In a patient with congestive heart failure and severe renal impairment, would you add a SGLT2 inhibitor or a MRA (mineralocorticoid receptor antagonist) first?

SGLT2 Inhibitor Should Be Added First

In a patient with CHF, severe renal impairment (CrCl 19 mL/min), controlled blood pressure, and normal potassium, add an SGLT2 inhibitor first before considering an MRA. 1

Rationale for SGLT2 Inhibitor Priority

Safety Profile in Severe CKD

• SGLT2 inhibitors can be safely initiated at eGFR ≥20 mL/min/1.73 m² and continued even if eGFR falls below this threshold once started. 1
• These agents have minimal impact on blood pressure and renal hemodynamics, making them the safest initial choice in patients with borderline renal function. 2
• SGLT2 inhibitors reduce the risk of serious hyperkalemia (HR 0.84; 95% CI 0.76-0.93), which is particularly important when planning to add additional GDMT. 1

Cardiovascular and Renal Benefits

• SGLT2 inhibitors reduce heart failure hospitalizations and cardiovascular mortality in HFrEF patients. 1, 2
• They provide kidney protection and should be continued until dialysis or transplant. 1
• A reversible decrease in eGFR with SGLT2 inhibitor initiation may occur and is generally not an indication to discontinue therapy. 1

Facilitates Future GDMT Optimization

• Starting an SGLT2 inhibitor first creates an opportunity for simultaneous introduction or reintroduction of other GDMT components, including MRAs, by reducing hyperkalemia risk. 1
• This strategy allows for more aggressive GDMT optimization without the limiting adverse effect of hyperkalemia. 1

Why Not MRA First

Renal Function Constraints

• Your patient's CrCl of 19 mL/min is below the recommended threshold for MRA initiation. 1
• Guidelines recommend MRAs only when eGFR is ≥30 mL/min/1.73 m² for steroidal MRAs (spironolactone/eplerenone). 1
• Nonsteroidal MRAs require eGFR ≥25 mL/min/1.73 m², which your patient also does not meet. 1

Hyperkalemia Risk

• MRAs cause hyperkalemia and reversible decline in glomerular filtration, particularly in patients with low GFR. 1
• While the patient's current potassium is 4.2 mEq/L, the risk of developing severe hyperkalemia increases substantially with MRA use at this level of renal function. 1
• Major MRA trials (RALES, EPHESUS, EMPHASIS-HF) excluded patients with serum creatinine >2.5 mg/dL or eGFR <30 mL/min. 1

Blood Pressure Considerations

• The patient's BP of 156/71 mmHg suggests adequate blood pressure for SGLT2 inhibitor initiation without significant hypotension risk. 2
• MRAs may require more aggressive blood pressure management in combination with other GDMT. 3

Practical Implementation Strategy

SGLT2 Inhibitor Initiation

• Choose an agent with documented kidney and cardiovascular benefits (dapagliflozin, empagliflozin, or canagliflozin). 1
• Consider reducing loop diuretic dose if patient is at risk for hypovolemia before starting SGLT2 inhibitor. 1
• Monitor for volume depletion symptoms and follow up on volume status after drug initiation. 1
• Recheck renal function and electrolytes in 1-2 weeks after initiation. 3

Future MRA Consideration

• Reassess for MRA addition only after SGLT2 inhibitor is established and if renal function stabilizes or improves to eGFR ≥25-30 mL/min/1.73 m². 1
• If considering nonsteroidal MRA (finerenone), ensure eGFR ≥25 mL/min/1.73 m² and potassium remains normal. 1
• Monitor potassium closely (at 1 week, 4 weeks, then regularly) if MRA is eventually added. 4

Critical Pitfalls to Avoid

• Do not withhold SGLT2 inhibitors due to concerns about the low eGFR—they are indicated down to eGFR 20 mL/min/1.73 m². 1, 2
• Do not start MRA at this level of renal function (CrCl 19) as it violates guideline recommendations and significantly increases hyperkalemia risk. 1
• Do not interpret a modest eGFR decline after SGLT2 inhibitor initiation as treatment failure—this is expected and acceptable. 1, 3
• Avoid triple RAS blockade (ACEi + ARB + MRA) due to increased risk of renal dysfunction and hyperkalemia. 2