From the Guidelines
Non-steroidal mineralocorticoid receptor antagonists (MRAs) are not currently indicated for non-proteinuric renal disease. These medications, such as finerenone (Kerendia), have established benefits primarily in patients with chronic kidney disease (CKD) who have albuminuria, particularly in the context of type 2 diabetes 1. Finerenone is specifically approved for patients with CKD associated with type 2 diabetes who have an eGFR ≥25 mL/min/1.73m² and urine albumin-to-creatinine ratio (UACR) ≥30 mg/g, with the strongest evidence for those with UACR ≥300 mg/g. The medication works by blocking mineralocorticoid receptors, which reduces inflammation and fibrosis in kidney tissue. This mechanism differs from steroidal MRAs like spironolactone and eplerenone, which have greater effects on electrolyte handling.
Key Points to Consider
- The use of non-steroidal MRAs in non-proteinuric renal disease is not supported by current clinical guidelines and FDA approvals 1.
- Patients with non-proteinuric kidney disease should be managed with other evidence-based therapies appropriate for their specific condition and risk factors.
- The KDIGO 2022 clinical practice guideline recommends the use of nonsteroidal mineralocorticoid receptor antagonists for patients with T2D, an eGFR ≥25 ml/min per 1.73 m², normal serum potassium concentration, and albuminuria (≥30 mg/g [≥3 mg/mmol]) despite maximum tolerated dose of RAS inhibitor (RASi) 1.
- The choice of a nonsteroidal MRA should prioritize agents with documented kidney or cardiovascular benefits, and patients should be monitored regularly for serum potassium levels to mitigate the risk of hyperkalemia 1.
Clinical Implications
- Non-steroidal MRAs should not be used as a first-line treatment for non-proteinuric renal disease.
- Patients with CKD and albuminuria should be considered for treatment with non-steroidal MRAs, such as finerenone, in addition to other evidence-based therapies 1.
- The use of non-steroidal MRAs in clinical practice should be guided by the most recent and highest quality evidence, and patients should be closely monitored for potential adverse effects, such as hyperkalemia 1.
From the FDA Drug Label
For the treatment of hypertension: • Type 2 diabetes with microalbuminuria ( 4) • Serum creatinine >2.0 mg/dL in males, >1.8 mg/dL in females ( 4) • Creatinine clearance <50 mL/min ( 4)
The indication for eplerenone in non-proteinuric renal disease is not explicitly stated. However, the presence of a contraindication for serum creatinine >2.0 mg/dL in males and >1.8 mg/dL in females, and creatinine clearance <50 mL/min, suggests that the drug may be used with caution in patients with renal impairment, but only in the context of proteinuric renal disease (microalbuminuria).
- The FDA label does not provide direct information on the use of non-steroidal MRAs in non-proteinuric renal disease.
- Therefore, no conclusion can be drawn regarding the indication of non-steroidal MRAs in non-proteinuric renal disease 2.
From the Research
Non-Steroidal MRAs in Non-Proteinuric Renal Disease
- The provided studies do not directly address the use of non-steroidal MRAs in non-proteinuric renal disease 3, 4, 5, 6, 7.
- Most of the studies focus on the effectiveness of non-steroidal MRAs in patients with diabetic kidney disease (DKD) or proteinuric patients with DKD 3, 4, 5, 7.
- There is limited information on the use of non-steroidal MRAs in non-proteinuric renal disease, and more research is needed to determine their effectiveness in this population.
Available Data on Non-Steroidal MRAs
- Finerenone, a non-steroidal MRA, has been shown to slow CKD progression and reduce cardiovascular morbidity and mortality in patients with DKD 3, 4, 7.
- Esaxerenone, another non-steroidal MRA, has been licensed in Japan for treating hypertension and has shown blood pressure-lowering efficacy 3, 5.
- Non-steroidal MRAs have been found to have a better benefit-risk ratio than steroidal MRAs, with a lower risk of hyperkalaemia 6, 7.
Future Research Directions
- Further studies are needed to investigate the effectiveness of non-steroidal MRAs in non-proteinuric renal disease 3, 4, 5, 6, 7.
- Research should focus on the potential benefits and risks of using non-steroidal MRAs in this population, including their effects on kidney function, cardiovascular outcomes, and hyperkalaemia risk.