From the Guidelines
The most common nephrotoxic drugs include aminoglycoside antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), ACE inhibitors and ARBs, certain chemotherapeutic agents, contrast media, calcineurin inhibitors, amphotericin B, vancomycin, and acyclovir, which can cause kidney damage through various mechanisms, including direct tubular toxicity, altered hemodynamics, crystal formation, or immune-mediated injury, as reported in the 2020 Kidney International study 1.
Nephrotoxic Drugs and Their Mechanisms
These medications can damage the kidneys through different mechanisms, including:
- Direct tubular toxicity, as seen with aminoglycosides, which accumulate in renal tubular cells causing direct damage 1
- Altered hemodynamics, as seen with NSAIDs, which reduce prostaglandin production, decreasing renal blood flow 1
- Crystal formation, as seen with certain chemotherapeutic agents, such as methotrexate 1
- Immune-mediated injury, as seen with immune checkpoint inhibitors, which can cause acute kidney injury (AKI) and proteinuria 1
High-Risk Patients and Prevention Strategies
Patients with pre-existing kidney disease, diabetes, heart failure, advanced age, or dehydration are at higher risk for drug-induced nephrotoxicity 1. To minimize kidney damage, the following strategies can be employed:
- Monitoring kidney function through serum creatinine and estimated glomerular filtration rate is essential when using these medications, especially in high-risk patients 1
- Dose adjustments, adequate hydration, and avoiding combinations of nephrotoxic drugs can help minimize kidney damage 1
- Drug stewardship, with a primary goal of balancing the changing risks and benefits of drug utilization and dosing in AKI/AKD, is critical in preventing or mitigating drug-associated kidney injury or dysfunction 1
From the FDA Drug Label
As with other aminoglycosides, gentamicin injection is potentially nephrotoxic. Concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs, such as cisplatin, cephaloridine, kanamycin, amikacin, neomycin, polymyxin B, colistin, paromomycin, streptomycin, tobramycin, vancomycin and viomycin, should be avoided.
The most common nephrotoxic drugs include:
- Aminoglycosides: such as gentamicin, kanamycin, amikacin, neomycin, streptomycin, and tobramycin
- Other nephrotoxic agents: such as cisplatin, cephaloridine, polymyxin B, colistin, paromomycin, vancomycin, and viomycin 2
From the Research
Nephrotoxic Drugs
The following are some of the most common nephrotoxic drugs:
- Antimicrobials, antihypertensives, and nonsteroidal anti-inflammatory drugs (NSAIDs) are common offenders of drug-induced kidney injury 3
- Immunosuppressive medications, statins, proton pump inhibitors, and herbal supplements can also cause kidney damage 3
- NSAIDs, diuretics, ACE inhibitors, and angiotensin II receptor blockers (ARBs) are the most frequent prerenal causes of an acute elevation in creatinine levels 4
- Aminoglycosides, vancomycin, and radiocontrast agents can cause tubulopathies 4
- Cyclosporin, tacrolimus, and muromonab-CD3 can cause primary vascular damage 4
Drug-Specific Nephrotoxicity
- Aminoglycosides are associated with nephrotoxicity, especially in older patients, and can cause acute kidney injury (AKI) 5, 6
- NSAIDs can lead to AKI, especially in the elderly, and can also cause chronic kidney disease (CKD) with long-term use 7, 6
- Cyclosporin can cause vasoconstriction of the afferent arteriole, leading to a lower glomerular filtration rate (GFR), and can also result in nephrotoxicity in combination therapy 6