Acyclovir-Induced Kidney Injury
Acyclovir causes reversible nephrotoxicity in up to 20% of patients receiving intravenous therapy, typically manifesting after 4 days of treatment through crystalluria and obstructive nephropathy, which can be prevented by slow infusion over at least 1 hour, maintaining adequate hydration, and adjusting doses for any degree of renal impairment. 1, 2
Mechanism and Timing of Injury
The nephrotoxicity occurs through crystal formation in renal tubules and collecting ducts, as acyclovir is predominantly excreted by the kidneys. 1, 3 The injury typically develops within 24-48 hours of administration, characterized by a rapid rise in serum creatinine. 4, 5 However, the most common presentation is after 4 days of intravenous therapy. 1, 2
Risk Factors for Nephrotoxicity
Patients at substantially increased risk include:
- Those with pre-existing renal impairment, who require mandatory dose adjustment 1, 6
- Patients receiving rapid IV bolus injections rather than slow infusions 3
- Dehydrated patients or those with water restriction 4, 7, 3
- Patients receiving high doses (particularly above standard dosing) 7
- Those on concurrent nephrotoxic medications 6
Prevention Strategies
The following measures are essential to minimize nephrotoxicity risk:
- Never administer acyclovir as a rapid IV bolus; always infuse slowly over at least 1 hour 2, 3
- Maintain adequate hydration throughout therapy 1, 6
- Calculate IV acyclovir doses based on ideal body weight 2
- Monitor renal function at initiation and once or twice weekly during treatment 1
- Perform regular renal function assessments within the first 48 hours of treatment for early detection 4
Dose Adjustments for Renal Impairment
Mandatory dose reductions based on creatinine clearance: 6
| Creatinine Clearance | Oral Dosing Adjustment | IV Dosing Adjustment |
|---|---|---|
| >25 mL/min | Standard dosing | Standard dosing |
| 10-25 mL/min | Every 8 hours | Every 12-24 hours |
| <10 mL/min | Every 12 hours | 2.5-5 mg/kg every 24 hours |
| Hemodialysis | After dialysis | 2.5-5 mg/kg every 24 hours, dosed after dialysis |
The dose of acyclovir must be reduced in patients with pre-existing renal impairment because it is excreted via the kidneys. 1
Management of Established Nephrotoxicity
When acyclovir-induced nephrotoxicity is suspected:
Renal function typically improves rapidly within 24 hours to 1 week after discontinuation and rehydration. 4, 7, 8 This nephropathy is reversible, with crystals being removed after cessation of treatment. 3
Clinical Presentation
Patients may present with:
- Elevated BUN and serum creatinine (often the only findings) 8
- Mild proteinuria 8
- Normal urine output in many cases 8
- Decreased GFR by >25% from baseline 1
Additional Serious Adverse Effects
Beyond nephrotoxicity, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has been reported in immunocompromised patients, resulting in death in some cases, though this is rare. 1, 2 This complication has been specifically associated with high-dose valacyclovir (8 grams/day) but not at standard HSV treatment doses. 1
Special Considerations
In patients with chronic kidney disease requiring acyclovir: The risk must be balanced against treatment necessity, particularly for life-threatening conditions like HSV encephalitis where delayed treatment beyond 48 hours worsens outcomes. 1 In such cases, use reduced doses appropriate for creatinine clearance, avoid concurrent nephrotoxic drugs, and monitor renal function intensively. 1
Common pitfall: Failing to adjust doses in elderly patients, who have higher plasma concentrations due to age-related renal function decline. 6 Dosage reduction may be required in geriatric patients with underlying renal impairment. 6