Pandemic and post-pandemic shifts in onset and severity of pediatric nephrotic syndrome: a comparative cohort analysis.

Background: Pediatric idiopathic nephrotic syndrome (INS) involves complex immunological mechanisms, and clinical presentation may be influenced by environmental factors and access to medical services. The impact of the COVID-19 pandemic on its clinical and evolutionary profile remains insufficiently characterized. Objectives: To compare pandemic and post-pandemic pediatric INS regarding demographic, clinical and biological characteristics and early disease evolution, and to explore factors associated with infection-related onset and corticosteroid response. Methods: Single-center retrospective study on 59 pediatric patients with INS, diagnosed during the pandemic (n=29) and post-pandemic (n=30) period, analyzing demographic, clinical, biological and therapeutic variables. Results: Patient distribution was similar between periods. Hospital stay was longer during the pandemic (median 10, IQR 5 vs. median 8, IQR 4; p = 0.015), whereas the interval from symptom onset to presentation did not differ significantly between periods. Infections associated with onset were less frequent during the pandemic compared to the post-pandemic period (31% vs. 60%; p=0.026), without differences in severity. Corticosteroid-response categories are reported descriptively because follow-up duration differed substantially between the two cohorts, limiting complete ascertainment of corticosteroid dependence in the post-pandemic group. A lower proportion of corticosteroid-sensitive patients was observed during the pandemic, while corticosteroid responsiveness was associated with time to remission (ρ = 0.439; p = 0.003). Exploratory logistic regression suggested that the post-pandemic period, anemia at diagnosis, and weight status were associated with infection-associated onset. In an exploratory logistic regression model, macroscopic hematuria was the only significant clinical variable associated with the observed corticosteroid response (p = 0.039). Biological parameters were similar between periods, except for higher fibrinogen (p = 0.021) and complement C4 (p = 0.034) levels during the pandemic. Exploratory descriptive analyses of the subgroup with available C4 measurements did not identify statistically significant associations between C4 levels and corticosteroid-response categories or other examined clinical characteristics. Conclusions: Children diagnosed during the pandemic experienced longer hospitalizations, whereas most demographic and biological characteristics were comparable between periods. Infection-associated onset was less frequent during the pandemic than during the post-pandemic period, whereas the number of diagnosed cases was similar between the two study periods. Complement C4 differed between the pandemic and post-pandemic cohorts, but exploratory descriptive analyses did not identify statistically significant associations between C4 levels and corticosteroid response or other examined clinical characteristics. Hematuria was associated with corticosteroid response, whereas anemia and weight status were associated with infection-related onset in exploratory analyses. However, these findings should be interpreted cautiously because of the limited sample size and require confirmation in larger prospective studies.