Searching the electronic medical records for patients over 18 years old with INS or IgAN in childhood, the three facilities identified a combined total of 50 INS patients (30 males and 20 females) and 46 IgAN patients (24 males and 22 females). Among these patients, questionnaires were sent to 42 INS patients (25 males and 17 females) and 41 IgAN patients (21 males and 20 females) whose willingness to participate in the study was confirmed. Questionnaires were then collected from 22 INS patients (14 males and 8 females) and 23 IgAN patients (7 males and 16 females) patients (collection rate, 54.2%). After the exclusion of some patients because of missing clinical information, the final analysis included 15 INS patients and 23 IgAN patients (Fig. 1). Collection rates differed between genders, with more returns from female patients (male 45.7% vs. female 64.9%). There were no significant differences in collection rates based on the age of patients or the methods of distribution (mailing 58.3% vs. hand-delivering 58.8%).

Recruitment diagram. A total of 96 participants were recruited for the current study using electronic medical records from three facilities. Finally, 15 INS patients and 23 IgAN patients were included in the analysis

The mean age of onset for INS and IgAN patients in this study was 9.6 and 11.4 years, respectively. This relatively high average age of onset for INS may have been caused by the limit of approximately 10 years on retrospective searches using electronic medical records. Otherwise, there were no other findings of note at the time of onset of disease in the participants in this study (Table 1). The responses to initial glucocorticoid treatment (2 mg/kg or 60 mg/m2 for 4 weeks) in INS patients were as follows: steroid-dependent, 8 (53.3%); frequent recurrence, 3 (20.0%); infrequent recurrence, 4 (26.7%). Among participants for whom a kidney biopsy was performed, nine INS patients exhibited minimal change, one INS patient had C1q nephropathy, and one INS patient had mesangial proliferative nephropathy. On the other hand, for IgAN, nine patients exhibited pathological changes in more than 80% of glomeruli and eight patients had crescent bodies in more than 30% of glomeruli.

Glucocorticoids were used as an initial treatment in all participants except one patient with IgAN (Table 1). Cyclosporine and mizoribine were the most common immunosuppressive agents used for INS, while mycophenolate mofetil (MMF) was less common because the use of MMF for INS was not covered by health insurance in Japan at that time. Rituximab, whose efficacy was confirmed by clinical trials in Japan, was also used in seven cases of INS [18]. In IgAN, however, methylprednisolone pulse therapy was administered in more than half of the cases. Mizoribine, which is recommended in Japan as a combination therapy, was the most commonly used immunosuppressive agent (Table 1) [19, 20]. Angiotensin-converting enzyme inhibitor (ACEI) and angiotensin 2 receptor blocker (ARB) were used in both INS and IgAN, but more frequently in IgAN.

The mean age of the participants included in this analysis was 23.9 years for INS and 24.2 years for IgAN, respectively. There were no significant differences in height, weight, BMI, or age between the two diseases (Table 2). The eGFR was predominantly higher in the INS group than in the IgAN group, but only one IgAN patient who had undergone a kidney transplant had an eGFR less than 60 mL/min/1.73 m2. Multiple regression analysis was conducted on final height, considering disease and gender, and utilizing clinical findings at the time of initial onset, number of recurrences, and treatment history as variables. A negative correlation was observed in the urinary protein creatinine ratio (U-TP/U-Cr ratio) at the time of initial onset (p = 0.027) (Fig. 2A). Additionally, it was evident that the group receiving MMF treatment had a significantly shorter height (p = 0.010), while no significant difference was observed with methylprednisolone pulse therapy or other immunosuppressive agents (Supplemental Fig. 1). It should be noted that MMF administration for INS was not covered by health insurance in Japan, which likely led to patients resorting to MMF because of difficulties in maintaining remission with other immunosuppressive agents. No significant correlation was found between final height and the number of recurrences. In addition, we conducted a multiple regression analysis on eGFR with the same variables (Fig. 2B, Supplemental Table 1). Serum Cr at onset showed a negative correlation with eGFR (p = 0.003).

