Can intravenous (IV) cefazolin cause Acute Kidney Injury (AKI)?

Can IV Cefazolin Cause Acute Kidney Injury?

Yes, IV cefazolin can cause acute kidney injury (AKI), though it is generally less nephrotoxic than alternative anti-staphylococcal agents like nafcillin. The FDA drug label explicitly states that "reports of increased BUN and creatinine levels, as well as renal failure, have been received" with cefazolin use 1.

Mechanisms of Cefazolin-Associated AKI

Cefazolin can cause kidney injury through two primary mechanisms:

• Acute interstitial nephritis (AIN): The most common pathological finding, characterized by allergic tubular injury with sterile pyuria, eosinophiluria, and occasionally nephrotic-range proteinuria 1, 2
• Direct tubular toxicity: Particularly in patients with impaired renal function where drug accumulation occurs 1, 3

Incidence and Risk Profile

The risk of cefazolin-induced AKI is significantly lower compared to nafcillin:

• Cefazolin monotherapy: AKI incidence of approximately 2-13% depending on patient population 4, 5
• Nafcillin comparison: Nafcillin causes AKI in 19-33% of patients, making it 2.7-fold more likely to cause kidney injury (adjusted OR = 2.74; 95% CI 1.1-6.6) 6, 5
• Combination therapy risk: When cefazolin is combined with vancomycin, AKI risk increases to 13% versus 8% with cefazolin alone (adjusted OR = 1.82; 95% CI 1.25-2.64) 4

High-Risk Patient Populations

Certain patients face substantially elevated risk of cefazolin-associated AKI:

• Pre-existing chronic kidney disease: Independent risk factor (adjusted OR = 1.81; 95% CI 1.30-2.52) 4
• Malnourished patients: Particularly vulnerable to cefazolin-related coagulopathy and nephrotoxicity 3
• Patients with impaired renal function: Risk of drug accumulation and inappropriately high doses leading to seizures and kidney injury 1
• Higher ASA classification: Independent predictor of AKI (adjusted OR = 1.64; 95% CI 1.24-2.17) 4

Clinical Presentation and Timing

When cefazolin causes AKI, the presentation follows a predictable pattern:

• Time to onset: Typically occurs after prolonged therapy, with cases reported after 4 weeks of treatment 2
• Clinical features: Sterile pyuria with 3+ proteinuria, eosinophiluria, elevated serum creatinine, and occasionally nephrotic syndrome with protein excretion up to 7.95 g/day 2
• Severity: Most cases are mild and reversible, though some patients develop nephrotic-range proteinuria that may not fully recover to baseline 2

Prevention and Monitoring Strategies

Patients receiving cefazolin should have kidney function monitored regularly, particularly those with pre-existing risk factors 7, 8:

• Dose adjustment required: Lower daily dosage must be used in patients with impaired renal function to prevent drug accumulation 1
• Avoid combination nephrotoxins: The "triple whammy" effect applies—adding vancomycin to cefazolin nearly doubles AKI risk 4
• Monitor for early signs: Check serum creatinine, urinalysis for pyuria/eosinophiluria, and assess for fluid retention or edema 7, 2
• Duration minimization: Use cefazolin only for as long as clinically necessary, as prolonged courses increase toxicity risk 7, 8

Management of Cefazolin-Induced AKI

Immediate discontinuation of cefazolin is the primary intervention when AKI develops 9:

• Cessation leads to stabilization: Creatinine typically stabilizes within 2-3 days after stopping cefazolin 2
• Corticosteroid therapy: Prednisone 60 mg daily for 10 days with a 2-week taper may be beneficial for acute interstitial nephritis, though recovery may be incomplete 2
• Recovery timeline: Most patients show improvement within days to weeks, though some residual dysfunction may persist 2

Critical Clinical Pitfall

Do not avoid cefazolin in life-threatening MSSA infections solely due to AKI concern—the drug should not be withheld when clinically indicated, but monitoring must be intensified 7. However, for elective procedures or non-critical infections in high-risk patients (pre-existing CKD, malnutrition, concurrent nephrotoxins), strongly consider the risk-benefit ratio and implement aggressive monitoring protocols 8, 4.