Would spironolactone be an appropriate choice for additional diuresis in a patient with CHF with reduced ejection fraction on Entresto (sacubitril/valsartan), dapagliflozin, and Lasix (furosemide) with CKD stage IV and fluid overload?

Spironolactone Use in HFrEF with CKD Stage IV and Fluid Overload

Spironolactone should NOT be initiated in this patient with CKD stage IV (eGFR 15-29 mL/min/1.73 m²) due to high risk of life-threatening hyperkalemia, and alternative diuretic strategies should be pursued instead.

Primary Contraindication Based on Renal Function

The FDA label for spironolactone explicitly excludes patients with baseline serum creatinine >2.5 mg/dL from the landmark RALES trial, which demonstrated mortality benefit in heart failure 1. CKD stage IV typically corresponds to creatinine levels well above this threshold, placing your patient outside evidence-based safety parameters.

Key exclusion criteria from pivotal trials:

• Baseline creatinine >2.5 mg/dL 1
• Baseline potassium >5.0 mEq/L 1
• These restrictions exist because serious hyperkalemia risk increases exponentially with declining renal function

Guideline-Based Recommendations for Advanced CKD

The 2016 ESC guidelines specify that spironolactone should be used at low doses (12.5-25 mg daily initially, target 50 mg) in NYHA class III-IV patients 2. However, older ESC guidelines from 2002 recommend spironolactone specifically for patients in NYHA class III who improved from class IV or are currently class IV, with doses ≤12.5-50 mg daily 2. Critically, these recommendations assume adequate renal function and do not address CKD stage IV.

The 2001 ESC guidelines explicitly state that potassium-sparing diuretics including spironolactone should only be used with "frequent measurement of creatinine and electrolytes" and recommend checking these values every 5-7 days after initiation until stable 2. In CKD stage IV, this monitoring burden becomes impractical and dangerous.

Alternative Diuretic Strategies for Your Patient

For additional diuresis in this clinical scenario, consider:

• Increase loop diuretic (furosemide) dose: The 2016 ESC guidelines recommend titrating loop diuretics to achieve euvolemia, with usual daily doses of 40-240 mg for furosemide 2. Your patient likely needs dose escalation before adding other agents.

• Add thiazide-type diuretic synergistically: The 2002 ESC guidelines recommend combining loop diuretics with thiazides (such as metolazone) for resistant edema, though this requires "frequent measurement of creatinine and electrolytes" 2. The 2016 ESC guidelines note thiazides should not be used if eGFR <30 mL/min/1.73 m² except when prescribed synergistically with loop diuretics 2. This combination can be highly effective but requires intensive monitoring.

• Optimize existing GDMT: Ensure Entresto and dapagliflozin are at target doses, as both provide additional diuretic effects and improve outcomes even in advanced CKD 3, 4.

Evidence Regarding Spironolactone Safety in Advanced CKD

Recent observational data suggests spironolactone may be used cautiously in selected CKD patients, but the evidence is limited and conflicting:

• A 2021 retrospective study found only 6.6% of hospitalized HF patients with CKD stages 3-5 experienced hyperkalemia with spironolactone, though notably all hyperkalemia cases occurred in patients on spironolactone prior to admission (not newly initiated) 5

• A 2015 review acknowledged that "most supporting trials have excluded patients with renal dysfunction resulting in a dearth of data to support use of spironolactone in CKD patients with CHF" 6

• The TOPCAT trial in HFpEF showed spironolactone increased worsening renal function (17.8% vs 11.6% with placebo), though this was in a population with better baseline renal function than your patient 7

Critical Pitfalls to Avoid

The combination of Entresto (which contains valsartan, an ARB) plus spironolactone in the setting of CKD stage IV creates extreme hyperkalemia risk. The 2016 ESC guidelines explicitly warn against combining ACE inhibitor with ARB and MRA due to "increased risk of renal dysfunction and life-threatening hyperkalemia" 2. While Entresto is an ARNI (not a pure ARB), it still blocks the angiotensin II receptor and carries similar risks.

The 2001 ESC guidelines state that "until recently the combination of potassium sparing diuretics and ACE inhibitors was regarded as potentially dangerous" and recommend this combination only for persistent diuretic-induced hypokalemia despite ACE inhibitor therapy 2. Your patient is on RAAS blockade (Entresto) and has advanced CKD—the opposite clinical scenario.

Practical Algorithm for This Patient

1. Maximize loop diuretic dose (furosemide up to 240 mg daily or higher if needed) 2
2. If inadequate response, add metolazone 2.5-5 mg daily with intensive monitoring (daily weights, electrolytes every 2-3 days initially) 2
3. Ensure Entresto and dapagliflozin are at target doses (97/103 mg BID and 10 mg daily respectively) 2, 4
4. Consider ultrafiltration or dialysis consultation if refractory to medical management given CKD stage IV 2
5. Avoid spironolactone unless under nephrology co-management with very close monitoring (potassium checks every 3-5 days) and only if absolutely no other options exist 2, 6

If spironolactone were to be considered despite these concerns, start at 12.5 mg every other day (not daily) with potassium and creatinine checks every 5-7 days 2. However, given the patient's advanced CKD stage IV, this approach carries unacceptable risk in routine clinical practice.