Delayed graft function and rejection are risk factors for cytomegalovirus breakthrough infection in kidney transplant recipients

Wieteke Kleinherenbrink*, Marije Baas, Gizal Nakhsbandi, Dennis A. Hesselink, Joke I. Roodnat, Brenda C. de Winter, Luuk Hilbrands, Teun van Gelder

*Corresponding author for this work

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Breakthrough cytomegalovirus (CMV) disease during valganciclovir prophylaxis is rare but may cause significant morbidity and even mortality. In order to identify patients at increased risk the incidence of CMV disease was studied in a large population of renal transplant recipients who underwent a kidney transplantation in the Radboud University Medical Center between 2004 and 2015 (n = 1300). CMV disease occurred in 31/1300 patients. Multivariate binary linear regression analysis showed that delayed graft function (DGF) (p = 0.018) and rejection (p = 0.001) significantly and independently increased the risk of CMV disease, whereas CMV status did not. Valganciclovir prophylaxis was prescribed to 281/1300 (21.6%) high-risk patients (defined as CMV IgG-seronegative recipients receiving a kidney from a CMV IgG-seropositive donor (D+/R-)). Of these 281 patients, 51 suffered from DGF (18%). The incidence of breakthrough CMV disease in D + /R- patients with DGF was much higher than in those with immediate function (6/51 (11.8%) vs 2/230, (0.9%), p = 0.0006 Fisher's exact test), despite valganciclovir prophylaxis. This higher incidence of CMV disease could not be explained by a higher incidence of rejection (and associated anti-rejection treatment) in patients with DGF. D + /R- patients with DGF are at increased risk of developing CMV disease despite valganciclovir prophylaxis. These findings suggest that underexposure to ganciclovir occurs in patients with DGF. Prospective studies evaluating the added value of therapeutic drug monitoring to achieve target ganciclovir concentrations in patients with DGF are needed.

Original languageEnglish
Article number105565
JournalPharmacological Research
Early online date31 Mar 2021
Publication statusPublished - May 2021

Bibliographical note

Funding Information:
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: WK reports no conflicts of interest. TvG has received lecture fees from Chiesi and Astellas Pharma, and consulting fees from Roche Diagnostics, Aurinia, Vitaeris, Astellas and Novartis. LH has received consulting fees from Chiesi and Novartis. DAH has received lecture and consulting fees from Astellas Pharma and Chiesi, as well as grant support from Astellas Pharma, Bristol Myers-Squibb and Chiesi. MB reports no conflicts of interest.

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© 2021


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