What is the role of Finerenone (Finerenone) in managing a patient with chronic kidney disease (CKD), particularly those with diabetic kidney disease?

Finerenone in Chronic Kidney Disease Management

Finerenone should be added as risk-based therapy for patients with type 2 diabetes and chronic kidney disease who have persistent albuminuria (ACR ≥30 mg/g) despite maximum tolerated RAS inhibitor therapy, eGFR ≥25 mL/min/1.73 m², and serum potassium ≤4.8 mmol/L, as it reduces both cardiovascular events and kidney disease progression. 1

Patient Selection Criteria

Finerenone is specifically indicated for patients meeting ALL of the following criteria:

• Type 2 diabetes with chronic kidney disease (stages 2-4) 1
• eGFR 25-90 mL/min/1.73 m² - do not initiate if eGFR <25 or in end-stage renal disease 2
• Persistent albuminuria (ACR ≥30 mg/g) despite optimal therapy 1
• Already on maximum tolerated dose of RAS inhibitor (ACE inhibitor or ARB) 1
• Serum potassium ≤4.8 mmol/L at baseline 1

The 2022 KDIGO/ADA consensus guidelines position finerenone as "additional risk-based therapy" rather than first-line treatment, emphasizing it should only be considered after optimizing foundational therapies. 1

Treatment Sequencing Algorithm

Step 1: Foundation therapy

• RAS inhibitor at maximum tolerated dose (if hypertension or albuminuria present) 1
• SGLT2 inhibitor (initiate if eGFR ≥20; continue until dialysis) 1
• Metformin (if eGFR ≥30) 1

Step 2: Assess for finerenone eligibility

• Check if ACR remains ≥30 mg/g despite above therapies 1
• Verify serum potassium ≤4.8 mmol/L 1
• Confirm eGFR ≥25 mL/min/1.73 m² 2

Step 3: Add finerenone if criteria met

• KDIGO identifies finerenone as "the only nonsteroidal mineralocorticoid receptor antagonist with proven clinical kidney and cardiovascular benefits" 1

This sequencing is critical because SGLT2 inhibitors have larger absolute effects on kidney and cardiovascular outcomes, making them the priority add-on therapy. 2 Finerenone provides complementary benefits through different mechanisms (reducing inflammation and fibrosis). 3

Dosing Protocol

Initial dosing based on eGFR: 2, 4

• eGFR 25-60 mL/min/1.73 m²: Start 10 mg once daily
• eGFR >60 mL/min/1.73 m²: Start 20 mg once daily

Dose uptitration after 1 month: 2

• If serum potassium remains ≤4.8 mmol/L and eGFR is stable, uptitrate from 10 mg to 20 mg daily

No dosing recommendations exist for eGFR <25 mL/min/1.73 m², as the landmark trials (FIDELIO-DKD and FIGARO-DKD) excluded these patients. 2

Clinical Benefits: Cardiovascular and Renal Outcomes

The evidence base comes from two large trials and their pooled analysis (FIDELITY):

Cardiovascular benefits: 1

• 14% reduction in composite cardiovascular outcomes (cardiovascular death, nonfatal MI, nonfatal stroke, heart failure hospitalization): HR 0.86 (95% CI 0.78-0.95)
• 29% reduction in heart failure hospitalization: HR 0.71 (95% CI 0.56-0.90) 5, 6
• Particularly effective at preventing progression from asymptomatic to symptomatic heart failure 4

Kidney benefits: 1

• 18% reduction in composite kidney outcome (kidney failure, sustained ≥40% eGFR decrease, or kidney death): HR 0.82 (95% CI 0.73-0.93)
• 36% reduction in end-stage kidney disease: HR 0.64 (95% CI 0.41-0.995) 4, 5
• 23% reduction in sustained ≥57% eGFR decrease or renal death 5

These benefits were consistent across the spectrum of baseline kidney function (eGFR 25-90 mL/min/1.73 m²) and regardless of concomitant SGLT2 inhibitor use. 5, 7

Hyperkalemia Management: The Primary Safety Concern

Hyperkalemia incidence: 1

• Occurs in 14% with finerenone vs 6.9% with placebo
• Permanent discontinuation due to hyperkalemia: 1.7% vs 0.6%
• No deaths attributed to hyperkalemia over 3 years of follow-up

Monitoring protocol: 2, 4

• Before initiation: Verify potassium ≤4.8 mmol/L
• At 4 weeks: Check potassium and eGFR
• Ongoing: Regular monitoring throughout treatment

Management algorithm for elevated potassium: 2, 5

• Potassium ≤5.5 mmol/L: Continue finerenone
• Potassium >5.5 mmol/L: Withhold finerenone temporarily
• When potassium returns to ≤5.0 mmol/L: Restart at 10 mg daily

A real-world study found that eGFR decreases slightly in the first 4 weeks (from 52 to 48 mL/min/1.73 m²) but stabilizes thereafter, and potassium increases modestly (from 4.2 to 4.4 mmol/L) but remains manageable. 8

Common Pitfalls and Contraindications

Do NOT initiate finerenone if: 2

• eGFR <25 mL/min/1.73 m² or patient is on dialysis
• Baseline potassium >4.8 mmol/L
• Patient not yet optimized on maximum tolerated RAS inhibitor
• Symptomatic heart failure with reduced ejection fraction (these patients were excluded from trials) 5

Critical caveat: While finerenone can be used alongside SGLT2 inhibitors with potentially additive benefits 4, 5, there is "lack of definitive data on benefits and risks when an ns-MRA is added to an SGLT2i." 1 The trials were conducted before SGLT2 inhibitors became standard of care, so real-world combination data is still emerging.

Nephrology referral threshold: Consider referral when eGFR falls below 30 mL/min/1.73 m² for discussion of renal replacement therapy planning. 2, 5

Integration with Heart Failure Management

Finerenone has particular value in patients with diabetic kidney disease who also have heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF), a common comorbidity found in 71% of DKD patients in one real-world study. 8

In these patients, finerenone treatment over 6 months showed: 8

• Reduction in left atrial volume index (from 31.2 to 26.6 mL/m²)
• Improvement in E/e' ratio (from 11.9 to 9.9), indicating better diastolic function
• Stable NT-proBNP levels

The FIGARO-DKD trial specifically demonstrated a 32% reduction in new-onset heart failure among patients without baseline HF history (HR 0.68,95% CI 0.50-0.93). 6

Practical Implementation

Finerenone is most appropriate for:

• Patients with persistent albuminuria despite SGLT2 inhibitor and maximum RAS blockade 2
• Those with SGLT2 inhibitor intolerance or contraindications 2
• Patients at high cardiovascular risk, particularly those prone to heart failure 4, 5

Finerenone provides no benefit for:

• Glucose control (no effect on HbA1c) 9
• Weight management 9
• Blood pressure (only modest effect) 9

The drug's value lies specifically in its anti-inflammatory and anti-fibrotic effects that complement the hemodynamic benefits of SGLT2 inhibitors and RAS inhibitors. 3