Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Division of Nephrology, University of Utah Health, Salt Lake City, Utah, USA.
Curr Opin Nephrol Hypertens. 2021 Jul 1;30(4):456-465. doi: 10.1097/MNH.0000000000000716.
To summarize new clinical findings of endothelin receptor antagonists (ERA) in various etiologies of kidney disease targeted in clinical trials.
Endothelin-1 is a multifunctional peptide with potential relevance to glomerular and tubulointerstitial kidney diseases. The phase 3 SONAR trial demonstrated a significant reduction in clinically relevant kidney outcomes for patients with diabetic kidney disease (DKD) after long-term treatment with the ERA, atrasentan, in addition to blockade of the renin-angiotensin-aldosterone system. Promising preclinical disease models and small clinical trials in non-DKD resulted in the initiation of phase 3 trials investigating the effects of long-term treatment with ERA in patients with immunoglobulin A (IgA) nephropathy and focal segmental glomeruloscelerosis (FSGS). The mechanisms by which ERA protects the kidneys have been extensively studied with evidence for the protection of tubule cells, podocytes, mesangial cells, the endothelial glycocalyx, and a reduction in glomerular perfusion pressure. The occurrence of fluid retention during ERA treatment, particularly in susceptible populations, necessitates strategies to support safe and effective treatment.
Treatment with ERA induces long-term kidney protection in DKD. Phase 3 trials are underway to investigate ERA effects in patients with IgA nephropathy and FSGS.
总结临床试验中针对不同病因肾脏病的内皮素受体拮抗剂（ERA）的新临床发现。
内皮素-1 是一种多功能肽，可能与肾小球和肾小管间质肾脏疾病有关。3 期 SONAR 试验表明，长期接受 ERA（阿曲生坦）治疗的糖尿病肾病（DKD）患者的临床相关肾脏结局显著减少，除了阻断肾素-血管紧张素-醛固酮系统外。在非 DKD 中，有前景的临床前疾病模型和小型临床试验导致启动了 3 期临床试验，以研究长期接受 ERA 治疗在 IgA 肾病和局灶节段性肾小球硬化症（FSGS）患者中的效果。已经广泛研究了 ERA 保护肾脏的机制，有证据表明它可以保护肾小管细胞、足细胞、系膜细胞、内皮糖萼，并降低肾小球灌注压。在 ERA 治疗期间，特别是在易感人群中，会出现液体潴留，这需要采取策略来支持安全有效的治疗。
ERA 治疗可诱导 DKD 的长期肾脏保护。正在进行 3 期临床试验，以研究 ERA 在 IgA 肾病和 FSGS 患者中的作用。
