礦物皮質素受體拮抗劑與慢性腎臟病

Mineralocorticoid Receptor Antagonists in Chronic Kidney Disease

劉志翰(Chih-Han Liu) ； 王一(Yi Wang) ； 李隆志(Lung-Chih Lee) ； 陳德全(Te-Chuan Chen) ； 邱鼎育(Ting-Yu Chiou) ； 李文欽(Wen-Chin Lee) ； 李建德(Chien-Te Lee)

《內科學誌》 33卷5期 (2022/10) Pp. 355-364

https://doi.org/10.6314/JIMT.202210_33(5).04

摘要

礦物皮質素受體分布於許多器官如心臟或腎臟，並藉由礦物質類固醇活化，主要生理功能可分為調控腎小管及透過其他非腎小管的組織造成影響。腎小管主要作用是維持電解質平衡及調控血壓。另一方面，礦物皮質素受體過度活化會導致發炎反應、氧化壓力增加及促進纖維化接續引起心血管系統及腎臟的損傷包含心肌肥大、心室重塑、心肌缺血、腎絲球增大及腎絲球硬化等。礦物皮質素受體拮抗劑（MRA）可以防止及減緩心臟腎臟的發炎反應及氧化壓力進而改善纖維化與硬化。現今MRA已用在接受標準治療下有症狀慢性心衰竭患者來改善長期預後。使用傳統型的MRA雖有降低蛋白尿的效果但因會增加高血鉀的機率，因此臨床上並不是治療慢性腎臟病患者的第一線用藥。近年來MRA的發展包括有第二代固醇類及新型非固醇類MRA上市，在降低蛋白尿都有不錯的效果，而更重要的是傳統的副作用如高血鉀、男性女乳症等內分泌異常都減少許多，最新臨床研究發現finerenone加在已使用醛固酮系統阻斷劑（RAS blockade）的糖尿病患者，具有延緩腎功能惡化及減少心血管死亡率的好處，且高血鉀機率與對照組相當。藉由阻斷礦物皮質素受體過度活化造成的心血管及腎臟疾病，這類新型MRA具有更廣泛臨床運用性及較少高血鉀及其他副作用的優勢。

關鍵字

慢性腎臟病（Chronic kidney disease） ； 礦物皮質素受體拮抗劑（Mineralocorticoid receptor antagonists） ； 蛋白尿（Proteinuria） ； 高血鉀（Hyperkalemia）

並列摘要

Mineralocorticoid receptor (MR) is a nuclear receptor that exists in many organs, such as the heart and kidney which can be activated by mineralocorticoids. The pathophysiological function of MR can be divided into tubular effects and non-tubular effects. The principal function on connecting tubule and collecting duct is balancing sodium/ potassium and maintaining blood pressure. On the other hand, over-activation of MR induces inflammation, increases oxidative stress and tissue fibrosis which subsequently induces cardiovascular and renal injury with resultant myocardial hypertrophy, ventricular remodeling, myocardial ischemia, glomerular hypertrophy and glomerulosclerosis. MR antagonist (MRA) can prevent and reduce inflammation and oxidative stress, thereby improve fibrosis and sclerosis. Currently, MRA is indicated in patients with symptomatic chronic heart failure under standard care to further improve long-term outcome. Traditional MRA also is able to reduce proteinuria but with increased hyperkalemia which excludes it as a first line therapy of chronic kidney disease (CKD).Recently, the second generation of steroid MRA and non-steroid MRA have been developed and both had greater effect on proteinuria decrease with less side effect such as hyperkalemia, gynecomastia or endocrine abnormalities. The clinical trial of finerenone add-on RAS inhibition therapy has showed the benefits in patients with diabetes on their CKD progression and improvement in cardiovascular mortality. The risk of hyperkalemia was comparable to control group. By blocking the over-activation of MR in cardiovascular and renal disease, the new MRA has the advantages in increasing its application on more patients and less risks of hyperkalemia and other side effects.