Adverse neuropsychiatric effects of cytomegalovirus prophylaxis with valaciclovir in renal transplant recipients.
BACKGROUND
Valaciclovir (VACV) has been reported to induce adverse neuropsychiatric effects (ANE), especially in patients with renal failure, but few data are available for renal transplant recipients (RTR).


METHODS
We conducted a retrospective study in RTR given VACV as cytomegalovirus prophylaxis, from January 1999 to December 2000, to define the incidence rate, type and outcome of VACV-induced ANE, and to identify risk factors for ANE. The VACV-induced ANE were defined as neuropsychiatric disorders justifying VACV dose reduction or withdrawal. Patients with and without VACV-induced ANE were compared by univariate and multivariate analysis.


RESULTS
In all, 167 RTR were included, of whom 25 (15%) displayed VACV-induced ANE (mainly hallucinations and confusion), which occurred with a mean of 4 days after the start of VACV. ANE were reversible in all cases. Multivariate analysis showed that delayed graft function (DGF) was the main risk factor for VACV-induced ANE [Odds ratio (OR): 12.1; 95% CI = 3.4-43.4; P = 0.0001]. All VACV doses given to patients with ANE were in accordance with the current recommended adaptation to estimated glomerular filtration rate (GFR).


CONCLUSIONS
In RTR, VACV-induced ANE are significantly frequent but reversible. DGF occurrence is the main risk factor for these ANE. In RTR with DGF, the recommended doses for GFR below 10 ml/min might be too high. Several strategies, in RTR with DGF, might lower the risk of ANE, including reduction of the currently recommended VACV dosage, delayed VACV introduction until improvement of renal function, or use of another anti-cytomegalovirus drug.
Das
Vincent
V
Service de Transplantation Rénale, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France.
Peraldi
Marie-Noelle
MN
Legendre
Christophe
C
D000212:Acyclovir / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D017677:Age Distribution; D000704:Analysis of Variance; D001526:Behavioral Symptoms / Q000139:chemically induced* / Q000453:epidemiology* / Q000503:physiopathology; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005602:France / Q000453:epidemiology; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011336:Probability; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D017678:Sex Distribution; D000077483:Valacyclovir; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir