礦物皮質素受體拮抗劑與慢性腎臟病

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.