From the Guidelines
Acyclovir-induced renal toxicity is primarily caused by crystalluria, leading to obstructive nephropathy.
Mechanism of Renal Toxicity
The mechanism of Acyclovir-induced renal toxicity is attributed to its excretion by the kidneys, where it can cause renal impairment through crystalluria, resulting in obstructive nephropathy 1. This reversible nephropathy usually manifests after 4 days of intravenous therapy and can affect up to 20% of patients 1, 2.
Risk Factors and Prevention
The risk of nephropathy can be reduced by maintaining adequate hydration and monitoring renal function 2. Additionally, the dose of acyclovir should be reduced in patients with pre-existing renal impairment, as it is excreted via the kidneys 2.
Clinical Considerations
In patients with suspected viral encephalitis, acyclovir treatment is usually started once the initial CSF and/or imaging findings suggest viral encephalitis, without waiting for confirmation of HSV by PCR 1, 2. However, clinicians should be aware of the potential for renal toxicity and take steps to prevent it, such as adequate hydration and monitoring of renal function.
Dosage Adjustments
Dosage adjustments for acyclovir in patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD) are recommended, with reduced doses for patients with creatinine clearance <10 mL/min 3.
From the FDA Drug Label
Precipitation of acyclovir in renal tubules may occur when the solubility (2.5 mg/mL) is exceeded in the intratubular fluid. The mechanism of Acyclovir-induced renal toxicity is precipitation of acyclovir in renal tubules when the solubility is exceeded in the intratubular fluid, leading to potential renal failure 4.
- Key factors contributing to this mechanism include: + High doses or bolus injections + Inadequate fluid and electrolyte balance + Exceeding the solubility limit of 2.5 mg/mL in the intratubular fluid
From the Research
Mechanism of Acyclovir-Induced Renal Toxicity
The mechanism of acyclovir-induced renal toxicity is complex and involves multiple factors. Some studies suggest that:
- Acyclovir crystalluria, which leads to an intraparenchymal form of obstructive nephropathy, is a primary cause of nephrotoxicity 5, 6
- Direct renal tubular toxicity, mediated by the acyclovir aldehyde metabolite, may also play a role in acyclovir-induced nephrotoxicity 7
- Metabolic changes, including alterations in urinary metabolites such as guanine, 4-guanidinobutyric acid, creatinine, and urea, may be involved in the development of nephrotoxicity 8
Key Factors Contributing to Nephrotoxicity
Several factors have been identified as contributing to the development of acyclovir-induced nephrotoxicity, including:
- Age: older patients are more susceptible to nephrotoxicity 9
- Dose: higher doses of acyclovir increase the risk of nephrotoxicity 9
- Concomitant use of nephrotoxic drugs: increases the risk of nephrotoxicity 9, 6
- Duration of treatment: longer treatment durations increase the risk of nephrotoxicity 9
Pathological Changes
The pathological changes associated with acyclovir-induced nephrotoxicity include: