Guideline for Mineralocorticoid Receptor Antagonist Use in CKD Patients
For adults with type 2 diabetes, CKD, eGFR >25 mL/min/1.73 m², normal potassium, and persistent albuminuria (ACR >30 mg/g) despite maximum tolerated RAS inhibitor therapy, add a nonsteroidal MRA (specifically finerenone) to reduce CKD progression and cardiovascular events. 1
Patient Selection Criteria
Who Should Receive Nonsteroidal MRA
Type 2 diabetes with CKD and all of the following: 1
- eGFR >25 mL/min/1.73 m²
- Normal serum potassium concentration (≤4.8 mmol/L at baseline)
- Albuminuria ACR ≥30 mg/g (≥3 mg/mmol)
- Already on maximum tolerated dose of ACE inhibitor or ARB
High-risk patients with persistent albuminuria despite standard-of-care therapies (RAS inhibitor, SGLT2 inhibitor) are the most appropriate candidates 1
Nonsteroidal MRA can be added on top of both RAS inhibitor AND SGLT2 inhibitor in adults with type 2 diabetes and CKD 1
Evidence Base for Nonsteroidal MRA
Finerenone is currently the only nonsteroidal MRA with proven clinical kidney and cardiovascular benefits based on the FIDELIO-DKD and FIGARO-DKD trials 1
In the combined FIDELITY analysis, finerenone reduced: 1
- Cardiovascular composite outcomes (HR 0.86; 95% CI 0.78-0.95)
- Kidney composite outcomes including kidney failure (HR 0.77; 95% CI 0.67-0.88)
- Kidney failure requiring dialysis or transplant (HR 0.80; 95% CI 0.64-0.99)
Dosing and Initiation Protocol
Starting Dose Based on eGFR 1
- eGFR 25-59 mL/min/1.73 m²: Start finerenone 10 mg daily
- eGFR ≥60 mL/min/1.73 m²: Start finerenone 20 mg daily
Potassium Monitoring Algorithm 1
At 1 month after initiation, then every 4 months:
K+ ≤4.8 mmol/L:
- Continue current dose
- If on 10 mg daily, increase to 20 mg daily
- Monitor K+ every 4 months
K+ 4.9-5.5 mmol/L:
- Continue current dose (10 mg or 20 mg)
- Monitor K+ every 4 months
K+ >5.5 mmol/L:
- Hold finerenone immediately
- Adjust diet or concomitant medications to reduce potassium
- Recheck potassium
- Restart 10 mg daily when K+ ≤5.0 mmol/L
Key Safety Considerations
Select patients with consistently normal serum potassium before initiation to mitigate hyperkalemia risk 1
Hyperkalemia incidence: 14% with finerenone vs 6.9% with placebo over 3 years, but permanent discontinuation for hyperkalemia was only 1.7% vs 0.6%, with no deaths from hyperkalemia 1
Check potassium within 2-4 weeks of initiation or dose change, then at 1 month, then every 4 months 1
Steroidal MRA Use in CKD
Limited Indications 1
Steroidal MRA (spironolactone, eplerenone) may be used for:
- Heart failure treatment
- Hyperaldosteronism
- Resistant hypertension (if eGFR ≥45 mL/min/1.73 m²)
Steroidal MRA cause higher rates of hyperkalemia and reversible GFR decline, particularly in patients with low baseline GFR 1
Current guidelines recommend against steroidal MRA in advanced CKD due to safety concerns 2, 3
Integration with Other CKD Therapies
Treatment Hierarchy for Type 2 Diabetes and CKD 1
First-line therapy:
- SGLT2 inhibitor (initiate if eGFR ≥20 mL/min/1.73 m²)
- RAS inhibitor at maximum tolerated dose (if hypertension present)
- Metformin (if eGFR ≥30 mL/min/1.73 m²)
Additional risk-based therapy:
- Nonsteroidal MRA if ACR ≥30 mg/g and normal potassium 1
- GLP-1 RA if needed for glycemic targets
- Additional antihypertensives as needed
Common Pitfalls to Avoid
Do not use steroidal MRA as first choice when nonsteroidal MRA with proven benefits (finerenone) is available for diabetic CKD 1
Do not withhold nonsteroidal MRA due to fear of hyperkalemia in appropriately selected patients with normal baseline potassium—the absolute risk of treatment discontinuation is low (1.7%) 1
Do not use MRA in patients with baseline hyperkalemia or eGFR ≤25 mL/min/1.73 m² 1
Prioritize agents with documented kidney or cardiovascular benefits (currently finerenone only) rather than other nonsteroidal MRA without established long-term outcomes 1
Do not combine steroidal and nonsteroidal MRA—choose one based on indication and safety profile 1