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Initial administration of glucocorticoids
3%
14/464
Monitoring of drug levels
16/464
Obtaining a thorough history of patient allergies
1%
4/464
Adequate initial hydration
77%
356/464
Initial administration of allopurinol
14%
67/464
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This patient with shingles is treated with IV acyclovir and subsequently develops acute renal failure secondary to crystalline nephropathy. Adequate initial hydration can reduce the risk of crystalline nephropathy. Acyclovir is a nucleoside analogue that requires a virus specific thymidine kinase for activation. It inhibits viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and incorporating with viral DNA where it causes termination of synthesis. Acyclovir has a relatively low solubility and can crystallize in the tubular lumen due to the concentrating effects of filtration and secretion into this space. This results in renal tubular damage and can be avoided, as well as treated, with adequate hydration or a decreased rate of administration. According to Naughton et al., the likelihood of crystal precipitation increases as urine concentration of acyclovir increases, so those who are volume depleted or have underlying renal insufficiency are at greatest risk of crystal nephropathy. According to Gunness et al., there is an additional mechanism of nephrotoxicity, which involves metabolism of acyclovir in the tubular lumen. There is some evidence to suggest that acyclovir aldehyde, a metabolite produced in cells from proximal tubule epithelial wall, is the pathogen responsible for causing renal tubular destruction. Incorrect Answers: Answer 1: Initial therapy with glucocorticoids such as prednisone are used to decrease risk of allergies to radiocontrast, but would not help acyclovir-induced crystalline nephropathy. Answer 2: Acyclovir may precipitate even at low blood levels if the patient is volume depleted owing to a low luminal flow rate and therefore an increased concentration of acyclovir in this compartment. Answer 3: An allergic reaction is unlikely to cause crystalline nephropathy. Answer 5: Allopurinol pretreatment does prevent crystalline nephropathy but in the setting of tumor-lysis syndrome secondary to lymphoma/leukemia treatment, but is not beneficial in disease caused by acyclovir.
3.3
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