Incidence and predictors of intravenous acyclovir-induced nephrotoxicity

Abstract

To assess the incidence, predictive factors, and prognosis of acyclovir-induced nephrotoxicity. We conducted a historical prospective cohort study of patients treated with intravenous acyclovir in North Denmark Region from 2009 to 2016. Information on baseline demographics, co-morbidities, plasma creatinine, and treatment was obtained from the medical records. The primary outcome was an increase of ≥ 40 μmol/L in plasma creatinine level from baseline. We included 276 patients treated with intravenous acyclovir of which 29 (10.5%) met the primary outcome. In 14 cases, the treating physician considered acyclovir the main reason for nephrotoxicity, whereas a potential competing cause of renal impairment was present among the 15 remaining patients. Hypertension was the only predictive factor associated with nephrotoxicity (risk ratio (RR), 2.77; 95% confidence interval (CI), 1.41-5.46), while having no co-morbidities was protective (RR, 0.32; CI, 0.16-0.63). In all cases, the nephrotoxicity was reversible following rehydration and dose reduction or discontinuation of the drug. However, the normalized plasma creatinine upon treatment was significantly higher between cases with acyclovir-induced nephrotoxicity than cases with a potential competing cause (median [interquartile range (IQR)], 93.5 μmol/L [85-108] vs 75 μmol/L [66.5-88]; p = 0.019). Acyclovir-induced, reversible nephrotoxicity was observed in 5.1-10.5% of patients. It is difficult to predict who will develop acyclovir-induced nephrotoxicity; it may occur late in treatment and hypertension was the only independent predictive factor, while the absence of co-morbidities was protective. Ensuring hydration, frequent evaluations of renal function, and corresponding dose adjustment of intravenous acyclovir treatment seem prudent.

Outcomes with acyclovir treatment in herpes simplex encephalitis after surgery for solid CNS tumors: a case report and systematic review of the literature

“…Literature review found that a delay in recognition and treatment may result in severe morbidity: Nephrotoxicity developed in only 5% to 10% of the cases in a prospective cohort of 276 patients. 13 In conclusion, HSE may develop following neurosurgical resection and the threshold for suspicion of HSE should be extremely low in a patient who shows compatible symptoms (encephalopathy, fever, and seizures) or does not recover as planned. Moreover, in case of suspicion of HSE, acyclovir should be promptly started until infection can be definitely ruled out.…”

“…There have been case reports of acute kidney injury precipitated by acyclovir, 11,12 though a prospective cohort study of 276 patients showed acyclovir-induced nephrotoxicity in only 5% to 10% of cases, all of which were reversible with IV hydration, dose reduction, or discontinuation of the drug. 13 The use of antivirals may reduce morbidity and mortality of HSE, whether it occurs by latent reactivation or primary infection 3 ; and given the life-threatening nature of HSE, the benefits of treatment may outweigh the risk of untreated disease or potential nephrotoxicity of acyclovir, which could be avoided by adequate hydration and renally adjusting the dose.…”

Acute Renal Failure Related to High Doses of Acyclovir (15 mg/kg/8 h) during Treatment of Varicella Zoster Virus Encephalitis

“…Acyclovir is a nephrotoxic drug often implicated in ARF [6,7] by a mechanism of precipitation (crystals) and acute tubular necrosis. Reports of ARF are frequent [8][9][10][11][12][13] and are accompanied by classical risk factors: high dose administration, water-soluble depletion and combination with other nephrotoxic drugs, leading to a recommendation for slow infusion administration with hydration. In patients with renal insufficiency, dosage reduction is required.…”

Acyclovir for ventilator-associated pneumonia refractory to antibiotics and with high viral herpes simplex load: we are not sure

“…In a recently published trial, IV acyclovir treatment at 5 mg/kg TID was considered safe, with no difference in renal failure, creatinine increase, and renal replacement therapy rates compared to the placebo group [6]. Richelsen et al described nephrotoxicity in 5.1-10.5% of patients receiving 10 mg/kg acyclovir TID, which was fully reversible [7]. Moreover, older studies already showed that nephrotoxicity was usually reversible and could be minimised by slow infusion and adequate hydration [8].…”