What is Kerendia (finerenone)?

Kerendia (Finerenone): A Selective Non-Steroidal Mineralocorticoid Receptor Antagonist for Cardiorenal Protection

Kerendia (finerenone) is a first-in-class, selective, non-steroidal mineralocorticoid receptor antagonist (MRA) that significantly reduces the risk of kidney failure progression, cardiovascular events, and mortality in adults with chronic kidney disease associated with type 2 diabetes. 1

Mechanism and Classification

Finerenone works by selectively blocking mineralocorticoid receptors, which differentiates it from older steroidal MRAs like spironolactone. This selective action provides:

• More targeted kidney and cardiovascular protection
• Lower risk of endocrine-related side effects compared to steroidal MRAs
• Reduced risk of hyperkalemia compared to traditional MRAs (though still requiring monitoring)

Clinical Evidence and Benefits

Kerendia has demonstrated significant benefits in two major clinical trials:

1. FIDELIO-DKD trial: Showed significant reduction in the primary composite kidney outcome (kidney failure, sustained decrease ≥40% in eGFR, or death from kidney causes) with a hazard ratio of 0.82 2

2. FIGARO-DKD trial: Demonstrated 13% reduction in the primary cardiovascular outcome (cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure) 2

3. FIDELITY pooled analysis: Combined analysis of both trials showed:

   • 14% reduction in cardiovascular outcomes (HR 0.86) 2
   • 23% reduction in kidney outcomes (HR 0.77) 2
   • Consistent benefits across different levels of kidney function and albuminuria 3

Indications and Patient Selection

Kerendia is indicated for adults with:

• Chronic kidney disease associated with type 2 diabetes
• Albuminuria (ACR ≥30 mg/g)
• Currently on maximum tolerated dose of renin-angiotensin system inhibitors (ACE inhibitors or ARBs)

Dosing and Administration

• Initial dosing: Based on baseline eGFR
  • eGFR 25-60 mL/min/1.73m²: 10 mg once daily
  • eGFR ≥60 mL/min/1.73m²: 20 mg once daily
• Dose may be increased from 10 mg to 20 mg once daily after 1 month if serum potassium ≤4.8 mmol/L and eGFR remains stable 2

Monitoring and Safety

• Hyperkalemia: Most common adverse effect, requiring regular monitoring

  • Baseline serum potassium should be <4.8 mmol/L before initiation
  • Monitor potassium levels regularly after starting therapy
  • Discontinuation due to hyperkalemia occurred in 1.7% of patients on finerenone vs 0.6% on placebo 3

• Other safety considerations:

  • Generally well-tolerated with similar overall safety profile to placebo
  • No significant increase in risk of gynecomastia or sexual dysfunction (unlike steroidal MRAs)

Position in Treatment Algorithm

Kerendia should be considered as additional risk-based therapy for patients with:

• Type 2 diabetes and CKD with albuminuria (ACR ≥30 mg/g)
• Normal potassium levels
• Already on maximum tolerated dose of RAS inhibitors 2

In the treatment algorithm, Kerendia fits as:

1. First-line therapies: SGLT2 inhibitor, metformin (if eGFR ≥30), RAS inhibitor, statin
2. Additional risk-based therapy: Finerenone when albuminuria persists despite RAS inhibition 2
3. Other therapies as needed: GLP-1 receptor agonists, antihypertensives, etc.

Clinical Pearls and Pitfalls

• Key advantage: Provides cardiorenal protection beyond what is achieved with RAS inhibitors alone
• Common pitfall: Failing to monitor potassium levels, especially in the first months of treatment
• Important distinction: Unlike SGLT2 inhibitors, Kerendia does not lower blood glucose and is not used for glycemic control
• Synergistic approach: Can be used alongside SGLT2 inhibitors for complementary cardiorenal protection 2
• Patient selection: Ensure normal potassium levels before initiation to minimize hyperkalemia risk

Kerendia represents an important advancement in the management of patients with type 2 diabetes and CKD, offering additional cardiorenal protection when added to standard therapies.