Nephrotic Syndrome: an integrative review of etiological and pathophysiological aspects

Abstract

Introduction: Nephrotic syndrome is a clinical manifestation of glomerulopathies characterized by massive proteinuria, hypoalbuminemia, edema, and dyslipidemia, associated with structural alterations of the glomerular filtration barrier. Its etiological and pathophysiological heterogeneity poses diagnostic and therapeutic challenges, especially in light of recent advances in the identification of biomarkers and immunomodulatory therapies. Objective: To critically synthesize the scientific evidence published between 2013 and 2023 regarding the epidemiological, etiological, pathophysiological, clinical, and therapeutic aspects of nephrotic syndrome, highlighting diagnostic advances and implications for clinical practice. Methods: A systematic literature review was conducted according to PRISMA guidelines, searching the PubMed/MEDLINE, Scopus, Web of Science, Embase, and SciELO databases. Original articles, systematic reviews, clinical trials, and guidelines published between 2013 and 2023, in English, Portuguese, and Spanish, were included. After screening and applying eligibility criteria, 87 studies comprised the qualitative analysis. Discussion: The findings show that podocyte injury and immune-mediated mechanisms are central to the pathophysiology of the syndrome. The identification of specific autoantibodies, such as anti-PLA2R, has redefined the management of membranous nephropathy. Corticosteroids remain the initial therapy in many primary forms, although immunobiologicals have broadened therapeutic options, especially in resistant cases. Thromboembolic and infectious complications remain relevant prognostic determinants. Conclusion: Nephrotic syndrome has undergone significant conceptual evolution in the last decade, with advances in etiological stratification and personalized therapeutic approaches. The integration of molecular evidence and clinical practice is essential to optimize renal and systemic outcomes.