Finerenone, under the brand name Kerendia, is indicated to lower the risk of eGFR decline, end stage kidney disease, cardiovascular death, heart attack, and hospitalization for heart failure in chronic kidney disease associated with type 2 diabetes. Finerenone is an oral drug that has been shown to help in reducing inflammation, fibrosis, and improving proteinuria, along with severe congestive heart failure and diabetic nephropathy. Finerenone is the only non steroidal MRA to be FDA approved, and it more selective and longer lasting compared to other MRAs, providing a dose dependent relationship over older MRAs. Finerenone is a non steroidal, or specific, mineralocorticoid receptor antagonist (MRA) that minimizes adverse effects such as hyperkalemia compared to non specific/steroidal MRAs. Binding of Finerenone to mineralocorticoid receptors (MRs) prevents the binding of coactivators of the MRs such as aldosterone, cortisol, and 11-deoxycorticosterone; preventing receptor activation. Aldosterone is a mineralocorticoid hormone responsible for contributing to the regulation of blood pressure, sodium reabsorption, and potassium excretion and therefore, plays a role in blood pressure via the RAAS pathway. In the principal cells of the collecting duct, sodium and water reabsorption occur, along with potassium excretion. The sodium channel (ENaC) transports Na+ from the tubule lumen into the principal cells, then the NA+/K+ ATPase pumps the Na+ into the interstitium where it reabsorbed into the blood. K+ ions are pumped into the principal cell from the interstitium via the Na+/K+ ATPase, then the K+ channel transports K+ from the cell into the lumen where it is excreted in urine. Water reabsorption is linked to Na+ reabsorption and occurs via the aquaporins. Activation of the RAAS system leads to increased production of aldosterone, which is produced by the adrenal cortex in the zone glomerulosa. Aldosterone acts on receptors in collecting and distal tubules of the nephron causing increased reabsorption of Na+ and increased secretion of K+. Aldosterone binds to mineralocorticoid receptors in the cytosol of the principal cells in the collecting duct. The mineralocorticoid receptors undergo dimerization and activation and move into the nucleus where they undergo transcription. Protein is then synthesized in the cytosol. This effect on gene transcription leads to an upregulation of sodium channels in the apical membrane and Na+/K+ ATPase in the basolateral membrane, aiding an increase in Na+ and water reabsorption and K+ excretion. This change in ion concentrations leads to an increased effective circulating volume. Aldosterone can also stimulate MRs in the heart. Once Finerenone binds to the MR, there is a protrusion of MR helix 12 which disables MR activation, therefore blocking the binding of aldosterone. By blocking the binding of aldosterone, the RAAS system. This prevents the aldosterone effects on gene transcription, therefore, there is a decrease in Na+ channels and Na+/K+ ATPase in the membrane. Sodium reabsorption decreases, the concentration of Na+ in the lumen becomes high and as a result, water reabsorption also decreases. The effects on Na+/K+ ATPase results in reduced K+ excretion. This effect of Finerenone is important for treating conditions like hypertension because the increased water excretion in urine leads to decreased blood plasma volume, lowering blood pressure. Finerenone has also been shown to be a therapeutic agent for patients with albuminuria, and to be responsible for decreased BNP levels. BNP is a hormone secreted by cardiomyocytes in heart ventricles in response to increased blood volume. Side effects of using oral Finerenone may include confusion, nausea and vomiting, nervousness, irregular heartbeat, stomach pain, and/or numbness/tingling in the hands, feet, and lips.

Finerenone Pathway References