What medications are nephrotoxic and need to be temporarily ceased in the context of acute kidney injury (AKI)?

Nephrotoxic Medications to Temporarily Cease in Acute Kidney Injury

In the context of acute kidney injury (AKI), several potentially nephrotoxic medications should be temporarily discontinued to prevent further kidney damage and promote recovery. 1

Primary Medications to Cease in AKI

• Renin-Angiotensin-Aldosterone System (RAAS) Blockers:

  • ACE inhibitors (e.g., lisinopril, enalapril)
  • Angiotensin receptor blockers (ARBs)
  • Aldosterone inhibitors
  • Direct renin inhibitors 1

• Diuretics (particularly loop diuretics like furosemide) should be temporarily discontinued or doses adjusted, as they are associated with the largest risk of worsening AKI (HR 1.64) 2

• Non-steroidal anti-inflammatory drugs (NSAIDs) should be immediately stopped as they reduce renal perfusion 1

• Metformin should be discontinued in patients with GFR <30 ml/min/1.73m² (GFR categories G4-G5) and reviewed in those with GFR 30-44 ml/min/1.73m² 1

• Lithium requires discontinuation and monitoring of drug levels 1

• Digoxin should be temporarily ceased due to risk of toxicity with reduced renal clearance 1

Antibiotics and Antimicrobials with Nephrotoxic Potential

• Aminoglycosides (e.g., gentamicin):

  • Particularly nephrotoxic with risk increasing with prolonged therapy
  • Concurrent use with other nephrotoxic agents significantly increases risk 3

• Vancomycin:

  • Associated with acute kidney injury, especially with high serum levels
  • Risk increases with concurrent nephrotoxic medications 4
  • Identified as the primary nephrotoxin in many cases of drug-induced AKI 5

• Trimethoprim-sulfamethoxazole should be avoided if creatinine clearance is <15 ml/min 1

• Amphotericin B has significant nephrotoxic potential 5

Contrast Media and Imaging Agents

• Iodinated radiocontrast media should be avoided when possible

  • If essential, use lowest possible dose and ensure adequate hydration
  • High osmolar agents should be particularly avoided 1

• Gadolinium-based contrast media should not be used in people with GFR <15 ml/min/1.73m² 1

Combination Risks

• The "triple whammy" combination (NSAIDs + diuretics + ACE inhibitors/ARBs) dramatically increases AKI risk and should be avoided 1

• Escalating from two to three nephrotoxic medications more than doubles the risk of developing AKI 1

• Certain drug interactions increase nephrotoxicity risk:

  • Some macrolide antibiotics (clarithromycin, erythromycin) with statins can lead to rhabdomyolysis and subsequent AKI 1
  • Concurrent use of aminoglycosides with other nephrotoxic drugs significantly increases risk 3

Monitoring and Management Approach

1. Identify all potentially nephrotoxic medications in the patient's regimen 1

2. Assess the necessity of each medication:

   • Is the drug essential for immediate patient care?
   • Are there less nephrotoxic alternatives available? 1

3. Consider drug-specific factors:

   • Renal versus non-renal excretion
   • Potential for direct nephrotoxicity
   • Effect of AKI on drug metabolites 1

4. Resume medications cautiously after kidney function improves, with close monitoring of renal function 1

Special Considerations

• Over-the-counter medications and herbal remedies should also be discontinued, as they may contain nephrotoxic compounds 1

• Calcineurin inhibitors (e.g., cyclosporine, tacrolimus) require drug level monitoring and possible dose adjustment 1

• For cancer patients, cytotoxic drugs should have appropriate dose adjustment according to GFR rather than complete discontinuation 1

By promptly identifying and temporarily discontinuing nephrotoxic medications in the setting of AKI, clinicians can help prevent further kidney damage and promote recovery of renal function 1, 6, 7.