Immune mechanisms and immunomodulatory therapies in steroid-resistant nephrotic syndrome

Abstract

Steroid-resistant nephrotic syndrome (SRNS) is a complex and refractory kidney disease generally causing chronic kidney dysfunction, characterized by persistent proteinuria despite prolonged corticosteroid therapy. This review comprehensively explores the mechanisms of immunity driving SRNS, mainly focusing on the complex function network within immune cells, pro-inflammatory cytokines, and podocyte injury. Current immunosuppressive therapies show limited efficacy, prompting exploration of precision immunomodulatory strategies. Emerging approaches include IL-17 or low-dose IL-12 modulation, proteasome or CD38 blockade, C5/factor B inhibition, and Rho kinase or caspase inhibition. Additionally, personalized strategies leveraging genetic profiling and biomarker-guided therapies are advancing tailored interventions. These targeted therapies address SRNS heterogeneity while minimizing systemic immunosuppression, offering new promise for halting disease progression. Future directions emphasize combinatorial regimens and mechanistic stratification to optimize therapeutic outcomes.

Keywords: Immune mechanisms; Immunomodulation; Nephrotic syndrome; Pathogenesis; Podocyte.