In the present study, we have conducted an assessment of the HRQoL among children aged 2 to 18 years diagnosed with 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 burden to some extent due to the responsibilities of caring for children with INS.

Our findings indicated that the HRQoL score of children aged 2 to 4 years in our study was superior to that reported for healthy children in the existing literature [25]. This finding potentially attributed to factors such as the young age of the children, the brief duration of INS, not attending schools, and the absence of perceived symptoms. Consequently, these children may not present many changes in functioning, and their caregivers may not regard this health condition as impactful to children’s lives, as it does not interfere with their schooling or other activities. In addition, this observed discrepancy may be due to the relatively small sample sizes in both our study (n = 35) and the referenced study (n = 36) [25]. The referenced study was conducted in 2005, which may not accurately represent the current HRQoL profile of Chinese children aged 2 to 4 years [25]. Moreover, the clinical stage and duration of INS can affect children's HRQoL. Roussel et al. found that children with steroid-dependent or steroid-resistant nephrotic syndrome had HRQoL scores similar to those of healthy children [8], likely because the study participants were in stable remission. Similarly, children aged 2 to 4 years exhibited a relatively brief disease duration and a lower incidence of relapse, which may contribute to a quality of life comparable to that of the general population.

Our study revealed that INS children’s HRQoL aged 5 to 18 years was inferior to that reported for healthy children in the existing literature [25], a finding that aligned with previous research [4, 9, 11, 17, 29]. Selewski et al. found that children with INS demonstrated lower scores on assessments of social and school functioning. In a similar vein, a study conducted in India involving 102 participants indicated that these children scored significantly lower in physical, social, and school functioning compared to their healthy counterparts, with school functioning being the most severely impacted [4, 17]. Furthermore, a recent study conducted in the Netherlands revealed that children aged 8 to 18 years exhibited a significant decline in scores related to physical and emotional functioning, as well as overall HRQoL [29]. These disparities may be attributed to differences in cultural contexts, healthcare systems across various countries, and the stage and relapse frequency of the disease among patients [7, 11, 20].

In our study, the scores for emotional functioning, school functioning, psychosocial health summary, and the total score were higher when fathers or others completed the questionnaire compared to mothers. This discrepancy may be attributed to fathers' lower emotional sensitivity, potentially resulting in a relatively more optimistic outlook and reduced anxiety. Notably, the score for physical functioning did not reach statistical significance, which may be due to the objective nature of the physical functioning questions measured by the PedsQL™ 4.0 GCM-Physical Functioning Scale. Our findings align with previous research, which also indicated that caregivers who completed the questionnaire reported similar physical health related outcomes [30]. Our findings suggest that children’s HRQoL is significantly better, both at the scale level and overall level, when their parents possess higher educational attainment and are employed. This observation aligns with the earlier study [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 positioned to provide the necessary support for managing the care of ill children, thereby contributing to an enhanced HRQoL. Our findings indicate that paternal unemployment is associated with a significant impairment in children's HRQoL across all scales and at the overall level, with effect sizes suggesting moderate to large differences. This variable remained statistically significant in the regression model even after adjusting for other covariates. In the context of Chinese social and cultural norms, paternal unemployment may exert a substantial influence on family dynamics, particularly in the realm of medical decision-making.

In this study, children with newly diagnosed INS exhibited elevated scores in social functioning, psychosocial health summary, and overall PedsQL™ 4.0 GCM scores. This observation can be attributed to the early stage of the disease, during which they experienced relatively minimal adverse effects from treatment and pain. In contrast, patients with recurrent disease and prolonged duration demonstrated a significantly diminished quality of life compared to those with initial onset, with the effect size nearing 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]. Additionally, our study reveals that social and psychosocial functioning are notably affected by relapse. This phenomenon may be attributed to the necessity for frequent hospital visits, diminished social interactions, 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 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 finding is plausible, as children treated with only steroids were likely in the initial stages of the disease, experiencing less disease-related pain and fewer complications. Children receiving treatment with OID or RTX required frequent hospital admissions and endured discomforts associated with RTX infusions. These factors negatively affected their emotional well-being and diminished their opportunities for social interactions and participation in school activities.

Caregivers are essential to the long-term management of children with INS, a chronic condition necessitating prolonged treatment. Over time, caregivers are responsible for ongoing proteinuria monitoring, medication administration, management of specialized diets, coordination of frequent hospital follow-up visits, addressing the emotional well-being of the children, and making critical decisions. Consequently, the role of a caregiver for a child with INS is both stressful and demanding. Our study revealed that approximately 30% of caregivers assessed their caregiving burden as moderate or higher. The demands of caring for a sick child often result in insufficient personal time, challenges in balancing work and life responsibilities, perceived financial strain, and deteriorating health. These negative effect may accumulate over time and adversely affect their HRQoL [32]. Liu et al. reported that anxiety was present in 63.4% of caregivers of children with INS, and depression was observed in 68.4% of parental caregivers [33]. Understanding the correlation between the HRQoL of both children and their caregivers may aid in the development of targeted and personalized health education strategies. Such strategies can assist caregivers in adapting to their roles and achieving optimal health outcomes for the children.

This study demonstrates several notable strengths. Firstly, it examines the HRQoL of children with INS in China, utilizing a relatively large sample size of patients aged 2 to 18 years. Importantly, the study incorporates specialized instrument PedsQL™ 4.0 GCM for children aged 2 to 4 years, thereby improving the assessment of quality of life within this younger demographic. Secondly, a comprehensive evaluation of a broad spectrum of potential influencing factors was conducted to enhance the understanding of health status and medical care among children with INS. Furthermore, effect size metrics, specifically Cohen’s d and \(_^\), were utilized to offer a more nuanced analysis of the findings and to assess the clinical relevance of differences in HRQoL scores across subgroups. This methodological approach addresses the limitations inherent in relying solely on statistical significance.

However, the study presents several limitations that warrant attention. Firstly, it is a single-center study that lacks a large-sample standard dataset of Chinese children to serve as a healthy control group. Secondly, the cross-sectional design precludes longitudinal HRQoL assessments over time, thereby limiting the ability to establish causality. Additionally, it is imperative to monitor these children longitudinally to assess the development of their quality of life (QOL) over time. This approach will enable health professionals, patients, and caregivers to comprehend the impact of INS and to implement timely, targeted interventions aimed at enhancing patient well-being. Consequently, we recommend that future research adopt a longitudinal study design or incorporate follow-up assessments of HRQoL. Thirdly, 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. Fourthly, the present study exclusively utilized a quantitative approach, which yielded a comprehensive dataset elucidating the HRQoL profile of children with INS in China. Although a range of associated factors influencing children's HRQoL has been identified, this approach only partially explains the HRQoL outcomes observed in children with INS. To obtain a more profound understanding of this issue, we recommend incorporating qualitative investigations alongside quantitative methods in future research, thereby adopting a mixed-methods study design.