B7-1 and PD-L1 crosstalk in podocyte injury: from molecular mechanisms to novel therapeutic strategies for nephrotic syndrome

Nephrotic syndrome (NS) is a clinical condition characterized by substantial proteinuria, and its global incidence is increasing. Current treatment strategies mainly rely on glucocorticoids and immunosuppressants. Nevertheless, a proportion of patients may develop steroid resistance or suffer from disease relapse. Podocyte injury plays a central role in the pathogenesis of proteinuria in NS. Recent studies have increasingly highlighted the significance of the immune checkpoint molecules B7-1 and PD-L1 in podocytes, particularly their cis-interaction on the podocyte surface. This review systematically elaborates on the molecular basis, mechanisms of action, and the mechanisms underlying cis-interaction, as well as recent advances in targeted therapies involving B7-1 and PD-L1. It offers new perspectives for precision immunotherapy in NS, thereby promoting the translation of mechanistic insights into clinical applications. However, significant controversies remain regarding authentic B7-1 expression in podocytes, the strength of evidence for the PD-L1/B7-1 cis‑interaction in kidney disease, and the translational gaps between animal models and human NS. This review critically discusses these unresolved issues and outlines priority directions for future research.