The renal safety of high doses of valacyclovir for prevention of cytomegalovirus infection after renal transplantation

Valacyclovir is a prodrug which increases oral acyclovir bioavailability 3-5-fold.When high dosages (6-8 g/day) are used, oral intake of valacyclovir achieves plasma concentrations (area under the curve: AUC ) comparable with those of intravenous (i.v.) acyclovir 10 mg/kg three times daily [3].It is well known that i.v.acyclovir can cause crystal formation in renal tubules that can lead to acute renal failure [4][5].About one third of patients experienced a transient increase in the serum creatinine level during i.v.acyclovir therapy [4].This acyclovir-induced nephrotoxicity is potentiated by cyclosporin [6 ].The appearance of acyclovir crystalluria is considered to be a warning sign which precedes the rise of the serum creatinine level [7].We investigated the frequency of crystalluria and the renal drug safety in kidney transplant recipients treated with cyclosporin in whom oral valacyclovir was used for the prevention of CMV disease.Six patients were enrolled in the study.All were CMV-seronegative patients transplanted with a graft from a CMV-seropositive donor.The immunowith chronic renal failure undergoing radiocontrast studies suppressive regimen was quadruple and sequential consisting was lower in the saline only pretreatment group (11%).The of antithymocyte globulin for 6-8 days, associated with incidence of the saline and mannitol group and saline plus mycophenolate mofetil and corticosteroids.Cyclosporin A furosemide pretreatment group was 28% and 40%, respectwas introduced 2 days before the antithymocyte globulin ively.When extrapolating the data presented in the paper, I was discontinued.come up with numbers for NNT as shown in Table 1.ThisValacyclovir was started on the 3-7 day after transplantadata can be interpreted as follows: in patients with chronic tion at the dosage of 6 g/day if the creatinine clearance renal failure undergoing radiographic procedure, pretreatexceeded 50 ml/min or 4.5 g/day if the clearance was between ment with saline alone, when compared to saline and furose-25 and 50 ml, and continued for 3 months.Because all mide therapy, results in an absolute risk reduction of 29%, patients had good renal function they were treated with 6 g leading to a NNT of 3. Stated in a different way: pretreatment of valacyclovir after 2 weeks of transplantation.Serum creatinine concentrations did not increase during treatment.of 100 chronic renal failure patients undergoing an angiogram Granulocytes were analysed weekly for CMV antigen.with saline alone, rather than pretreatment with saline and During the first 3 months of valacyclovir treatment, the furosemide, results in 33 fewer incidents of contrast-induced granulocyte test became positive in only one of the six renal function deterioration.The NNT for saline and mannipatients, and this patient remained asymptomatic.tol group was 8.This is of clinical importance to the A search for urinary crystals was performed on fresh urine nephrologist in being able to objectively quantify the imporsamples two times per week during the first month and once tance of the study and explain the results of a new therapy per week over the next 2 months using polarization microto other physicians.Routine presentation of statistical as scopy.Acyclovir crystalluria was never detected in the six well as clinical significance of clinical data could greatly patients at any time during the 3 months of treatment.enhance the applicability of a study.We conclude that valacyclovir is effective and safe in the University of Minnesota Amit K. Ghosh prevention of CMV disease in renal allograft recipients.The Minneapolis pharmacokinetic properties of this drug which has an AUC Minnesota similar to that of i.v.acyclovir without a serum peak could USA account for the absence of crystalluria and deterioration of renal function.However, our preliminary findings, especially