Novel Therapies in APOL1-Mediated Kidney Disease: From Molecular Pathways to Therapeutic Options

Apolipoprotein L1 (APOL1) high-risk variants confer an increased risk for the development and progression of kidney disease among individuals of recent African ancestry. Over the past several years, significant progress has been made in understanding the pathogenesis of APOL1-mediated kidney diseases (AMKD), including genetic regulation, environmental interactions, immunomodulatory, proinflammatory and apoptotic signaling processes, as well as the complex role of APOL1 as an ion channel. Collectively, these findings have paved the way for novel therapeutic strategies to mitigate APOL1-mediated kidney injury. Precision medicine approaches are being developed to identify subgroups of AMKD patients who may benefit from these targeted interventions, fueling hope for improved clinical outcomes. This review summarizes key mechanistic insights in the pathogenesis of AMKD, emergent therapies, and discusses future challenges.