What are the most common medications that cause acute kidney injury (AKI), grouped by category?

Common Medications That Cause Acute Kidney Injury by Category

The most common medications that cause acute kidney injury can be classified into four categories based on their mechanism of action: those causing dysfunction without injury, those causing injury without dysfunction, those causing both dysfunction and injury, and those with minimal direct effects on kidney function.

1. Medications Causing Both Dysfunction and Injury

• Nonsteroidal Anti-inflammatory Drugs (NSAIDs) are among the most common causes of AKI, affecting both kidney function through altered hemodynamics and causing direct tubular injury 1, 2
• The "triple whammy" combination of NSAIDs with diuretics and ACE inhibitors/ARBs significantly increases AKI risk through synergistic effects on kidney perfusion 1, 2
• NSAIDs in combination products (e.g., oxycodone-acetaminophen) can cause kidney dysfunction through systemic hypotension and intraglomerular hemodynamic alterations 2

2. Medications Causing Dysfunction Without Injury

• Angiotensin-Converting Enzyme (ACE) Inhibitors alter intraglomerular hemodynamics by dilating the efferent arteriole, reducing glomerular filtration pressure 1
• Angiotensin Receptor Blockers (ARBs) function similarly to ACE inhibitors by affecting kidney hemodynamics without direct tubular damage 1
• Diuretics, particularly when causing volume depletion, can lead to prerenal AKI through reduced kidney perfusion 1, 3

3. Medications Causing Injury Without Dysfunction

• Aminoglycosides (e.g., gentamicin, tobramycin) cause direct tubular cell injury through filtered toxins accumulating in proximal tubular cells 1, 4
• Acyclovir can cause crystal nephropathy with intratubular precipitation leading to obstruction and injury 1, 5
• Vascular Endothelial Growth Factor (VEGF) Antagonists can cause direct glomerular injury 1
• Antimicrobials like vancomycin can cause acute interstitial nephritis or cast nephropathy 4, 5

4. Medications With Minimal Direct Effects

• Trimethoprim and cimetidine affect creatinine secretion without causing significant kidney dysfunction or injury 1

Risk Factors for Drug-Induced AKI

• Advanced age (>65 years) significantly increases susceptibility to drug-induced kidney injury 1, 2
• Pre-existing chronic kidney disease amplifies the risk of developing AKI from nephrotoxic medications 1, 6
• Concomitant use of multiple potentially nephrotoxic drugs ("drug burden") increases AKI risk synergistically 1, 2
• Dehydration or volume depletion states significantly enhance nephrotoxic potential of many medications 1, 2
• Diabetes mellitus increases susceptibility to drug-induced kidney injury 1, 3

Prevention Strategies

• Monitor kidney function regularly with serum creatinine and BUN measurements in patients receiving potentially nephrotoxic medications 1, 2
• Ensure adequate hydration, especially when using medications with high nephrotoxic potential 2, 6
• Use the lowest effective dose for the shortest duration necessary when nephrotoxic agents cannot be avoided 1, 6
• Implement drug stewardship programs to balance risks and benefits of drug utilization in patients at risk for AKI 1
• Watch for early signs of kidney injury such as decreased urine output, edema, or rising creatinine 2, 6

Special Considerations

• Potentially nephrotoxic agents should not be withheld in life-threatening conditions solely due to AKI concerns, including intravenous contrast when necessary 1
• Drug-induced kidney injury can occur through various mechanisms including direct tubular toxicity, altered hemodynamics, immune-mediated injury, and crystal nephropathy 2, 5
• The risk of kidney injury increases with duration of therapy and total drug burden 1, 2