From the Guidelines
Mineralocorticoid receptor antagonists (MRAs) are kidney protective because they block the harmful effects of aldosterone on the kidneys, reducing inflammation, fibrosis, and oxidative stress in kidney tissue, as demonstrated in the FIDELIO-DKD trial 1.
Key Mechanisms of MRAs
- MRAs prevent aldosterone from binding to mineralocorticoid receptors, which reduces protein leakage through the glomerular filtration barrier and lessens hemodynamic stress on the kidneys.
- They improve the effectiveness of other kidney-protective medications like ACE inhibitors and ARBs when used in combination.
- MRAs are particularly beneficial for patients with diabetic kidney disease, heart failure with reduced ejection fraction, or resistant hypertension who have proteinuria.
Clinical Evidence
- The FIDELIO-DKD trial 1 demonstrated a significant reduction in CKD progression and cardiovascular events in people with diabetes and advanced CKD.
- The trial had a primary end point of time to first occurrence of the composite end point of onset of kidney failure, a sustained decrease of eGFR >40% from baseline over at least 4 weeks, or renal death.
- MRAs have been shown to reduce albuminuria and improve kidney function in patients with CKD, as reported in the 2025 standards of care in diabetes 1.
Monitoring and Dosing
- Common dosing includes spironolactone 25-50 mg daily, eplerenone 25-50 mg daily, or finerenone 10-20 mg daily, with dose adjustments based on kidney function and potassium levels.
- When prescribing MRAs, it's essential to monitor serum potassium and kidney function regularly, especially during the first few weeks of treatment, as hyperkalemia is a potential side effect.
From the Research
Kidney Protection by MRA
The kidney protective effects of Mineralocorticoid Receptor Antagonists (MRAs) can be attributed to several factors:
- Reduction in proteinuria: Studies have shown that MRAs such as finerenone can reduce proteinuria in patients with diabetic kidney disease (DKD) 2, 3.
- Slowing of CKD progression: Finerenone has been shown to slow the progression of chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) 2, 3.
- Anti-inflammatory effects: MRAs have been found to have anti-inflammatory effects, which can help reduce the pathological overactivation of the mineralocorticoid receptor and inflammation that drive CKD progression 3.
- Blood pressure lowering: MRAs such as esaxerenone have been found to have blood pressure-lowering efficacy, which can help reduce the risk of CKD progression 3.
Mechanism of Action
The mechanism of action of MRAs involves the antagonism of the mineralocorticoid receptor, which can help reduce the effects of aldosterone on the kidney and heart. This can lead to a reduction in blood pressure, proteinuria, and CKD progression 4, 2, 3.
Clinical Evidence
Clinical trials have demonstrated the effectiveness of MRAs in patients with DKD. The FIDELIO-DKD and FIGARO-DKD trials, as well as the FIDELITY analysis, have shown that finerenone can have beneficial effects on the kidney and heart in patients with CKD and T2D 3. Additionally, studies have shown that MRAs such as spironolactone and eplerenone can be effective in reducing blood pressure and improving outcomes in patients with heart failure 5, 6.