Novel risk factor for valganciclovir toxicity—NUDT15 genetic variant

Abstract

Recent "in vitro" studies describe nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) enzyme to be involved in the metabolism of ganciclovir. 1,2 We report severe leukopenia during therapy with valganciclovir in a recent kidney transplant recipient with NUDT15 genetic variation. This case report is the first to substantiate a theoretical postulate of increased valganciclovir toxicity with NUDT15 variation.

PharmGKB summary: acyclovir/ganciclovir pathway

“…Low NUDT15 activity in CMV-positive donor cells was associated with an increased rate of graft failure ( P = 0.047), suggesting a protective role for NUDT15 against ACV and GCV cytotoxicity. Recently, an NUDT15 -linked severe neutropenia was reported in an Indian patient who received azathioprine (100 mg/day) and VGCV (450 mg/day) as CMV prophylaxis after a kidney transplant [84]. Genotyping revealed the patient to be a normal metabolizer for TPMT (thiomethylpurine transferase), the main enzyme that catabolizes azathioprine, but the carrier of two copies of the *3 allele of NUDT15 .…”