Loss of normal kidney function affects more than 10% of the population and contributes to morbidity and mortality. Kidney diseases are currently treated with immunosuppressive agents, antihypertensives and diuretics with partial but limited success. Most kidney disease is characterized by breakdown of the glomerular filtration barrier (GFB). Specialized podocyte cells maintain the GFB, and structure–function experiments and studies of intercellular communication between the podocytes and other GFB cells, combined with advances from genetics and genomics, have laid the groundwork for a new generation of therapies that directly intervene at the GFB. These include inhibitors of apolipoprotein L1 (APOL1), short transient receptor potential channels (TRPCs), soluble fms-like tyrosine kinase 1 (sFLT1; also known as soluble vascular endothelial growth factor receptor 1), roundabout homologue 2 (ROBO2), endothelin receptor A, soluble urokinase plasminogen activator surface receptor (suPAR) and substrate intermediates for coenzyme Q10 (CoQ₁₀). These molecular targets converge on two key components of GFB biology: mitochondrial function and the actin–myosin contractile machinery. This Review discusses therapies and developments focused on maintaining GFB integrity, and the emerging questions in this evolving field.

失去正常肾功能影响超过 10% 的人口，并导致发病率和死亡率。目前用免疫抑制剂、抗高血压药和利尿剂治疗肾脏疾病，取得了部分但有限的成功。大多数肾脏疾病的特征是肾小球滤过屏障 (GFB) 的破坏。专门的足细胞维持GFB，足细胞与其他GFB细胞之间的结构-功能实验和细胞间通讯研究，结合遗传学和基因组学的进展，为直接干预GFB的新一代疗法奠定了基础。这些包括载脂蛋白 L1 (APOL1)、短瞬时受体电位通道 (TRPC)、可溶性 fms 样酪氨酸激酶 1 (sFLT1;₁₀ )。这些分子靶点集中在 GFB 生物学的两个关键组成部分：线粒体功能和肌动蛋白-肌球蛋白收缩机制。本综述讨论了专注于维持 GFB 完整性的疗法和发展，以及这一不断发展的领域中出现的问题。