{"title":"在荚膜细胞损伤和糖尿病肾病中靶向内皮素信号转导。","authors":"Maulana Antiyan Empitu, Pranindya Rinastiti, Ika Nindya Kadariswantiningsih","doi":"10.1007/s40620-024-02072-w","DOIUrl":null,"url":null,"abstract":"<p><p>Despite advances in diabetes management, there is an urgent need for novel therapeutic strategies since the current treatments remain insufficient in halting the progression of diabetic nephropathy-diabetic kidney disease (DN-DKD). This review is mainly addressed on the pivotal role of endothelin-1 in the pathophysiology of DN, with a specific focus on its effects on podocytes and the glomerular filtration barrier. Endothelin-1 promotes mesangial cell proliferation, sclerosis, and direct podocyte injury via the activation of endothelin type A and B receptors, that drive the progression of glomerulosclerosis in DN-DKD. Endothelin receptor antagonists, including drugs like atrasentan and sparsentan, have demonstrated nephroprotective effects in experimental models by reducing proteinuria and podocyte injury. The therapeutic potential to slow the progression of DN to end-stage kidney disease (ESKD) of these endothelin receptor antagonists in clinical practice is currently under evaluation. However, fluid retention and increased risk of heart failure associated with endothelin receptor antagonists need careful consideration. This review aims to provide an in-depth analysis of the pathophysiological role of endothelin and the emerging therapeutic implications of targeting this pathway in DN-DKD and discusses efficacy, safety, and the possibility of combining the new generation of endothelin receptor antagonists with the standard treatment of CKD and DN-DKD.</p>","PeriodicalId":16542,"journal":{"name":"Journal of Nephrology","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Targeting endothelin signaling in podocyte injury and diabetic nephropathy-diabetic kidney disease.\",\"authors\":\"Maulana Antiyan Empitu, Pranindya Rinastiti, Ika Nindya Kadariswantiningsih\",\"doi\":\"10.1007/s40620-024-02072-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Despite advances in diabetes management, there is an urgent need for novel therapeutic strategies since the current treatments remain insufficient in halting the progression of diabetic nephropathy-diabetic kidney disease (DN-DKD). This review is mainly addressed on the pivotal role of endothelin-1 in the pathophysiology of DN, with a specific focus on its effects on podocytes and the glomerular filtration barrier. Endothelin-1 promotes mesangial cell proliferation, sclerosis, and direct podocyte injury via the activation of endothelin type A and B receptors, that drive the progression of glomerulosclerosis in DN-DKD. Endothelin receptor antagonists, including drugs like atrasentan and sparsentan, have demonstrated nephroprotective effects in experimental models by reducing proteinuria and podocyte injury. The therapeutic potential to slow the progression of DN to end-stage kidney disease (ESKD) of these endothelin receptor antagonists in clinical practice is currently under evaluation. However, fluid retention and increased risk of heart failure associated with endothelin receptor antagonists need careful consideration. This review aims to provide an in-depth analysis of the pathophysiological role of endothelin and the emerging therapeutic implications of targeting this pathway in DN-DKD and discusses efficacy, safety, and the possibility of combining the new generation of endothelin receptor antagonists with the standard treatment of CKD and DN-DKD.</p>\",\"PeriodicalId\":16542,\"journal\":{\"name\":\"Journal of Nephrology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-09-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Nephrology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40620-024-02072-w\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nephrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40620-024-02072-w","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
尽管糖尿病治疗取得了进展,但由于目前的治疗方法仍不足以阻止糖尿病肾病(DN-DKD)的发展,因此迫切需要新的治疗策略。本综述主要探讨内皮素-1 在糖尿病肾病病理生理学中的关键作用,并特别关注其对荚膜细胞和肾小球滤过屏障的影响。内皮素-1 通过激活 A 型和 B 型内皮素受体促进系膜细胞增殖、硬化和荚膜细胞直接损伤,从而推动 DN-DKD 肾小球硬化的进展。内皮素受体拮抗剂,包括阿曲生坦(astrasentan)和斯帕生坦(sparsentan)等药物,通过减少蛋白尿和荚膜细胞损伤,在实验模型中显示出肾脏保护作用。目前正在对这些内皮素受体拮抗剂在临床实践中延缓 DN 向终末期肾病(ESKD)进展的治疗潜力进行评估。然而,与内皮素受体拮抗剂相关的体液潴留和心力衰竭风险增加问题需要慎重考虑。本综述旨在深入分析内皮素的病理生理作用以及针对 DN-DKD 这一通路的新兴治疗意义,并讨论新一代内皮素受体拮抗剂的疗效、安全性以及与 CKD 和 DN-DKD 标准治疗相结合的可能性。
Targeting endothelin signaling in podocyte injury and diabetic nephropathy-diabetic kidney disease.
Despite advances in diabetes management, there is an urgent need for novel therapeutic strategies since the current treatments remain insufficient in halting the progression of diabetic nephropathy-diabetic kidney disease (DN-DKD). This review is mainly addressed on the pivotal role of endothelin-1 in the pathophysiology of DN, with a specific focus on its effects on podocytes and the glomerular filtration barrier. Endothelin-1 promotes mesangial cell proliferation, sclerosis, and direct podocyte injury via the activation of endothelin type A and B receptors, that drive the progression of glomerulosclerosis in DN-DKD. Endothelin receptor antagonists, including drugs like atrasentan and sparsentan, have demonstrated nephroprotective effects in experimental models by reducing proteinuria and podocyte injury. The therapeutic potential to slow the progression of DN to end-stage kidney disease (ESKD) of these endothelin receptor antagonists in clinical practice is currently under evaluation. However, fluid retention and increased risk of heart failure associated with endothelin receptor antagonists need careful consideration. This review aims to provide an in-depth analysis of the pathophysiological role of endothelin and the emerging therapeutic implications of targeting this pathway in DN-DKD and discusses efficacy, safety, and the possibility of combining the new generation of endothelin receptor antagonists with the standard treatment of CKD and DN-DKD.
期刊介绍:
Journal of Nephrology is a bimonthly journal that considers publication of peer reviewed original manuscripts dealing with both clinical and laboratory investigations of relevance to the broad fields of Nephrology, Dialysis and Transplantation. It is the Official Journal of the Italian Society of Nephrology (SIN).