Page 87 - GPD-1-2

Gene & Protein in Disease Diagnosis and treatment of aldosterone-related diseases

antagonists (MRAs) can competitively bind to MR with and potassium excretion in the epithelial cells of the distal
ALD, thus inhibiting the effect of ALD, and subsequently nephron, thereby maintaining the stability of the electrolyte
improving blood pressure . At present, steroidal MRAs homeostasis. In this case, it plays a key role in maintaining
[35]
(spironolactone and eplerenone) are widely available, a constant extracellular volume and regulating blood
and the third-generation non-steroidal MRA, which will pressure. Studies have shown that it also has a significant
benefit patients with hypertension and aldosteronism, is effect on cardiovascular disease, but its mechanism of
[42]
now also in the clinical stage. action needs to be further studied . As a new generation
of non-steroidal antagonists, its steroidal structure endows
4.1. First-generation MRA: spironolactone it with high selectivity and affinity for MR, allowing it to
When sodium ion content in the body decreases or overcome the adverse effects of hyperkalemia associated
potassium ion content increases, the secretion of with spironolactone and eplerenone (Table 1) as well as
aldosterone will be stimulated. However, the sensitivity achieve maximum cardiovascular activity. The findings
to potassium ion content is higher compared to sodium from animal experiments have revealed that finerenone
ions. The increase of serum potassium by 0.1 mmol/L can can effectively protect the heart and kidney.
[36]
stimulate the secretion of aldosterone . Spironolactone is In terms of clinical research, the results of clinical
the first-generation of synthetic steroid-based MRA, and its Phase I trials have shown that MR antagonists are well
chemical structure is similar to that of aldosterone. It binds absorbed in vivo. Pharmacokinetic studies have found that
to MRA non-selectively, so that the K and Na exchange finerenone has an effect when its plasma concentration
+
+
across the membrane of the distal convoluted tubule and reaches 5–20 ng/mL. It has high oral availability, reaching
collecting duct is blocked, and Na excretion is increased, about 40%, with a half-life of 15 h. Its average plasma
+
thus lowering blood pressure [35,37] . Other than binding concentration reaches a peak after 1-3 h following oral
to MRs, spironolactone can also bind to glucocorticoid administration. In the clinical Phase II trial, 764 patients
receptors. Hence, there are certain side effects with its with diabetic nephropathy were observed for 60 days, and
use, such as male impotence, sexual dysfunction, and it was found that there was no difference in adverse effects
masculinization caused by the decrease of progesterone, between the 10 mg/day finerenone group and the placebo
testosterone, and other sex hormones. However, these side group compared with the control group. In the 2015
effects will resolve on withdrawal [38,39] . Annual Report of the European Society of Cardiology, it
was reported that finerenone plays a role in improving heart
4.2. Second-generation MRA: eplerenone failure caused by Type 2 diabetes or chronic kidney disease
A new generation of selective aldosterone antagonist, to a certain extent. Phase III clinical trials have shown that
eplerenone, was developed by Pfizer-Pharmacia under the finerenone is safe and effective and can effectively reduce
trade name Inspra and was first marketed in the United the incidence of hyperkalemia; it helps maintain a good
States in 2002 . Eplerenone is a selective MRA with a hemodynamic effect and contributes to the prognosis of
[38]
long half-life and good tolerance. It only binds to MRs patients [39-42] .
and has low affinity for receptors such as androgen and 5. Summary and prospect
progesterone; thus, it can reduce the side effects caused
by the first-generation MRA and be used in the treatment Aldosterone is an important steroid hormone among
of heart failure and hypertension following myocardial mineralocorticoids. It is difficult to detect aldosterone
infarction [35,36] . According to a study, the combined use accurately because its content in blood ranges in units
of eplerenone and standard treatment drugs reduced as low as pg/mL. CLIA addresses the limitations of
the total mortality rate of the treatment group with radioimmunoassay and enables the simultaneous detection
heart failure following acute myocardial infarction by of renin and aldosterone concentrations; nevertheless, it is
15% (P = 0.008) . unable to solve the cross-reaction problem. In addition,
[35]
reducing costs and improving the research and application
4.3. Third-generation of MRA: finerenone of equipment and imported reagents are also major issues
Finerenone is an oral non-steroidal MRA, discovered to be solved. The stability of the test data of the emerging
by Bayer in Germany. It is based on the previous two liquid chromatography technology in clinical diagnosis
generations. Finerenone can block the adverse effects and its correlation with RIA and CLIA should also be
caused by excessive activation of MRs caused by ascertained to determine the best entry point for the
aldosterone. It has shown a significant curative effect on detection and diagnosis of this method.
chronic heart failure and chronic kidney disease [40,41] . Its In recent years, the number of patients with
mechanism of action involves the maintenance of sodium metabolic diseases caused by abnormal aldosterone

Volume 1 Issue 2 (2022) 5 https://doi.org/10.36922/gpd.v1i2.136