Traditional, alternative, and emerging therapeutics for focal segmental glomerulosclerosis

Expert Opin Pharmacother. 2025 Jan 1. doi: 10.1080/14656566.2024.2446621. Online ahead of print.

Abstract

Introduction: Segmental focal glomerulosclerosis is a histological lesion characterized by podocyte damage. It may be a primary disease linked to an unknown circulating factor, secondary to viral infections, drug toxicity, or a disadaptive response to the loss of nephrons, or it may depend on gene mutations or have an indeterminate cause. The treatment of the primary form involves immunosuppressors. Additional pharmacotherapies for residual proteinuria are used, and emerging therapies are being studied to target other pathological pathways.

Areas covered: This paper covers the treatment of FSGS, focusing on traditional and emerging therapeutic strategies. It is based on the KDIGO 2021 guidelines and supplemented by a literature search conducted on PubMed.

Expert opinion: Treating FSGS is challenging due to its heterogeneity. Immunosuppression is adequate for primary FSGS but harmful in genetic or secondary forms. Key strategies include targeting the underlying cause and using agents that affect renal hemodynamics. Antifibrotic drugs can help slow kidney damage by addressing chronic inflammation and fibrosis. Alongside pharmacological treatments, managing blood pressure and restricting dietary salt are crucial. Finally, personalized treatment requires stratifying patients based on clinical, genetic, and histological data to improve clinical trial design and outcomes.

Keywords: Focal segmental glomerulosclerosis; calcineurin inhibitors; glucocorticoids; sodium-glucose cotransporter 2 inhibitors; sparsentan.

Publication types

  • Review