, Huijun Shen, and Xiujuan Zhu collected data. Lejing Guan and Yifei Shao carried out statistical analyses and prepared all the tables /figures. and G.B. wrote the main manuscript texts. Abdul Rafay prepared the supplementary tables. Xia Wang, Danny Junyi Tan and Guannan Bai wrote the first draft of this manuscript. Jianhua Mao and Guannan Bai supervised the whole project. All authors reviewed the manuscript and provided critical revisions of the article for important intellectual content. All the authors contributed to the interpretation of the data and approved the article's final version.

Acknowledgements:

We gratefully thank all the INS patients and their families who were willing to participate in this study. We thank the Pediatric Evidence-based Medical and Clinical Research Laboratory, an internal institute of the National Clinical Research Center for Child Health, for the great support in terms of methodology and data analysis.

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No competing interests reported.

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Assessment of Health-related Quality of Life of Children with Idiopathic Nephrotic Syndrome and their caregivers in China

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Abstract

Figures

Background

Methods

Study design and participants

Data collection

Statistical analysis

Results

3.1. General characteristics of the study population

3.2. Clinical characteristics of the study population

3.4 Differences in average scores of PedsQL GCM scales and total score

3.5 Associated factors of the total PedsQL GCM score

3.6 Caregiver’s Health-related Quality of Life and Caregiver’s burden

Discussion

Strengths and limitations

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

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