LAUSR

To the Editor, We describe a patient with end-stage renal disease (ESRD) on hemodialysis (HD) who presented in an acute confusional state following treatment with oral aciclovir. The patient underwent hemodiafiltration (HDF), resulting in improvement of her neuropsychiatric symptoms and a more marked fall in her serum aciclovir levels than previously described with conventional HD. This is the first published description of aciclovir-induced neurotoxicity being treated with HDF. A 65-year-old female with ESRD secondary to autosomal dominant polycystic kidney disease was commenced on oral aciclovir 800 mg five times daily for suspected herpes simplex virus (HSV) stomatitis. This is a potentially toxic aciclovir dose for patients with ESRD. She was admitted 4 days later with confusion, expressive dysphasia, and visual hallucinations. She was apyrexial and denied headache. Neurological examination and neuro-imaging were normal. Her usual dialysis prescription of 3 h 15 min high-flux HD was changed to 4 h on-line HDF with a blood flow of 400 mL/min, a total dialysis flow rate of 800 mL/ min, and a convective clearance of 18 L using an FX800 dialyzer. The pre-HDF aciclovir level was 5.33 mmol/L. After 4 h of HDF, this was reduced by 83.3% to 0.89 mmol/L. The patient’s confusion resolved within 6 h post-HDF. Aciclovir is a small compound with a molecular weight of 225 daltons which is extensively renally cleared together with its metabolite, carboxymethoxymethylguanine (CMMG) (1). Serum aciclovir and CMMG levels increase markedly in renal impairment, predisposing such patients to aciclovir-induced neurotoxicity (1). Neuropsychiatric side-effects of aciclovir were first reported in the 1980s, and over 50 cases have since been described (1,2). The clinical syndrome is similar to HSV encephalitis and includes confusion, hallucinations and altered consciousness (1). In 2002, Bates reviewed 27 cases of reported aciclovir neurotoxicity and found a wide range of serum aciclovir levels (1.12–295 mmol/L), of which over 70% were less than 100 mmol/L (2). The plasma aciclovir levels reported here (5.33 mmol/L pre-HDF; 0.89 mmol/L post-HDF) support Bates’ suggestion that absolute serum aciclovir levels are not proportional to the risk of developing neurotoxicity. Nonetheless, HD—but not HDF—has been shown to lower plasma levels of aciclovir and CMMG, leading to marked improvements in neurotoxicity (1,3,4). An observational study of 83 patients by Helld en et al. reported a mean aciclovir reduction of 57 6 9% with 3–4 h standard HD (1). This is similar to the 51 6 11.5% reduction noted by Almond et al. (3). Our comparatively impressive 83.3% reduction may be related to the HDF therapy employed here. The FX800 dialyzer we used is also likely more efficacious than dialyzers used previously (1,3). Compared with HD, HDF improves clearance of small (<1.5 kD) and medium-sized (0.5–40 kD) molecules (5). Due to their similar molecular weights, HDF will likely also achieve more effective clearance of CMMG, although we have not measured this. This is significant given the suggestion that CMMG may be more important than aciclovir in the development of neurotoxicity (1). In summary, aciclovir should be dose-adjusted in patients with ESRD. This is the first published report documenting the effective treatment of aciclovir-induced neurotoxicity with HDF. We suggest HDF may be more effective than conventional HD in removing aciclovir, but further studies are warranted to define this more clearly and to clarify the extent of its effect on CMMG clearance.