ASSOCIATION BETWEEN IMMUNOLOGICAL STIMULI AND RELAPSE OF NEPHROTIC SYNDROME IN CHILDREN: A MULTICENTER PROSPECTIVE COHORT STUDY

 

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https://storage.unitedwebnetwork.com/files/1099/19288aeb334b15a6debb139879d2a1a8.pdf
ASSOCIATION BETWEEN IMMUNOLOGICAL STIMULI AND RELAPSE OF NEPHROTIC SYNDROME IN CHILDREN: A MULTICENTER PROSPECTIVE COHORT STUDY

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Shingo
Ishimori
Shingo Ishimori shingo-i0324os@live.jp Kobe University Graduate School of Medicine Department of Pediatrics Kobe Japan *
Shinya Ishiko shinya.ishiko@gmail.com Takatsuki General Hospital Department of Pediatrics Takatsuki Japan -
Yoshitsugu Kaku y_kaku@nifty.com Fukuoka Children’s Hospital Division of Nephrology Fukuoka Japan -
Koichi Kamei kamei-k@ncchd.go.jp National Center for Child Health and Development Division of Nephrology and Rheumatology Tokyo Japan -
Kenji Ishikura lxkenzo@gmail.com Kitasato University School of Medicine Department of Pediatrics Sagamihara Japan -
Taishi Nada nada.tai.jm@yokohama-cu.ac.jp Yokohama City University Medical Center Department of Pediatrics Yokohama Japan -
Yuko Shima yukotk@wakayama-med.ac.jp Wakayama Medical University Department of Pediatrics Wakayama Japan -
Hiroshi Kaito hskaitou_kch@hp.pref.hyogo.jp Hyogo Prefectural Kobe Children’s Hospital Department of Nephrology Kobe Japan -
Tomoko Horinouchi tohori@med.kobe-u.ac.jp Kobe University Graduate School of Medicine Department of Pediatrics Kobe Japan -
Keita Nakanishi ypyhc881@yahoo.co.jp Saiseikai-Hyogo Hospital Department of Pediatrics Kobe Japan -
Naohiro Kamiyoshi naohirokamiyoshi@yahoo.co.jp Himeji Red Cross Hospital Department of Pediatrics Himeji Japan -
Toshinori Minato toshinori-minato@toyookahp-kumiai.or.jp Hyogo Prefectural Toyooka Hospital Department of Pediatrics Toyooka Japan -
Rika Fujimaru rikafujimaru@gmail.com Osaka City General Hospital Division of Endocrinology, Metabolism and Nephrology Osaka Japan -
Kandai Nozu nozu@med.kobe-u.ac.jp Kobe University Graduate School of Medicine Department of Pediatrics Kobe Japan -
 

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.

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.

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 steroid-sensitive 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).

In children with idiopathic NS who are not receiving corticosteroids or immunosuppressants, fever ≥38°C appears to represent a significant risk factor for relapse.

Kewords