Introduction
Glomerular diseases refer to a group of kidney diseases characterized by inflammation and damage to the glomeruli that can affect individuals throughout their lives. In Japan, nephrotic syndrome, which is a typical glomerular disease, occurs at a higher frequency of 6.5 cases per 100,000 children per year compared with Western countries [
1]. Approximately 90% of childhood-onset nephrotic syndromes are idiopathic nephrotic syndromes (INS), with histologic types including minimal change and focal glomerulosclerosis. Although the pathogenesis of INS remains unclear, it is believed to be related to immune function disorders, circulating factors, and anomalies in glomerular slit diaphragm proteins [
2]. Minimal change nephrotic syndrome, the most common subtype, responds well to immunosuppressive therapy, with glucocorticoids used for initial remission induction [
3]. However, patients with INS often experience repeated recurrences, leading to combination therapy with immunosuppressive agents, such as calcineurin inhibitors, and renin-angiotensin system inhibitors (RASI) to minimize long-term glucocorticoid adverse effects [
3]. However, IgA nephropathy (IgAN) is primarily characterized by IgA-based immunoglobulin deposition in the glomerulus, leading to increased mesangial cell proliferation and substrate. IgAN is one of the most common types of chronic glomerulonephritis in Japan, with an estimated occurrence rate of 4.5–9.9 cases per 100,000 children per year [
4,
5]. Proteinuria in IgAN does not generally reach nephrotic levels, and recurrence is less frequent compared to INS. Although clinical characteristics differ, the treatment approaches for IgAN are similar to those for INS, including glucocorticoids, immunosuppressive agents, and RASI [
3].
Glomerular diseases including INS and IgAN progress to kidney failure when disease control is inadequate. Therefore, the impact on the lives of the children is extremely severe, often requiring long-term hospital visits and medications for treatments. Symptoms of glomerular disease, adverse effects of medications, and various lifestyle restrictions have been reported to negatively affect children’s quality of life [
6‐
10]. These impacts are also known to affect the quality of life in adolescents and adults who develop glomerular disease in childhood [
11,
12]. Although there are recommendations regarding the transition from pediatrics to adult medicine, there is insufficient evidence regarding the management of glomerular diseases during adolescence [
13,
14]. Furthermore, few studies have focused on the transition to adolescence and adulthood in patients with childhood-onset glomerular disease. In this current study, we conducted a questionnaire survey to analyze the ongoing impacts quantitatively and qualitatively from childhood to adolescence and adulthood in patients with childhood-onset glomerular disease, as well as to investigate their actual experiences in school and social life.
Discussion
In the current study, we recruited participants with two diseases, INS and IgAN, to analyze the ongoing impacts of glomerular diseases during the transition from pediatric to adult care. We focused on INS and IgAN because these were reported to be the two most common glomerular diseases in a national survey in Japan [
21]. The frequency of glomerular disease is higher in Japan compared with that in many other countries, and the diseases are diagnosed at an earlier stage because of an annual urinalysis screening program conducted in Japan from early childhood [
1,
4,
5,
22]. While the two diseases differ in their clinical characteristics, such as the severity of proteinuria and the frequency of recurrences, their treatments share many similarities, including the use of glucocorticoids, immunosuppressive agents, and RASI. Because most of the participants recruited for the current study had INS or severe IgAN, glucocorticoids were used as the primary treatment in our sample. In the current study, when we analyzed the association between age at transition and clinical information, only the number of recurrences exhibited a significant correlation, not the variable of INS or IgAN. This suggests that regardless of INS or IgAN, a lower number of recurrences is associated with a younger age at transition. However, the recurrence behaviors for INS and IgAN are considerably dissimilar, and it would be hard to draw any definite conclusions from the number of analyses performed in this study. When analyzing medication factors affecting final height and transition age, we evaluated only the use of glucocorticoids and immunosuppressive agents. We found no significant differences, except for MMF. This result may be attributed to the fact that INS patients receiving MMF were refractory to treatment. However, the number of patients in our study was not large enough, and the combination of multiple medications made it challenging to address the effects of individual medications. In order to examine the effects of each drug in detail, future studies may need to analyze not only the dose and duration of medication but also the severity of the disease and patterns of combined therapy. Furthermore, more detailed information regarding the severity of proteinuria and the number of recurrences during the disease course would allow for a more accurate analysis. A well-designed prospective study may be preferable for this purpose.
Although it has been reported that childhood-onset glomerular disease affects patient quality of life, there are few reports on the actual impact during the transition period, and there are no established guidelines for the transition to adolescence and adulthood [
6,
8‐
14,
23]. While some studies have analyzed the transition through questionnaires given to health care providers, studies that focus on the patients themselves, such as our study, are rare [
24]. In the current study, we recruited patients aged 18 years and older, who may already be in the process of transitioning, to analyze the impact of glomerular diseases on life-stage shifts. This age group may have had an advantage over younger children in directly expressing their own experiences and feelings. Our questionnaire survey provided a detailed description of the impact and distress that patients with childhood-onset glomerular disease may experience during the transition, suggesting that glucocorticoid-based medications have the most significant impact and are at the root of their suffering. Glucocorticoids can cause not only immune function suppression, hypertension, and diabetes but also adverse effects with changes in appearance, such as moon face, obesity, and hypertrichosis [
25‐
27]. In particular, increased bone resorption caused by glucocorticoids leads to secondary osteoporosis and increases the risk of fractures [
28]. Consequently, exercise restrictions may be imposed on patients who show a decrease in bone mineral density during periodic follow-up. This exercise restriction, combined with glucocorticoid-induced muscle atrophy, causes a decline in physical health for patients. Interestingly, the survey revealed that many participants reported that exercise restriction and physical decline were distressing to them. Because of accumulating evidence that regular exercise in chronic kidney disease is effective for maintaining physical function and improving lifestyle without deterioration of kidney function, exercise restrictions for patients with chronic nephritis have been relaxed in Japan since 2012 [
29,
30]. However, the impact of exercise restriction during childhood and adolescence still appears to be greater than expected. This suggests that health care providers need to take great care regarding decisions about imposing exercise restrictions on patients with glomerular diseases.
The current survey also suggests that the incidence of glomerular disease can influence the decision-making process for patients regarding higher education. Although there was a direct impact on patient learning, such as a decrease in study time and an increase in absences, some patients decided to continue their education to obtain specific qualifications, considering their physical decline. According to the responses to the questionnaire, patients believed that higher education would enable them to select a less physically demanding occupation. In addition, the positive impact of living with glomerular disease, serving as an incentive to pursue a medical career, may have also contributed to the significantly higher rate of higher education among participants in this study compared with the regional average. However, several limitations should be considered when interpreting these results. First, this study involved a small survey conducted in a single region, which might limit the generalizability of the findings. Second, the sample may have been biased; it is possible that a higher percentage of participants who selected higher education opted to participate in this study. Third, because there are many questions that require looking into the past, there may also be a recall bias. Therefore, more extensive research will be needed in the future to fully address and validate these findings. In addition, while the participants in this study were 18 years or older, future studies could include pediatric patients with glomerular disease to compare experiences during childhood with those during the transition period and beyond. In such cases, it will be necessary to carefully design a questionnaire that enables pediatric patients to adequately express their distress and feelings. Although not the focus of our study, it would also be necessary to analyze preparation for the transition, changes in feelings, and distress caused by the transition itself. We anticipate the accumulation of sustained research in the future.
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