Introduction: In pediatric idiopathic nephrotic syndrome (NS), various immunological stimuli are known to trigger relapse. A number of studies demonstrated that whereas some kind of immunological stimuli such as a part of vaccination did not precipitate NS relapses significantly. However, to date, the major limitation of past study is the lack of evaluation from the time of initial NS onset and the heterogenous background of patients, such as concomitant use of steroids or immunosuppressive agents, resulting in a lack of uniformity. Methods: We conducted a multicenter prospective cohort study of children newly diagnosed with idiopathic NS between the ages of 6 months and 15 years old between 2021 and 2024 at the seventeen hospitals. Immunological stimuli-including fever 38 C, vaccination, anesthesia, and surgery-occurring within one year after the initial onset of NS were prospectively evaluated, and their association with NS relapse was analyzed. The day of each immunological stimuli was defined as day 0. We defined the interval from the onset of NS to the immunological stimulus as the pre-stimuli period, and the two time windows between 0 to + 7 and 0 to + 30 as the direct association periods involving immunological stimuli. The NS relapse rate was calculated using the person-month method. Immunological stimuli that occurred while patients were receiving corticosteroids or immunosuppressive agents were excluded from the analysis. Results: A total of 77 patients (male: female = 53: 24) were included, with a mean age at onset of 6. 2 years. Among 71 patients with steroidsensitive NS at onset (and 6 with steroid-resistant cases), a total of 207 immunological stimuli occurred during the first year after the onset of NS. After excluding 81 immunological stimuli that met the exclusion criteria, 126 were included in the analysis (consisted of 92 episodes of fever 38 C, 33 vaccinations, 1 anesthesia, and 0 surgeries). The breakdown of vaccinations was as follows: influenza vaccine, 21 times; Japanese encephalitis vaccine, 3 times; varicella vaccine, 3 times; mumps vaccine, 3 times; measles-rubella vaccine, 1 time; Coronavirus disease 2019 vaccine, 1 time; and diphtheria-tetanus toxoid vaccine, 1 time. As compared with the pre-stimuli period, the relapse rate of NS during the period between 0 to + 7 was significantly higher across all 126 stimuli (0. 02 vs. 0. 09 relapses per person-month, p = 0. 01) and 92 episodes of fever 38 C (0. 025 vs. 0. 11 relapses per person-month, p = 0. 01). Upon evaluation of the pre-vaccination period following the 33 vaccination events and the period between 0 to + 7, there was no significant difference in the relapse rate of NS (0. 014 vs. 0. 03 relapses per person-month, p = 0. 61). When stratified by the timing of immunological stimuli, the proportion of patients who experienced a relapse of NS within 7 days following any immunological stimulus or an episode of fever 38 C was significantly higher at 5-6 months after the initial onset of NS compared with within the first 4 months (0/35; 0% vs. 4/24; 16%; p = 0. 02, 0/27; 0% vs. 4/17; 24%; p = 0. 02). Conclusion: In children with idiopathic NS who are not receiving corticosteroids or immunosuppressants, fever 38 C appears to represent a significant risk factor for relapse. I have no potential conflict of interest to disclose. I did not use generative AI and AI-assisted technologies in the writing process.
Yu et al. (Wed,) studied this question.