Rakotoarison Agata, Kepinska Marta, Konieczny Andrzej, Władyczak Karolina, Janczak Dariusz, Hałoń Agnieszka, Donizy Piotr, Banasik Mirosław
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska 213, 50-367 Wrocław, Poland.
Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wroclaw, Poland.
J Clin Med. 2024 Oct 11;13(20):6056. doi: 10.3390/jcm13206056.
The endothelin system is reported to play a significant role in glomerular and tubulointerstitial kidney disease. In the kidney, endothelins are produced in mesangial cells and the glomerular basement membrane by the endothelium and podocytes. The endothelin system regulates glomerular function by inducing proliferation, increasing permeability and in effect proteinuria, and stimulating inflammation, tubular fibrosis, and glomerular scarring. Endothelin A receptor antagonists have been proven to delay the progression of chronic kidney disease and play a protective role in immunoglobulin A nephropathy, focal segmental glomerulosclerosis, and diabetic nephropathy. There are several ongoing research studies with ETAR antagonists in nondiabetic nephropathy, Alport disease, vasculitis and scleroderma nephropathy, which results are promising. Some reports suggest that the endothelin system might contribute to ischemia-reperfusion injury, acute graft rejection and deterioration of graft function. Endothelin inhibition in renal transplantation and its influence on graft survival is the future direction needing further research. The most frequent side effects associated with ETAR antagonists is fluid retention. Additionally, it should be considered if selective ETAR antagonists therapy needs to be co-administered with sodium-glucose co-transporter 2 inhibitors, renin-angiotensin-aldosterone inhibitors or diuretics and which patients should be recruited to such treatment to minimize the risk of adverse outcomes.
据报道，内皮素系统在肾小球和肾小管间质肾病中起重要作用。在肾脏中，内皮素由系膜细胞以及内皮细胞和足细胞产生于肾小球基底膜。内皮素系统通过诱导增殖、增加通透性以及实际上导致蛋白尿，并刺激炎症、肾小管纤维化和肾小球瘢痕形成来调节肾小球功能。内皮素A受体拮抗剂已被证明可延缓慢性肾脏病的进展，并在免疫球蛋白A肾病、局灶节段性肾小球硬化症和糖尿病肾病中发挥保护作用。目前有几项关于内皮素A受体拮抗剂在非糖尿病肾病、阿尔波特综合征、血管炎和硬皮病肾病中的研究正在进行，结果很有前景。一些报告表明，内皮素系统可能导致缺血再灌注损伤、急性移植物排斥反应和移植物功能恶化。肾移植中内皮素抑制及其对移植物存活的影响是需要进一步研究的未来方向。与内皮素A受体拮抗剂相关的最常见副作用是液体潴留。此外，还应考虑选择性内皮素A受体拮抗剂治疗是否需要与钠-葡萄糖协同转运蛋白2抑制剂、肾素-血管紧张素-醛固酮抑制剂或利尿剂联合使用，以及哪些患者应接受这种治疗以将不良后果的风险降至最低。
