Is cefazolin (a first-generation cephalosporin antibiotic) nephrotoxic?

Nephrotoxicity of Cefazolin

Cefazolin has a relatively low risk of nephrotoxicity compared to other antibiotics, but it can cause renal adverse effects, particularly in patients with pre-existing renal impairment, where dose adjustment is essential to prevent toxicity.

Nephrotoxicity Profile of Cefazolin

Evidence from Drug Label and Guidelines

• The FDA drug label for cefazolin specifically lists renal adverse effects, stating: "reports of increased BUN and creatinine levels, as well as renal failure, have been received" 1
• Cefazolin is primarily cleared by glomerular filtration, with tubular and biliary secretion playing a secondary role 2
• Among beta-lactam antibiotics, cefazolin has a higher pro-convulsive activity (294 relative to penicillin G's 100), which can manifest when the drug accumulates due to renal dysfunction 3

Risk Factors for Cefazolin Nephrotoxicity

• Pre-existing renal impairment: The most significant risk factor for cefazolin nephrotoxicity
• Inappropriate dosing: Failure to adjust doses in patients with renal dysfunction
• Advanced age: Elderly patients may develop renal impairment more easily 3
• Concomitant nephrotoxic medications: Should be avoided when possible 3

Mechanisms of Cefazolin Nephrotoxicity

Cefazolin can affect the kidneys through several mechanisms:

• Direct tubular toxicity (most common)
• Interstitial nephritis (less common)
• Acute kidney injury due to drug accumulation in renal dysfunction

The pathogenesis is generally considered to be dose-related rather than hypersensitivity-mediated 4.

Clinical Manifestations of Cefazolin Nephrotoxicity

• Elevated BUN and creatinine levels
• Decreased glomerular filtration rate
• Acute interstitial nephritis (AIN), sometimes with nephrotic-range proteinuria 5
• In severe cases, renal failure requiring intervention

Prevention of Cefazolin Nephrotoxicity

Dose Adjustment

• Dose adjustment is crucial in patients with impaired renal function 6
• The serum half-life of cefazolin in patients with normal renal function is approximately 1.6 hours but can be prolonged to about 42 hours in anephric patients 2

Monitoring Recommendations

• Regular monitoring of renal function during therapy
• More frequent monitoring in high-risk patients (elderly, pre-existing renal disease)
• Consider therapeutic drug monitoring in patients with significant renal impairment

Comparison with Other Antibiotics

• Cefazolin is generally less nephrotoxic than aminoglycosides, which are known for their nephrotoxicity 3
• Among cephalosporins, newer generations are generally considered to have a lower incidence of nephrotoxicity than earlier generations 4
• When considering alternatives in patients with renal dysfunction, avoid aminoglycoside antibiotics and tetracyclines due to their nephrotoxicity 3

Management of Cefazolin-Induced Nephrotoxicity

If nephrotoxicity is suspected:

1. Evaluate renal function immediately
2. Consider dose reduction or discontinuation of cefazolin
3. Avoid concomitant nephrotoxic drugs
4. Ensure adequate hydration
5. Monitor renal function closely until resolution

Special Considerations

• Patients on dialysis: Require specific dose adjustments and timing relative to dialysis sessions
• Elderly patients: May require lower initial doses and more careful monitoring
• Patients with multiple comorbidities: Higher risk of drug interactions and additive nephrotoxicity

In conclusion, while cefazolin is not among the most nephrotoxic antibiotics, it does carry a risk of renal adverse effects that increases significantly in patients with pre-existing renal dysfunction. Appropriate dose adjustment and monitoring of renal function are essential to minimize this risk.