What are common nephrotoxic (kidney damaging) drugs?

From the Guidelines

Nephrotoxic drugs that can damage the kidneys include nonsteroidal anti-inflammatory drugs (NSAIDs), aminoglycoside antibiotics, certain chemotherapeutic agents, calcineurin inhibitors, and contrast media, among others, as highlighted in a recent study 1.

Common Nephrotoxic Drugs

Some of the common nephrotoxic drugs are:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, and diclofenac, which can impair renal blood flow by inhibiting prostaglandin synthesis
• Aminoglycoside antibiotics like gentamicin, tobramycin, and amikacin, which accumulate in renal tubular cells and cause direct cellular toxicity
• Certain chemotherapeutic agents, including platinum-containing compounds (especially cisplatin), ifosfamide, gemcitabine, methotrexate, and pemetrexed, as noted in a study on the nephrotoxicity of oncologic treatments 1
• Calcineurin inhibitors (cyclosporine, tacrolimus), amphotericin B, vancomycin, and acyclovir, which can also cause kidney damage

Risk Factors for Nephrotoxicity

Risk factors for drug-induced kidney injury include:

• Advanced age
• Pre-existing kidney disease
• Dehydration
• Concurrent use of multiple nephrotoxic agents

Management of Nephrotoxicity

When prescribing these medications, appropriate dosing, hydration status monitoring, and regular assessment of kidney function are essential to minimize the risk of nephrotoxicity 1. It is also important to consider the benefits versus potential harms of medications in people with chronic kidney disease (CKD) and to monitor eGFR, electrolytes, and therapeutic medication levels, when indicated, in people with CKD receiving medications with narrow therapeutic windows, potential adverse effects, or nephrotoxicity 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. Amphotericin B should be used with care in patients with reduced renal function; frequent monitoring of renal function is recommended Other nephrotoxic medications: agents such as aminoglycosides, cyclosporine, and pentamidine may enhance the potential for drug-induced renal toxicity, and should be used concomitantly only with great caution. Monitor renal function in patients receiving vancomycin and concurrent and/or sequential systemic or topical use of other potentially, neurotoxic and/or nephrotoxic drugs, such as amphotericin B, aminoglycosides, bacitracin, polymyxin B, colistin, viomycin, or cisplatin

Common nephrotoxic drugs include:

• Aminoglycosides (e.g. gentamicin, kanamycin, amikacin, neomycin, streptomycin, tobramycin) 2
• Amphotericin B 3
• Vancomycin 4
• Cisplatin
• Cyclosporine
• Pentamidine
• Bacitracin
• Polymyxin B
• Colistin
• Viomycin
• Cephaloridine
• Paromomycin

From the Research

Nephrotoxic Drugs

• Drugs known to be nephrotoxic include:
  • Cancer therapeutics 5
  • Drugs of abuse 5
  • Antibiotics, such as vancomycin, aminoglycosides, and beta lactamines 6, 7, 8
  • Radiocontrast agents 5, 9
• Other nephrotoxic substances include:
  • Environmental pollutants, such as cadmium, mercury, arsenic, lead, trichloroethylene, bromate, brominated-flame retardants, diglycolic acid, and ethylene glycol 5
  • Natural nephrotoxicants, such as aristolochic acids and mycotoxins like ochratoxin, fumonisin B1, and citrinin 5

Mechanisms of Nephrotoxicity

• Mechanisms of antibiotic-induced nephrotoxicity include:
  • Glomerular injury 8
  • Tubular injury or dysfunction 8
  • Distal tubular obstruction from casts 8
  • Acute interstitial nephritis (AIN) mediated by a type IV (delayed-type) hypersensitivity response 8
• Clinical manifestations of antibiotic-induced nephrotoxicity include:
  • Acute tubular necrosis (ATN) 8
  • AIN 8
  • Fanconi syndrome 8

Risk Factors and Prevention

• General risk factors for antimicrobial-induced acute kidney injury (AKI) include:
  • Pre-existing chronic kidney disease 6
  • Concomitant use of medication with nephrotoxic potential 6
• Prevention and early recognition of AKI represent the standard approach to mitigate AKI and avoid morbidity 6
• Use of novel biomarkers, such as cystatin C and urinary kidney injury molecule-1 (KIM-1), may result in earlier detection of AKI, dose adjustment, or discontinuation of antibiotic 8