Correlation between final height and clinical information. A Scatter plots showing the correlation between final height and U-TP/U-Cr ratio at initial onset. B Scatter plots showing the correlation between final eGFR and serum Cr at initial onset. Each dot shape indicates gender. Circle, female; triangle, male

When the questionnaire was administered, follow-up in pediatrics had been completed in all but one case (Table 2). Of the 37 patients, seven had discontinued treatment and hospital visits, and 30 had been transitioned to the adult department for ongoing follow-up. The expected age for transitioning to adult services in our institution is typically 18 years. Specifically, patients with INS or IgAN transition at 18 years old, usually upon high school graduation. Nevertheless, they have the option to continue their follow-up until they reach age 20 or complete their higher education if they wish. The mean follow-up in pediatrics was 9.8 years for INS and 7.0 years for IgAN, and the mean age of transition from pediatrics was 18.8 years for INS and 18.3 years for IgAN, respectively. Hence, we analyzed the age of transition using disease, gender, clinical findings at the time of initial onset, and the number of recurrences as variables. No significant difference was found between INS and IgAN, but a high number of recurrences was detected as being positively correlated with age at transition (Fig. 3). Of the 30 patients who continued treatment, 22 were transitioned to the adult department because of their age, and the remaining eight were transitioned because of stable disease status. Most of the patients were transferred to nephrology, although one IgAN patient with kidney failure who received a kidney transplant was followed in the transplant surgery department. None of the cases utilized a transition program when transferring from pediatrics to adult departments.

Correlation between age at transition and the number of recurrences. Participants were classified into seven groups according to the number of recurrences, and the association with age at transition was analyzed. Group 1, no recurrence; group 2, 1–5 times; group 3, 6–10 times; group 4, 11–15 times; group 5, 16–20 times; group 6, 21–25 times; group 7, 26–30 times

We also administered a survey on distress caused by glomerular disease in our questionnaires. Adverse effects from medications were identified as the most painful type of distress caused by glomerular disease (Fig. 4A). Of these, obesity, moon face, and hypertrichosis, which are appearance-related issues, were reported to be the most painful (Fig. 4B). Other issues, which were frequently mentioned in questionnaires, included swelling, recurrence and hospitalization, and restricted exercise and diet. Although it was frequently mentioned as an adverse effect of medication, impaired immunity and the risk of infection did not seem to have a significant impact on overall distress. Interestingly, many participants indicated that the impact on their school life was distressing.

Distress associated with glomerular disease. Scatterplots depicting A distress caused by glomerular diseases and B distress caused by adverse effects of medications. The size of each mark represents the number of responses

Next, we collected information on the impact on school life and higher education in the form of open-ended questions (Supplemental Table 2). The collected comments were then categorized and organized using the affinity diagram method, which is known as the KJ method [16, 17]. In this method, participant responses were initially extracted by factor. Similar factors were then aggregated, grouped, and given titles. Finally, we identified and visualized relationships, such as cause, effect, and modifiers, among the groups. The results obtained by the affinity diagram method are presented in Fig. 5. In categorizing the comments received from participants, negative impacts included the direct distress associated with glomerular disease and its treatment, the impact on school and learning, and stress in interpersonal relationships. The direct distress associated with glomerular disease and its treatment included infectious conditions and appearance changes caused by glucocorticoids and immunosuppressive agents. However, many participants (71.0%) mentioned the impacts of exercise restrictions and physical decline, which appeared to have a tremendous effect. Exercise restrictions and appearance changes affected patients’ formation of relationships with their surroundings, and a lack of sufficient understanding of patients’ symptoms and situation caused psychological distress. Additionally, apart from the impact of the disease on learning in school, increased absences because of hospital visits and hospitalization were frequently mentioned (23.7%). It was also indicated that they were unable to take the school examination itself due to their diseases. Furthermore, some participants indicated that it was challenging to continue seeing their primary facilities when they moved to distant locations. Conversely, positive impacts were also observed. Some participants’ comments suggested that their experience of having a glomerular disease and interactions with medical staff had a positive impact on their interest in medicine and their decision to pursue a medical career. These various impacts appeared to significantly contribute to some participants’ decision to pursue higher education. Importantly, the rate of engaging in higher education among participants in this study was significantly higher than the regional average in 2016 (https://www.e-stat.go.jp/dbview?sid=0000010105), which corresponds to the time at which participants were considering higher education (24 out of 36 [66.7%] vs. 7333 out of 15,622 [46.9%], p = 0.028). These findings suggest that various impacts associated with glomerular disease contribute to a high rate of advancement to higher education.

Affinity diagram of the impact of glomerular disease on school life and higher education. Blue bubbles: factors directly due to the disease or treatment; green bubbles: factors related to school life and learning; yellow bubbles: factors related to interpersonal relationships; pink bubbles: positive factors obtained due to the disease. The size of the bubbles indicates the number of answers obtained. Blue arrows, negative effect; pink arrows, positive effects