Nephrotoxic Drugs: Comprehensive List
The most clinically significant nephrotoxic drugs include NSAIDs, aminoglycosides, ACE inhibitors/ARBs, contrast media, calcineurin inhibitors, and chemotherapeutic agents, with the "triple whammy" combination of NSAIDs + diuretics + ACE inhibitors/ARBs more than doubling acute kidney injury risk. 1
High-Risk Nephrotoxic Drug Categories
Antimicrobials
- Aminoglycosides (gentamicin, tobramycin, amikacin, kanamycin, neomycin, streptomycin, paromomycin) cause direct tubular toxicity and increase AKI odds by 53%, with risk compounding when combined with other nephrotoxins 1, 2, 3
- Vancomycin causes nephrotoxicity particularly at prolonged peak concentrations above 12 mcg/mL and trough levels above 2 mcg/mL 4, 2
- Amphotericin B has preferential nephrotoxicity potential through direct tubular injury 5
NSAIDs and Analgesics
- All NSAIDs including COX-2 inhibitors cause renovasoconstriction and precipitate AKI, especially in patients with pre-existing kidney insufficiency or diminished kidney blood flow 4, 1
- Naproxen specifically increases AKI risk in patients with UTIs through prostaglandin synthesis inhibition and interstitial nephritis 6
Cardiovascular Medications
- ACE inhibitors and ARBs (renin-angiotensin-aldosterone antagonists) alter intraglomerular hemodynamics through efferent arteriole dilation, decreasing renal perfusion pressure 4, 1
- α1-adrenoceptor antagonists affect renal hemodynamics 4
- Potent diuretics (ethacrynic acid, furosemide) cause ototoxicity and enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue 2
Chemotherapeutic and Immunosuppressive Agents
- Calcineurin inhibitors (cyclosporine A, tacrolimus) cause direct nephrotoxicity 4, 1, 5
- Cisplatin has preferential nephrotoxicity potential through direct tubular injury 4, 5
- Tyrosine kinase inhibitors cause tubulointerstitial injury 4
- BRAF inhibitors cause tubulointerstitial injury and AKI 4
- Proteasome inhibitors may be associated with thrombotic microangiopathy 4
- Immune checkpoint inhibitors cause AKI primarily through acute interstitial nephritis and acute tubular injury 4
- Methotrexate causes crystalline nephropathy through tubular obstruction 4
Contrast and Diagnostic Agents
- IV or intra-arterial contrast media cause nephrotoxicity especially in patients with pre-existing kidney dysfunction such as diabetic nephropathy 4, 1
- Radiolabeled somatostatin analogs accumulate in kidneys via megalin and cubilin-mediated endocytosis 7
Other Nephrotoxic Agents
- Polymyxin B and colistin cause direct tubular toxicity 2
- Cephaloridine (first-generation cephalosporin) has nephrotoxic potential 2
- Viomycin causes nephrotoxicity 2
Mechanisms of Nephrotoxicity
Direct Tubular Toxicity
- Aminoglycosides, cisplatin, and amphotericin B cause acute tubular necrosis through direct cellular injury 3, 8
- Drugs accumulate in proximal tubular cells via specific transport systems, leading to concentrated retention and toxicity 7
Hemodynamic Alterations
- NSAIDs cause afferent arteriole constriction reducing renal perfusion 1
- ACE inhibitors/ARBs cause efferent arteriole dilation decreasing glomerular filtration pressure 1
- Medications causing systemic hypotension reduce kidney perfusion 1
Immune-Mediated Injury
- Acute interstitial nephritis occurs through type IV delayed-type hypersensitivity response, commonly with antibiotics and immune checkpoint inhibitors 4, 8
Crystal Formation and Obstruction
Thrombotic Microangiopathy
High-Risk Drug Combinations
The "Triple Whammy"
- NSAIDs + diuretics + ACE inhibitors/ARBs more than doubles AKI risk, with 25% of non-critically ill patients developing AKI when receiving three or more nephrotoxins 1
Statin Interactions
- Macrolide antibiotics + statins increase AKI risk from rhabdomyolysis due to impaired statin clearance via CYP3A4 inhibition 1
Multiple Nephrotoxin Exposure
- Escalating from two to three nephrotoxic medications more than doubles AKI risk 1
- Concurrent use of cisplatin, cephaloridine, kanamycin, amikacin, neomycin, polymyxin B, colistin, paromomycin, streptomycin, tobramycin, vancomycin, and viomycin should be avoided 2
Risk Factors for Drug-Induced Nephrotoxicity
Patient-Specific Factors
- Pre-existing chronic kidney disease significantly increases vulnerability 1, 3
- Advanced age increases toxicity risk 2
- Diabetes mellitus increases risk of drug-induced nephrotoxicity 1
- Dehydration compounds nephrotoxicity risk 2
- Previous history of AKI elevates risk 1
- Hypercalcemia increases nephrotoxicity risk 1
Prevention Strategies
Medication Management
- Administer potentially nephrotoxic medications only when needed and for the shortest duration possible 1
- Use less nephrotoxic alternatives: acetaminophen for non-inflammatory pain instead of NSAIDs 1
- Avoid NSAIDs entirely in patients with pre-existing kidney insufficiency or diminished kidney blood flow 1
- Consider low-dose opiates or short courses of corticosteroids for inflammatory conditions 1
Monitoring Requirements
- Monitor kidney function (serum creatinine, BUN, creatinine clearance) in all patients exposed to nephrotoxic agents 1, 2
- Examine urine for decreased specific gravity, increased protein excretion, and presence of cells or casts 2
- Monitor aminoglycoside peak and trough levels to avoid prolonged concentrations above 12 mcg/mL and trough levels above 2 mcg/mL 1, 2
- Obtain serial audiograms in high-risk patients when feasible 2
- Monitor serum creatinine, BUN, urine output, and electrolytes in patients exposed to multiple nephrotoxins 6
Hydration and Prophylaxis
- Ensure adequate hydration, especially when administering contrast media or other high-risk agents 1
- Consider N-acetylcysteine before contrast studies in high-risk patients 1
Patient Education
- Educate patients to avoid over-the-counter NSAIDs during UTI episodes and other high-risk situations 6
- Instruct patients to consult before taking new medications, particularly decongestants, antivirals, antibiotics, and herbal products 1