What is the role of Kerendia (finerenone) in managing chronic kidney disease (CKD) associated with type 2 diabetes?

Role of Kerendia (Finerenone) in Managing CKD Associated with Type 2 Diabetes

Finerenone (Kerendia) is strongly recommended for patients with type 2 diabetes and chronic kidney disease with albuminuria, as it significantly reduces both kidney disease progression and cardiovascular events across a broad spectrum of CKD severity. 1

Efficacy in Renal Outcomes

• Finerenone demonstrated an 18% reduction in the primary kidney composite endpoint (kidney failure, sustained decrease in eGFR >40% from baseline, or renal death) in the FIDELIO-DKD trial (HR 0.82 [95% CI 0.73-0.93]; P = 0.001) 1
• In the pooled FIDELITY analysis, finerenone reduced the risk of the composite kidney outcome by 23% compared to placebo (HR 0.77 [95% CI 0.67-0.88]; P = 0.0002) 1, 2
• Notably, finerenone reduced end-stage kidney disease by 36% (HR 0.64 [95% CI 0.41-0.995]), a clinically significant outcome for patients 1
• The renal benefits were consistent across different baseline kidney function levels (eGFR 25-90 mL/min/1.73 m²) 3

Cardiovascular Benefits

• Finerenone reduced the key secondary cardiovascular composite outcome by 14% in the FIDELIO-DKD trial (HR 0.86 [95% CI 0.75-0.99]; P = 0.03) 1
• In the FIGARO-DKD trial, which focused on cardiovascular outcomes, finerenone reduced the primary cardiovascular composite endpoint by 13% (HR 0.87 [95% CI 0.76-0.98]; P = 0.03) 1
• The cardiovascular benefit was primarily driven by a 29% reduction in heart failure hospitalizations (HR 0.71 [95% CI 0.56-0.90]) 1, 3
• The FIDELITY pooled analysis showed a 14% reduction in composite cardiovascular outcomes (HR 0.86 [95% CI 0.78-0.95]; P = 0.0018) 1, 2

Mortality Benefits

• Finerenone significantly reduced all-cause mortality (HR 0.82 [95% CI 0.70-0.96]; P = 0.014) and cardiovascular mortality (HR 0.82 [95% CI 0.67-0.99]; P = 0.040) in on-treatment analyses 4
• Notably, finerenone lowered the incidence of sudden cardiac death compared to placebo (HR 0.75 [95% CI 0.57-0.996]; P = 0.046) 4

Mechanism of Action and Albuminuria Reduction

• As a non-steroidal mineralocorticoid receptor antagonist (MRA), finerenone works differently from traditional MRAs like spironolactone 1
• Early albuminuria reduction with finerenone mediates 84% of the treatment effect on kidney outcomes and 37% of the effect on cardiovascular outcomes 5
• A 30% or greater reduction in UACR was achieved in 53.2% of patients receiving finerenone compared to 27.0% with placebo 5

Patient Selection and Dosing

• Finerenone is indicated for adults with chronic kidney disease associated with type 2 diabetes 6
• For patients with eGFR 25-60 mL/min/1.73 m², the recommended starting dose is 10 mg once daily 1, 3
• For patients with eGFR >60 mL/min/1.73 m², the recommended starting dose is 20 mg once daily 1, 3
• Dose increase from 10 mg to 20 mg once daily should be considered after 1 month if serum potassium is ≤4.8 mmol/L and eGFR is stable 1

Safety Considerations and Monitoring

• The most common adverse effect is hyperkalemia, which occurred in 14% of finerenone patients versus 6.9% with placebo 1
• Permanent discontinuation due to hyperkalemia was relatively low (1.7% with finerenone vs. 0.6% with placebo) 1, 2
• No deaths related to hyperkalemia were reported in the clinical trials 1
• Serum potassium should be ≤4.8 mmol/L before initiating therapy 1
• Regular monitoring of serum potassium is essential, particularly when initiating therapy 7

Combination with Other Therapies

• Finerenone can be used alongside SGLT2 inhibitors for complementary cardiorenal protection 3, 7
• In the FIDELIO-DKD trial, only 4.5% of participants were on SGLT2 inhibitors, so more data on combination therapy is needed 1
• Patients should already be on a maximum tolerated dose of a renin-angiotensin system inhibitor (ACE inhibitor or ARB) before adding finerenone 1, 7
• Avoid triple therapy with ACE inhibitors and ARBs together with finerenone due to increased risk of adverse events 7

Clinical Algorithm for Use

1. Patient identification: Select patients with type 2 diabetes and CKD with albuminuria (UACR ≥30 mg/g) and eGFR ≥25 mL/min/1.73 m² 1
2. Baseline assessment: Check serum potassium (must be ≤4.8 mmol/L) and ensure patient is on maximum tolerated dose of ACE inhibitor or ARB 1
3. Dosing: Start with 10 mg daily if eGFR 25-60 mL/min/1.73 m² or 20 mg daily if eGFR >60 mL/min/1.73 m² 1, 3
4. Monitoring: Check potassium levels 4 weeks after initiation and with any dose adjustment 7
5. Dose adjustment: Consider increasing from 10 mg to 20 mg after 1 month if potassium remains ≤4.8 mmol/L and eGFR is stable 1
6. Consider nephrology referral: When eGFR <30 mL/min/1.73 m² for management of advanced kidney disease 1, 3