PDF(Pubmed)
Abstract：
Simultaneous inhibition of angiotensin II AT1 and endothelin ETA receptors has emerged as a promising approach for treatment of chronic progressive kidney disease. This therapeutic approach has been advanced by the introduction of sparsentan, the first dual AT1 and ETA receptor antagonist. Sparsentan is a single molecule with high affinity for both receptors. It is US Food and Drug Administration approved for immunoglobulin A nephropathy (IgAN) and is currently being developed as a treatment for rare kidney diseases, such as focal segmental glomerulosclerosis. Clinical studies have demonstrated the efficacy and safety of sparsentan in these conditions. In parallel with clinical development, studies have been conducted to elucidate the mechanisms of action of sparsentan and its position in the context of published evidence characterizing the nephroprotective effects of dual ETA and AT1 receptor inhibition. This review summarizes this evidence, documenting beneficial anti-inflammatory, antifibrotic, and hemodynamic actions of sparsentan in the kidney and protective actions in glomerular endothelial cells, mesangial cells, the tubulointerstitium, and podocytes, thus providing the rationale for the use of sparsentan as therapy for focal segmental glomerulosclerosis and IgAN and suggesting potential benefits in other renal diseases, such as Alport syndrome.
摘要：
同时抑制血管紧张素IIAT1和内皮素ETA受体已成为治疗慢性进行性肾脏疾病的有希望的方法。通过引入sparsentan，这种治疗方法得到了发展，第一个双AT1和ETA受体拮抗剂。Sparsentan是对两种受体都具有高亲和力的单分子。它是美国食品和药物管理局批准的免疫球蛋白A肾病（IgAN），目前正在开发作为治疗罕见的肾脏疾病，例如局灶节段性肾小球硬化。临床研究已经证明了sparsentan在这些病症中的有效性和安全性。在临床发展的同时，在已发表的表征ETA和AT1受体双重抑制的肾保护作用的证据的背景下，已经进行了研究以阐明sparsentan的作用机制及其位置。这篇综述总结了这一证据，记录有益的抗炎，抗纤维化,和sparsentan在肾脏中的血液动力学作用和对肾小球内皮细胞的保护作用，系膜细胞,肾小管间质，足细胞,从而提供了使用sparsentan治疗局灶性节段肾小球硬化和IgAN的理由，并提示了其他肾脏疾病的潜在益处。比如Alport综合征.
