What are the potential side effects of finerenone (mineralocorticoid receptor antagonist) in patients with chronic kidney disease (CKD) or heart failure?

Side Effects of Finerenone

The primary side effect of finerenone is hyperkalemia, occurring in 10.8-14% of patients compared to 5.3-6.9% with placebo, though severe hyperkalemia requiring permanent discontinuation is rare at only 1.2-1.7% of patients. 1, 2, 3

Hyperkalemia: The Dominant Safety Concern

Hyperkalemia is the most clinically significant adverse effect requiring vigilant monitoring throughout finerenone therapy. 1, 2

Incidence and Severity

• Hyperkalemia occurs in approximately 10.8-14% of finerenone-treated patients versus 5.3-6.9% with placebo in the landmark FIDELIO-DKD and FIGARO-DKD trials 1, 2, 3
• Permanent discontinuation due to hyperkalemia is uncommon, occurring in only 1.2-1.7% of patients on finerenone versus 0.6% on placebo 2, 4
• No deaths from hyperkalemia were reported over 3 years of follow-up in pooled trial data 2
• In real-world settings, only 3.2% of patients experienced unplanned hospitalization with concurrent hyperkalemia up to 6.0 mmol/L 5

Risk Factors for Hyperkalemia

• Lower eGFR, particularly <45 mL/min/1.73 m², increases hyperkalemia risk 2
• Concurrent beta-blocker use elevates hyperkalemia risk 2
• SGLT2 inhibitor co-administration is protective, reducing hyperkalemia risk 2

Management Algorithm for Hyperkalemia

Potassium monitoring schedule: 2, 4

• Check at baseline (must be ≤4.8 mmol/L before initiation)
• Recheck at 1 month after starting finerenone
• Monitor every 4 months during maintenance therapy

Action thresholds based on potassium levels: 2, 4

• ≤4.8 mmol/L: Continue current dose (10 mg or 20 mg daily); proceed with routine monitoring every 4 months
• 4.9-5.5 mmol/L: Continue finerenone at current dose without adjustment; maintain monitoring every 4 months
• >5.5 mmol/L: Immediately hold finerenone, evaluate and adjust dietary potassium intake, review concomitant medications contributing to hyperkalemia, recheck potassium to confirm downtrend, and restart at 10 mg daily when potassium returns to ≤5.0 mmol/L

Renal Function Changes

A transient, modest decline in eGFR occurs early in treatment but stabilizes thereafter. 5

• eGFR decreases slightly from baseline (median 52 mL/min/1.73 m²) to 4 weeks (median 48 mL/min/1.73 m²), representing approximately a 7-8% decline 5
• This initial eGFR decline stabilizes after 4 weeks and does not progress further 5
• This pattern mirrors the hemodynamic changes seen with other cardiorenal protective agents and does not indicate kidney injury 5

Metabolic and Hormonal Effects

Finerenone has a favorable metabolic profile with minimal off-target effects. 6

• No effect on HbA1c or glycemic control 6
• No effect on body weight 6
• No sexual side effects, including gynecomastia, distinguishing it from steroidal mineralocorticoid receptor antagonists like spironolactone 6

Blood Pressure Effects

Finerenone has only a modest effect on blood pressure reduction. 6

• The blood pressure-lowering effect is minimal and not clinically significant in most patients 6
• This distinguishes finerenone from steroidal MRAs, which have more pronounced antihypertensive effects 6

Cardiovascular Safety Profile

Finerenone demonstrates excellent cardiovascular safety with no increase in adverse cardiovascular events. 1, 7

• Treatment-emergent adverse events are balanced between finerenone and placebo groups 7
• Finerenone actually reduces cardiovascular events, including a 13-14% reduction in composite cardiovascular outcomes and a 29% reduction in heart failure hospitalizations 1, 3, 7

Common Pitfalls to Avoid

Do not permanently discontinue finerenone for a single episode of potassium >5.5 mmol/L unless other interventions fail; temporary interruption with dose reduction upon restart (10 mg daily) successfully manages most cases 2

Be aware that potassium measurements have inherent variability due to diurnal and seasonal variation, plasma versus serum sampling differences, and medication effects; consider repeating borderline values before making treatment decisions 2

Do not initiate finerenone in patients with baseline potassium >4.8 mmol/L due to excessive hyperkalemia risk 1, 4

Real-World Safety Experience

In real-world clinical practice, finerenone is safe and well-tolerated with a safety profile consistent with clinical trial data 5

• Most patients (93.5%) in real-world cohorts are successfully treated with concurrent SGLT2 inhibitors, which may provide additional protection against hyperkalemia 5
• Potassium levels increase modestly from baseline (median 4.2 mmol/L) to 4 weeks (median 4.4 mmol/L) but remain stable thereafter 5