Clinical bottom line
Novel oral nonsteroidal mineralocorticoid receptor antagonists (MRAs) represent a promising therapeutic option for patients with resistant hypertension complicated by chronic kidney disease (CKD). These agents offer potentially improved selectivity and safety profiles compared to traditional steroidal MRAs, which may translate into better blood pressure control with reduced risk of hyperkalemia and renal adverse effects. Current evidence, though still emerging, suggests these agents warrant consideration as adjunctive therapy in resistant hypertension among CKD patients, especially those intolerant to or inadequately controlled by conventional treatments.
What the evidence shows
Mineralocorticoid receptor antagonists have long been recognized for their efficacy in reducing blood pressure and providing cardioprotective and renoprotective effects in CKD and resistant hypertension (Duprez et al., 2018; Bakris et al., 2020). However, traditional steroidal MRAs such as spironolactone and eplerenone are limited by adverse effects including hyperkalemia and hormonal side effects, which restrict their use in advanced CKD.
Recent developments have introduced selective nonsteroidal MRAs, such as finerenone, which exhibit higher receptor selectivity and reduced off-target effects (Sueta et al., 2020; Kolkhof et al., 2015). These agents have demonstrated efficacy in lowering blood pressure and albuminuria in CKD patients, with a more favorable safety profile regarding potassium homeostasis and renal function (Iatridi et al., 2026). For example, finerenone has shown promise in reducing cardiovascular and renal events in diabetic kidney disease, a population often burdened by resistant hypertension (Iatridi et al., 2026).
Moreover, nonsteroidal MRAs may provide benefits in heart failure with preserved ejection fraction (HFpEF), a condition frequently coexisting with resistant hypertension and CKD, further supporting their therapeutic potential (Duprez et al., 2018). The improved pharmacokinetic and pharmacodynamic properties of these agents allow for once-daily dosing and better tolerability, which may enhance adherence in complex CKD populations.
Caveats and uncertainty
Despite encouraging data, the evidence base for nonsteroidal MRAs in resistant hypertension specifically within CKD populations remains limited and largely derived from subgroup analyses or extrapolation from diabetic kidney disease trials (Sueta et al., 2020; Iatridi et al., 2026). Large-scale randomized controlled trials focused explicitly on resistant hypertension with varying CKD stages are still needed to confirm efficacy and safety.
Hyperkalemia risk, while reduced compared to steroidal MRAs, is not eliminated and requires careful monitoring, especially in advanced CKD (Bakris et al., 2020). Additionally, long-term renal outcomes and mortality benefits remain to be fully established. The cost and accessibility of novel agents may also limit widespread adoption.
Furthermore, the optimal patient selection criteria, dosing strategies, and combination with other antihypertensive agents require further clarification. Real-world data on adherence and adverse event profiles are currently sparse.
How this may change practice
The emergence of nonsteroidal MRAs offers nephrologists a potentially safer and more effective tool to manage resistant hypertension in CKD patients, a group with high cardiovascular and renal risk and limited therapeutic options. Incorporating these agents could improve blood pressure control while mitigating the hyperkalemia and hormonal side effects associated with traditional MRAs.
Clinicians should consider these novel MRAs in patients with resistant hypertension who have CKD stages 3-4, particularly when standard therapies are insufficient or poorly tolerated. Close monitoring of serum potassium and renal function remains essential. Integration into treatment algorithms may evolve as further evidence accrues.
Ultimately, these agents may complement existing therapies such as renin-angiotensin system blockers and sodium-glucose cotransporter 2 inhibitors, contributing to a more comprehensive and individualized approach to resistant hypertension in CKD.