Current and Future Therapeutics for Focal Segmental Glomerular Sclerosis in the Era of Precision Medicine: A Review.

Focal segmental glomerulosclerosis (FSGS) is not a single disease. Instead, it is a histopathological entity that is the manifestation of a wide range of clinical insults that injure the podocyte, a key structural element in the glomerular filtration barrier. The current classification of FSGS includes 4 subtypes: primary immune-mediated, genetic, secondary, and undetermined cause. Based on this scheme, patients are treated empirically with a combination of nonspecific renoprotective drugs and immunosuppressive agents in an effort to reduce proteinuria and preserve kidney function. However, there are no medications approved by the US Food and Drug Administration for FSGS. Moreover, current therapy is successful in achieving disease remission in less than a quarter of patients, and all of the available options are associated with significant side effects that limit their use in practice. Ongoing research using a full array of muti-omics analytical tools-including genomic, transcriptomic, proteomic, and metabolomic assessment-suggest that patients with FSGS can be characterized mechanistically by the primary process(es) initiating and promoting disease progression. This work is summarized in this review and raises the potential to individualize therapy for each patient with FSGS. This would usher in the potential for precision medicine to be applied in the treatment of those affected by this rare but serious glomerular disease.