Pediatric Idiopathic Nephrotic Syndrome Across Two Eras: Lessons from the COVID-19 Pandemic and Beyond

Background: The COVID-19 pandemic has affected healthcare delivery worldwide, potentially influencing the presentation and management of pediatric idiopathic nephrotic syndrome (INS). Beyond healthcare-related factors, pandemic-associated environmental changes may have modified immune responses involved in disease onset and progression.

Objectives: To investigate differences in clinical presentation and immunological profile of pediatric INS diagnosed during and after the COVID-19 pandemic, with particular focus on factors associated with corticosteroid responsiveness.

Methods: A retrospective cohort study was performed in 59 children with newly diagnosed INS, including patients diagnosed during the pandemic (n=29) and post-pandemic period (n=30). Clinical, laboratory, and outcome data were analyzed using comparative and multivariable statistical models.

Results: Demographic characteristics and baseline nephrotic severity were comparable between groups. Patients diagnosed during the pandemic had longer hospital stays and tended to present later after symptom onset. While infections were less frequently associated with disease onset during the pandemic, overall disease severity remained similar. Among laboratory parameters, complement C4 and fibrinogen levels were significantly higher in children diagnosed during the pandemic, suggesting differences in immune and procoagulant activation. Corticosteroid responsiveness showed no significant variation between periods; however, reduced responsiveness was associated with delayed remission. Notably, complement C4 demonstrated a strong association with corticosteroid response patterns, whereas macroscopic hematuria emerged as a potential marker of unfavorable therapeutic outcome.

Conclusions: Although the pandemic did not substantially modify the clinical phenotype of pediatric INS, it was associated with distinct immunological features and changes in healthcare utilization. The observed relationship between complement C4 levels and corticosteroid responsiveness highlights a potential biomarker for early risk stratification and supports further investigation of complement-mediated mechanisms in pediatric nephrotic syndrome.