When should Kerendia (finerenone) be added to the treatment regimen of a patient with chronic kidney disease (CKD) and type 2 diabetes who is already receiving renin-angiotensin-aldosterone system (RAAS) inhibitors, such as Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs)?

When to Add Kerendia (Finerenone)

Add finerenone to the treatment regimen of patients with type 2 diabetes and CKD who have persistent albuminuria (any level) despite maximally tolerated ACE inhibitor or ARB therapy, provided eGFR ≥25 ml/min/1.73 m² and serum potassium ≤5.0 mmol/L. 1

Patient Selection Criteria

Required Baseline Characteristics

• Type 2 diabetes with CKD (eGFR 25-90 ml/min/1.73 m²) 1
• Persistent albuminuria at any level despite current standard of care treatment with glucose-lowering and antihypertensive medications 1
• Already receiving maximally tolerated ACE inhibitor or ARB as foundational therapy 1
• Serum potassium ≤4.8 mmol/L (per trial eligibility) or ≤5.0 mmol/L (per FDA label) 1

Optimal Timing in Treatment Algorithm

• After establishing ACE inhibitor or ARB therapy at the highest tolerated dose 1
• After initiating SGLT2 inhibitor therapy (eGFR ≥20 ml/min/1.73 m²), as SGLT2 inhibitors are the first-line add-on therapy with 1A recommendation 1
• When albuminuria persists despite these foundational therapies, indicating residual cardiorenal risk 1

Dosing Strategy

Initial Dose Selection

• Start with 20 mg daily if eGFR >60 ml/min/1.73 m² 1
• Start with 10 mg daily if eGFR 25-60 ml/min/1.73 m² 1
• Uptitrate to 20 mg daily if tolerated and potassium remains controlled 1

Monitoring Requirements

• Check serum potassium 4 weeks after initiation or dose change 1
• Monitor potassium regularly during treatment to detect hyperkalemia early 1, 2
• Continue monitoring eGFR and albuminuria to assess treatment response 3

Evidence Supporting Addition

Cardiovascular and Renal Benefits

• Finerenone reduces cardiovascular events with hazard ratio 0.86 (95% CI 0.78-0.95; P=0.0018) in the combined FIDELITY analysis 2
• Finerenone reduces renal outcomes with hazard ratio 0.77 (95% CI 0.67-0.88; P=0.0002) for progression to end-stage CKD 2
• All renal events occur less frequently with finerenone than placebo, including progression to end-stage CKD independently of baseline eGFR and albuminuria 2

Additive Effects with SGLT2 Inhibitors

• Combination therapy with finerenone plus empagliflozin produces 29% greater reduction in albuminuria than finerenone alone and 32% greater than empagliflozin alone at 180 days 4
• The combination is safe without unexpected adverse events when initiated simultaneously 4
• Benefits are independent of associated medications including SGLT2 inhibitors 2

Critical Safety Considerations

Hyperkalemia Management

• Hyperkalemia is the primary safety concern but occurs less frequently than with spironolactone 2
• Manage hyperkalemia proactively through dietary potassium restriction, review of concurrent medications, and correction of volume depletion rather than immediately discontinuing therapy 1
• Drug discontinuation due to hyperkalemia is uncommon in clinical trials 4

Contraindications and Precautions

• Do not combine with other mineralocorticoid receptor antagonists (e.g., spironolactone) 1
• Avoid if eGFR <25 ml/min/1.73 m² as this was the trial exclusion criterion 1
• Monitor for symptomatic hypotension especially when combined with multiple antihypertensive agents 4
• Acute kidney injury leading to discontinuation is uncommon but requires monitoring 4

Common Clinical Pitfalls

Do Not Delay Finerenone Because:

• Waiting for "optimal" RAAS blockade - finerenone should be added once maximally tolerated ACE inhibitor/ARB dose is achieved, not delayed indefinitely 1
• Concern about adding another medication - the residual risk reduction justifies combination therapy when albuminuria persists 2
• Mild hyperkalemia concerns - potassium 5.0-5.5 mmol/L can often be managed without stopping therapy 1

Ensure Foundational Therapies First:

• ACE inhibitor or ARB must be established first as finerenone is indicated "in combination with" RAAS blockade 2, 3
• SGLT2 inhibitor should be prioritized as the first add-on therapy given its 1A recommendation strength 1
• Blood pressure control should be optimized to target <130/80 mmHg before adding finerenone 5

Integration with Comprehensive CKD Management

Finerenone Fits Within Multi-Drug Strategy

• Layer 1: ACE inhibitor or ARB for RAAS blockade 1
• Layer 2: SGLT2 inhibitor for kidney and cardiovascular protection 1
• Layer 3: Finerenone for residual albuminuria and additional cardiorenal risk reduction 1
• Layer 4: GLP-1 receptor agonist if additional glucose lowering needed with cardiovascular benefits 6

Monitoring Treatment Response

• Assess albuminuria reduction as the primary marker of finerenone efficacy 4, 2
• Expect gradual eGFR decline slowing rather than immediate improvement 2, 3
• Continue therapy even if eGFR declines unless acute kidney injury or intolerable hyperkalemia develops 7