鹽皮質激素受體拮抗劑在慢性腎臟病的新進展

慢性腎臟病（chronic kidney disease, CKD）患者的鹽皮質激素受體（mineralocorticoid receptor, MR）的過度活化會造成體內鹽分、體液蓄積，進而造成高血壓；也會刺激腎臟、血管和心臟等器官的發炎反應而導致纖維化。這很可能是造成腎臟和心臟功能惡化的重要因素之一。因此，MR的阻斷是一個非常吸引人的治療方法。有不少的實驗室研究表明鹽皮質激素受體拮抗劑（mineralocorticoid receptor antagonists, MRAs）可以用於治療CKD和延緩其惡化。固醇類MRAs（spironolactone and eplerenone）已被發現對心臟衰竭病患有好處。然而，關於使用固醇類MRAs治療CKD的研究結果尚無定論。Finerenone為新一代的非固醇MRAs，和固醇類MRAs有許多不同之處。動物實驗中可以發現finerenone有比固醇類MRAs更好的益處／風險比。近幾年的大型隨機臨床試驗也表明finerenone在糖尿病和CKD病患有腎臟和心血管的好處。在這篇回顧中，我們闡述了MR的病生理機轉，並且探索固醇類MRAs在CKD和末期腎臟病（end-stage renal disease, ESRD）的效用和安全性。第二部分則是探討finerenone的特性和目前腎臟及心血管保護的臨床證據。

關鍵字

鹽皮質激素受體（Mineralocorticoid receptor, MR）；鹽皮質激素受體拮抗劑（Mineralocorticoid receptor antagonists, MRAs）； Finerenone ；慢性腎臟病（Chronic kidney disease）；心血管疾病（Cardiovascular disease）

並列摘要

Mineralocorticoid receptor (MR) overactivation in chronic kidney disease (CKD) patients causes sodium and fluid retention and provokes inflammation and fibrosis in kidney, blood vessels and heart. These processes may play an important role in progression of cardiorenal disease. Therefore, blockage of MR is an attractive therapeutic strategy. Several pre-clinical studies showed that mineralocorticoid receptor antagonists (MRAs) can treat CKD and retard its deterioration. Steroid MRAs (spironolactone and eplerenone) already showed benefits in patients with heart failure and refractory hypertension. However, the use of steroid MRAs in the treatment of CKD is currently inconclusive. Finerenone is a new, non-steroid MRA, with different molecular and pharmacokinetics from steroid MRAs. In animal study, finerenone has a more favorable benefit/risk ratio as compared with the steroid MRAs. In recent large randomized controlled trials, finerenone improved the renal and cardiovascular outcomes in type 2 diabetes and CKD patients. In this review, we describe the pathophysiology of MR and explore the efficacy and safety of steroid MRAs in CKD and end-stage renal disease (ESRD) patients. We then discuss the characteristics of finerenone and current clinical evidence in renal and cardiovascular protection.

並列關鍵字

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