Altered Sphingolipids, Glycerophospholipids, and Lysophospholipids Reflect Disease Status in Idiopathic...

Idiopathic steroid-sensitive nephrotic syndrome (ISSNS) is the most common glomerular disease in children, yet its molecular mechanisms and lipid-mediated pathophysiology remain poorly understood. In this study, we performed comprehensive non-targeted metabolomic analysis of serum samples obtained from children with ISSNS during both the nephrotic and remission phases to identify metabolic alterations associated with disease status. Using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS), we profiled low-molecular-weight metabolites and identified significant alterations in several lipid classes, including sphingolipids, glycerophospholipids, and lysophospholipids. Several sphingomyelin and phosphatidylcholine species showed strong correlations with total cholesterol levels, reflecting lipid alterations consistent with the hyperlipidemic state that characterizes ISSNS. In contrast, oxidized phosphatidylcholines may more specifically reflect oxidative membrane injury and glomerular permeability changes associated with disease status. These findings highlight membrane lipid remodeling as a key feature of active disease and suggest potential lipid-based biomarkers for disease monitoring and therapeutic evaluation in pediatric ISSNS. This study provides a metabolomic framework for understanding lipid-driven mechanisms of ISSNS pathophysiology.