Division of Nephrology, Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
Pediatr Nephrol. 2009 Dec;24(12):2301-7. doi: 10.1007/s00467-009-1176-z. Epub 2009 Apr 4.
Much focus has been placed on the role of the renin-angiotensin system as a mediator of the progression of chronic kidney disease. Novel therapeutic strategies to inhibit the negative impact of renin-angiotensin activation, including dual therapy with an angiotensin-converting enzyme inhibitor and an angiotensin-receptor blocker, have been suggested to achieve more complete disruption of the renin-angiotensin system. The role played by aldosterone, a target of angiotensin II, in the progression of chronic kidney disease has become a subject of significant interest over the past decade. Experimental studies in animals have shown that persistently elevated aldosterone levels lead to pathohistological changes in the kidney, along with renal and cardiac fibrosis. Incomplete suppression of aldosterone may, therefore, contribute to the deleterious effects of the renin-angiotensin system in the setting of chronic kidney disease. Clinical trials in adults have shown a potential role for mineralocorticoid receptor blockers to delay further the development of end-stage renal disease by completing renin-angiotensin blockade. In adults, mineralocorticoid receptor blockade produces a significant anti-proteinuric effect and has minimal risk of causing hyperkalemia if the condition of the patients is closely monitored. Further studies will need to be conducted to determine whether mineralocorticoid receptor blockers are equally effective and safe for the treatment of chronic kidney disease in children.
人们非常关注肾素-血管紧张素系统在慢性肾脏病进展中的作用。新型治疗策略旨在抑制肾素-血管紧张素激活的负面影响,包括血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂的联合治疗,以更完全地阻断肾素-血管紧张素系统。过去十年中,醛固酮作为血管紧张素 II 的靶点在慢性肾脏病进展中的作用引起了极大的关注。动物实验研究表明,持续升高的醛固酮水平会导致肾脏的病理组织学变化,以及肾脏和心脏纤维化。醛固酮抑制不完全可能导致肾素-血管紧张素系统在慢性肾脏病中的有害作用。成人临床试验表明,醛固酮受体阻滞剂具有潜在作用,可通过完全阻断肾素-血管紧张素系统来延缓终末期肾病的进一步发展。在成人中,醛固酮受体阻滞剂可显著减少蛋白尿,且如果密切监测患者的病情,发生高钾血症的风险极小。需要进一步研究以确定醛固酮受体阻滞剂在儿童慢性肾脏病的治疗中是否同样有效和安全。