Can spironolactone (aldosterone antagonist) cause Acute Kidney Injury (AKI)?

From the Guidelines

Yes, spironolactone can cause acute kidney injury (AKI). This potassium-sparing diuretic works by blocking aldosterone receptors in the kidneys, which can lead to reduced kidney function in certain circumstances. AKI is more likely to occur when spironolactone is used in patients with pre-existing kidney disease, dehydration, or when combined with other medications that affect kidney function like ACE inhibitors, ARBs, or NSAIDs. The risk increases with higher doses (typically above 25-50mg daily) and in elderly patients. Spironolactone can cause hyperkalemia (high potassium levels), which may contribute to kidney damage. It can also reduce glomerular filtration rate by decreasing blood pressure and renal perfusion, especially in volume-depleted patients.

Key Considerations

• Regular monitoring of kidney function and electrolytes is essential when taking spironolactone, particularly during the first few weeks of treatment and after dose adjustments 1.
• If signs of AKI develop, such as decreased urine output, swelling, or fatigue, the medication may need to be reduced or discontinued 1.
• The development of potassium levels in excess of 5.5 mEq per liter should generally trigger discontinuation or dose reduction of the aldosterone antagonist unless patients have been receiving potassium supplementation, which should then be stopped 1.
• Patients should be cautioned to avoid the addition of nonsteroidal anti-inflammatory agents and cyclo-oxygenase-2 inhibitors, which can lead to worsening renal function and hyperkalemia 1.

Monitoring and Management

• Potassium levels and renal function should be rechecked within 3 days and again at 1 week after initiation of an aldosterone antagonist 1.
• Subsequent monitoring should be dictated by the general clinical stability of renal function and fluid status but should occur at least monthly for the first 3 months and every 3 months thereafter 1.
• The addition or an increase in dosage of ACEIs or ARBs should trigger a new cycle of monitoring 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Spironolactone and Acute Kidney Injury (AKI)

• Spironolactone has been associated with an increased risk of hyperkalemia and AKI in patients with heart failure, particularly when used in combination with loop diuretics 2.
• The incidence rates of hyperkalemia and AKI in patients using spironolactone with a loop diuretic were 2.9 and 10.1 events per 1000 person-months, respectively 2.
• However, other studies suggest that spironolactone may prevent the transition from AKI to chronic kidney disease (CKD) by reducing inflammation and promoting tissue repair 3.
• Spironolactone has also been shown to prevent CKD caused by ischemic AKI in animal models, and may be a promising treatment for the prevention of AKI-induced CKD 4.

Safety and Tolerability of Spironolactone in Patients with CKD

• The safety and tolerability of spironolactone in patients with heart failure and CKD have been evaluated, and the results suggest that spironolactone may be safe to initiate in hospitalized patients with HF and CKD 5.
• However, the risk of hyperkalemia-associated hospitalization was higher in patients with CKD stage 3, and strategic treatments to prevent hyperkalemia should be enforced 6.
• A dose-response relationship was found between spironolactone use and risk of ESRD and hyperkalemia-associated hospitalization in patients with stage 3-4 CKD 6.

Long-Term Effects of Spironolactone on Kidney Function

• The long-term effects of spironolactone on kidney function and hyperkalemia-associated hospitalization in patients with CKD have been evaluated, and the results suggest that spironolactone may retard CKD progression to ESRD 6.
• However, the risk of hyperkalemia-associated hospitalization was higher in patients taking spironolactone, and careful monitoring of potassium levels is necessary 6.