What is the recommended treatment for a patient with Chronic Kidney Disease (CKD) and persistent albuminuria despite first-line therapy, considering the use of nonsteroidal mineralocorticoid receptor antagonist (ns-MRA)?

Nonsteroidal Mineralocorticoid Receptor Antagonist (ns-MRA) for CKD with Persistent Albuminuria

Add a nonsteroidal MRA (specifically finerenone) to the treatment regimen for adults with type 2 diabetes, CKD with eGFR >25 ml/min per 1.73 m², normal serum potassium (≤4.8 mmol/L), and albuminuria >30 mg/g despite maximum tolerated RAS inhibitor therapy. 1

Patient Selection Criteria

Before initiating ns-MRA therapy, verify the following eligibility requirements:

• Type 2 diabetes with CKD and persistent albuminuria (ACR ≥30 mg/g or ≥3 mg/mmol) despite maximum tolerated dose of ACE inhibitor or ARB 1
• eGFR >25 ml/min per 1.73 m² at initiation 1
• Serum potassium ≤4.8 mmol/L (or ≤5.0 mmol/L per FDA label) with consistently normal levels 1
• High risk for CKD progression and cardiovascular events, demonstrated by persistent albuminuria despite standard-of-care therapies including RAS inhibitors and ideally SGLT2 inhibitors 1

Rationale for ns-MRA Use

The KDIGO 2024 guidelines provide a Grade 2A recommendation for ns-MRA therapy in this clinical scenario, reflecting strong evidence from the FIDELIO-DKD and FIGARO-DKD trials. 1 Finerenone is currently the only ns-MRA with proven kidney and cardiovascular benefits, demonstrating significant reductions in both composite kidney outcomes (kidney failure, sustained ≥40% eGFR decrease, or kidney death; HR 0.82) and cardiovascular outcomes (cardiovascular death, nonfatal MI, nonfatal stroke, or heart failure hospitalization; HR 0.86-0.87). 1

Ns-MRAs can be added on top of both RAS inhibitors and SGLT2 inhibitors, providing complementary mechanisms of renoprotection. 1 The albuminuria reduction achieved with finerenone mediates 84% of the treatment effect on kidney outcomes and 37% of the effect on cardiovascular outcomes. 2

Finerenone Dosing Protocol

Initial Dosing Based on eGFR:

• eGFR ≥60 ml/min per 1.73 m²: Start finerenone 20 mg once daily 1
• eGFR 25-59 ml/min per 1.73 m²: Start finerenone 10 mg once daily 1

Potassium Monitoring and Dose Adjustment Algorithm:

At 1 month after initiation, then every 4 months: 1

Serum Potassium Level	Action
≤4.8 mmol/L	• Continue current dose • If on 10 mg daily, increase to 20 mg daily • Monitor K+ every 4 months [1]
4.9-5.5 mmol/L	• Continue finerenone at current dose (10 or 20 mg) • Monitor K+ every 4 months [1]
>5.5 mmol/L	• Hold finerenone immediately • Adjust diet or concomitant medications to reduce potassium • Recheck K+ levels • Restart at 10 mg daily when K+ ≤5.0 mmol/L [1]

Critical Safety Considerations

Hyperkalemia is the primary adverse event requiring vigilant monitoring. In clinical trials, hyperkalemia occurred in 14% of finerenone-treated patients versus 6.9% with placebo, but permanent discontinuation due to hyperkalemia was only 1.7% versus 0.6%, with no deaths attributed to hyperkalemia over 3 years. 1

Select patients with consistently normal baseline potassium levels to minimize hyperkalemia risk. 1 Avoid initiating ns-MRA in patients with baseline potassium >4.8 mmol/L or those with recurrent hyperkalemia on RAS inhibitors. 1

Continue finerenone even if eGFR falls below 25 ml/min per 1.73 m² during treatment, as long as potassium remains acceptable and the drug is tolerated. 1 This mirrors the approach with SGLT2 inhibitors, where continuation despite declining eGFR maintains benefit. 1

Integration with Other CKD Therapies

The optimal treatment sequence for diabetic CKD now includes layered therapy:

1. First-line foundation: RAS inhibitor (ACE inhibitor or ARB) at maximum tolerated dose 1
2. Add SGLT2 inhibitor for all patients with T2D and eGFR ≥20 ml/min per 1.73 m² 1
3. Add ns-MRA (finerenone) if albuminuria persists (≥30 mg/g) despite RAS inhibitor and ideally SGLT2 inhibitor 1

This triple therapy approach (RAS inhibitor + SGLT2 inhibitor + ns-MRA) is explicitly endorsed by KDIGO guidelines for patients with persistent albuminuria and represents the most comprehensive renoprotective strategy currently available. 1

Common Pitfalls to Avoid

• Do not withhold ns-MRA solely due to declining eGFR if potassium remains controlled and the patient tolerates therapy 1
• Do not combine steroidal MRAs (spironolactone, eplerenone) with ns-MRAs, as this increases hyperkalemia risk without additional benefit 1
• Do not skip the 1-month potassium check after initiation or dose adjustment, as this is the critical window for detecting hyperkalemia 1
• Prioritize finerenone over other ns-MRAs (esaxerenone, apararenone) as it is the only agent with documented kidney and cardiovascular outcome benefits 1