What are the benefits and risks of using spironolactone (aldosterone antagonist) in patients with Impaired renal function (IRF) on dialysis, as investigated in the recent Spiro trial?

Spironolactone in Dialysis Patients: Benefits and Risks

Spironolactone should be used with extreme caution in dialysis patients due to high risks of hyperkalemia, with careful monitoring of potassium levels and consideration of lower dosing, despite potential cardiovascular benefits.

Benefits of Spironolactone in Dialysis Patients

Spironolactone, an aldosterone receptor antagonist, has shown several potential benefits in patients with heart failure:

• Reduces mortality by 30% in patients with severe heart failure (NYHA class III-IV) 1
• Decreases hospitalizations for worsening heart failure by 35% 1
• Improves NYHA functional class in heart failure patients 1
• May reduce sudden cardiac death by 30-54% in heart failure patients 2
• Potentially reduces left ventricular hypertrophy and improves diastolic function 2

Risks in Dialysis Patients

However, in patients with impaired renal function on dialysis, spironolactone presents significant risks:

• Hyperkalemia: The primary concern, especially in advanced kidney disease
• Increased mortality: Higher all-cause mortality (adjusted HR 1.35) in pre-dialysis stage 5 CKD patients 3
• Infection-related death: Higher risk (adjusted HR 1.42) in advanced CKD 3
• Heart failure hospitalization: Increased risk (adjusted HR 1.35) in pre-dialysis stage 5 CKD 3

Current Guideline Recommendations

Guidelines are cautious about spironolactone use in dialysis patients:

• Contraindicated in advanced kidney disease (eGFR <30 mL/min/1.73m²) due to life-threatening hyperkalemia risk 1
• The 2022 AHA/ACC/HFSA heart failure guideline acknowledges that spironolactone and beta blockers might be protective in patients with heart failure and worsening renal function, but does not specifically endorse use in dialysis patients 2
• KDIGO notes that some trials in dialysis patients have shown cardiovascular benefits with spironolactone while others have not 2

Evidence from Recent Research

Small studies have shown mixed results:

• Some small prospective trials suggest spironolactone might not increase hyperkalemia rates in carefully selected hemodialysis patients 4
• However, a nationwide population-based study found increased risks of all-cause mortality, infection-related death, and heart failure hospitalization in pre-dialysis stage 5 CKD patients 3
• The ACHIEVE trial was designed to determine if spironolactone 25 mg daily prevents cardiovascular mortality and heart failure hospitalizations in dialysis patients, but was stopped early due to futility 5

Monitoring Protocol if Used

If spironolactone is prescribed in dialysis patients:

• Baseline assessment: Serum potassium must be <5.0 mEq/L before initiation 1
• Dosing: Consider lower doses (12.5-25 mg) or alternate-day dosing 1
• Monitoring schedule: Check potassium and renal function at baseline, 1 week, 1 month, and then at 1,2,3, and 6 months after initiation 1
• Discontinuation criteria: Consider discontinuation if potassium >5.5 mEq/L or if creatinine >2.5 mg/dL (221 μmol/L) 1

Risk Factors for Adverse Events

Patients at highest risk for complications:

• Elderly patients 1
• Those with baseline potassium >4.5 mmol/L 1
• Patients on concomitant medications that increase potassium (ACE inhibitors, ARBs, NSAIDs) 1
• Avoid triple therapy with ACE inhibitors and ARBs due to extreme hyperkalemia risk 1

Conclusion

While spironolactone has proven cardiovascular benefits in heart failure patients with normal or mildly impaired renal function, its use in dialysis patients remains controversial. The risk of hyperkalemia and increased mortality in advanced CKD patients suggests that extreme caution should be exercised. If prescribed, close monitoring of potassium levels is essential, and lower doses should be considered. The ongoing ACHIEVE trial may provide more definitive evidence on the efficacy and safety of spironolactone in this population.