Polenus Paula, Đuran Ana, Karanović Štambuk Sandra
School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.
Department of Pulmonology, University Hospital Center Split, 21000 Split, Croatia.
Biomedicines. 2025 Aug 26;13(9):2081. doi: 10.3390/biomedicines13092081.
Chronic kidney disease (CKD) is a global health challenge, marked by significant morbidity and mortality and a rising economic burden. Despite established therapies such as renin-angiotensin system (RAS) inhibitors and SGLT2 inhibitors, a substantial residual risk of CKD progression and cardiovascular events persists. This gap is largely attributed to the sustained overactivation of the mineralocorticoid receptors by aldosterone, a key driver of renal inflammation and fibrosis. This review aims to bridge the understanding between aldosterone's intricate pathophysiology and emerging therapeutic strategies designed to address this unmet clinical need. We discuss the physiological regulation of aldosterone synthesis and secretion, the phenomenon of aldosterone breakthrough under conventional RAS blockade and the diverse mechanisms through which aldosterone mediates kidney damage. We evaluate novel non-steroidal mineralocorticoid receptor antagonists, exemplified by finerenone, which demonstrate superior safety profiles and valid efficacy in reducing renal and cardiovascular outcomes in clinical trials. Additionally, we examine aldosterone synthase inhibitors as an upstream therapeutic approach to directly reduce aldosterone production. These novel agents represent promising avenues to mitigate residual risk and improve long-term outcomes for patients with CKD.
慢性肾脏病(CKD)是一项全球性的健康挑战,其特征为高发病率、高死亡率以及不断增加的经济负担。尽管有诸如肾素-血管紧张素系统(RAS)抑制剂和钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂等既定疗法,但CKD进展和心血管事件的大量残余风险依然存在。这一差距很大程度上归因于醛固酮对盐皮质激素受体的持续过度激活,醛固酮是肾脏炎症和纤维化的关键驱动因素。本综述旨在弥合醛固酮复杂病理生理学与旨在满足这一未满足临床需求的新兴治疗策略之间的理解差距。我们讨论醛固酮合成和分泌的生理调节、传统RAS阻断下醛固酮突破的现象以及醛固酮介导肾脏损伤的多种机制。我们评估以非奈利酮为代表的新型非甾体盐皮质激素受体拮抗剂,其在临床试验中显示出卓越的安全性和降低肾脏及心血管结局的有效疗效。此外,我们研究醛固酮合酶抑制剂作为直接减少醛固酮生成的上游治疗方法。这些新型药物代表了减轻残余风险和改善CKD患者长期结局的有前景的途径。