Is spironolactone (aldosterone antagonist) still beneficial for a patient with end-stage Chronic Kidney Disease (CKD)?

Spironolactone Use in End-Stage Chronic Kidney Disease

Spironolactone should be avoided in patients with end-stage chronic kidney disease (eGFR <30 mL/min/1.73m²) due to the significantly increased risk of hyperkalemia and potential for cardiac arrest. 1

Risk Assessment in End-Stage CKD

• Spironolactone is substantially excreted by the kidney, and the risk of adverse reactions is greater in patients with impaired renal function 2
• Patients with end-stage CKD are at particularly high risk of developing hyperkalemia with spironolactone, which can lead to life-threatening cardiac arrhythmias 1, 3
• A recent randomized controlled trial (2024) found that spironolactone was frequently discontinued due to safety concerns in CKD patients, with no evidence of cardiovascular benefit in stage 3b CKD 4
• Two-thirds of participants in this trial stopped treatment within 6 months, predominantly due to decreased eGFR (35.4%), treatment side effects (18.9%), and hyperkalemia (8.0%) 4

Guidelines on Spironolactone Use in Advanced CKD

• The American College of Cardiology/American Heart Association guidelines explicitly state that spironolactone should be avoided when serum creatinine is greater than 2.5 mg/dL in men or greater than 2.0 mg/dL in women (or eGFR <30 mL/min/1.73 m²) 5
• Inappropriate use of aldosterone receptor antagonists is potentially harmful because of life-threatening hyperkalemia or renal insufficiency in patients with advanced kidney disease 5
• For patients with heart failure, the guidelines specify that creatinine should be ≤2.5 mg/dL in men or ≤2.0 mg/dL in women (or eGFR >30 mL/min/1.73 m²), and potassium should be <5.0 mEq/L before initiating spironolactone 5

Hyperkalemia Risk in End-Stage CKD

• The risk of hyperkalemia with spironolactone increases progressively as renal function declines 1
• Risk factors that further increase hyperkalemia risk include:
  • Concomitant use of ACE inhibitors or ARBs 1, 3
  • Baseline potassium ≥5.0 mEq/L 1
  • Diabetes mellitus 1
  • Use of NSAIDs or COX-2 inhibitors 1
  • Concurrent use of other potassium-sparing diuretics 1

Evidence on Benefits vs. Risks

• While spironolactone has shown mortality benefits in heart failure patients with preserved renal function 5, these benefits have not been consistently demonstrated in end-stage CKD
• A 2018 study suggested potential benefits in reducing progression to ESRD in stage 3-4 CKD patients, but also showed a significantly higher incidence of hyperkalemia-associated hospitalization (hazard ratio 3.17) 6
• The 2024 randomized controlled trial conclusively showed that spironolactone should not be used for people with stage 3b CKD without another explicit treatment indication, as it provided no cardiovascular benefit while causing significant safety issues 4

Alternative Approaches for End-Stage CKD Patients

• For patients with heart failure and end-stage CKD, alternative pharmacological treatments should be considered 5
• A combination of nitrates and hydralazine has shown favorable effects on survival in patients with mild to moderate heart failure symptoms 5
• For blood pressure control in CKD patients, other antihypertensive medications with better safety profiles in advanced kidney disease should be considered 5

Monitoring Requirements If Used Despite Risks

• If spironolactone must be used in a patient with advanced CKD (which is generally not recommended):
  • Start with very low doses (12.5 mg daily or every other day) 1
  • Monitor potassium and renal function at 3 days and 1 week after initiation, and at least monthly thereafter 1
  • Discontinue immediately if potassium ≥6.0 mEq/L 1
  • Consider hospitalization for initiation to allow for close monitoring 5

In conclusion, the evidence strongly indicates that spironolactone should be avoided in patients with end-stage CKD due to the high risk of hyperkalemia and lack of proven benefit in this population. The potential risks outweigh the potential benefits in this specific patient group.