What are the most common nephrotoxic medications?

Most Common Nephrotoxic Medications

Aminoglycosides, NSAIDs, and contrast media are the most common nephrotoxic medications that clinicians should be vigilant about when managing patients with or at risk for kidney injury. 1, 2

Major Classes of Nephrotoxic Medications

1. Antimicrobials

• Aminoglycosides (gentamicin, amikacin, tobramycin)

  • Cause direct tubular toxicity 3, 2
  • Risk of nephrotoxicity is greater in patients with impaired renal function and those receiving high doses or prolonged therapy 2
  • Monitoring recommendations: Check BUN, serum creatinine periodically; maintain trough levels below 2 mcg/mL for gentamicin 2

• Other antimicrobials

  • Vancomycin
  • Amphotericin B
  • Polymyxins (colistin)
  • Acyclovir (crystallization) 3

2. Anti-inflammatory Drugs

• NSAIDs
  • Cause hemodynamic changes in the kidney by blocking prostaglandin synthesis 1
  • Particularly risky in patients with pre-existing kidney disease 1
  • Can cause acute interstitial nephritis and renovasoconstriction 3

3. Cardiovascular Medications

• ACE inhibitors/ARBs

  • Affect renal hemodynamics, especially in volume-depleted states 3

• Diuretics (loop diuretics like torsemide, thiazides like metolazone)

  • Can reduce renal blood flow, especially in volume-depleted states 1
  • Potent diuretics (ethacrynic acid, furosemide) can enhance aminoglycoside toxicity when administered intravenously 2

4. Chemotherapeutic Agents

• Platinum compounds (especially cisplatin)

  • Cause acute tubular injury 3

• Other chemotherapeutics

  • Ifosfamide, gemcitabine, methotrexate, pemetrexed 3
  • Can cause various kidney lesions including thrombotic microangiopathy, tubulopathies, and crystalline nephropathy 3

5. Contrast Media

• Used in imaging studies
• Risk factors: pre-existing CKD, diabetes, dehydration 3

6. Targeted Cancer Therapies

• Anti-angiogenesis drugs

  • Associated with hypertension, proteinuria, and thrombotic microangiopathy 3

• Tyrosine kinase inhibitors

  • Can cause tubulointerstitial injury 3

• Immune checkpoint inhibitors

  • Primarily cause acute interstitial nephritis 3

Risk Factors for Drug-Induced Nephrotoxicity

1. Pre-existing kidney disease
2. Advanced age
3. Volume depletion/dehydration
4. Multiple nephrotoxic medications used concurrently
5. High doses or prolonged therapy
6. Sepsis or critical illness

Prevention Strategies

1. Avoid concurrent use of multiple nephrotoxic agents when possible 1
2. Ensure adequate hydration, especially when using diuretics or contrast media 1
3. Adjust dosing in patients with impaired renal function 3
4. Monitor kidney function regularly in high-risk patients 1
5. Use the lowest effective dose for the shortest duration necessary 4
6. Consider temporary discontinuation of nephrotoxic medications during acute illness 1

Monitoring Recommendations

1. Regular assessment of kidney function

   • Monitor serum creatinine, BUN, and GFR
   • Check urine for decreased specific gravity, protein, cells, or casts 2

2. Drug-specific monitoring

   • For aminoglycosides: Monitor serum drug concentrations; avoid peak levels above 12 mcg/mL and trough levels above 2 mcg/mL 2
   • For patients on multiple nephrotoxic drugs: More frequent monitoring of kidney function

3. Electrolyte monitoring

   • Particularly important with diuretics and certain antimicrobials
   • Special attention to magnesium levels with certain drugs (e.g., cetuximab) 3

By recognizing these common nephrotoxic medications and implementing appropriate monitoring and prevention strategies, clinicians can significantly reduce the risk of drug-induced kidney injury and improve patient outcomes.