Background Tacrolimus (Tac) is the cornerstone of immunosuppressive therapy in kidney transplant recipients. It is metabolized by members of the cytochrome p450 (CYP) 3A subfamily mainly CYP 3A5. In experimental models, CYP enzymes were shown to be altered during sepsis.

We have observed that some patients admitted for severe infection presented with increased trough levels (TL) of Tac requiring dose adjustment. We hypothesized that infection induces a hepatocyte dysfunction leading to alteration of Tac metabolization.

Methods Retrospective study on patients transplanted with a kidney between January 2009 and December 2011, who were hospitalized for infection. Increased levels of Tac were defined as TL upon admission for infection 25% higher than TL recorded at last visit.

Results 77 patients were hospitalized for 138 episodes of infection. Their median age at transplantation was 53 (19-73) years. At the time of hospitalization, immunosuppressive regimen comprised Tac for all patients, mycophenolate mofetil for 88%, azathioprine for 1 % and corticosteroids for 97% of patients. Analysis of infections revealed that the most frequent type of infection was urinary (33%), followed by cytomegalovirus (infection 22%; disease 5%), digestive (15%), pulmonary (12%), systemic (6%), and cutaneaous (4%) disease. Infectious agents were mostly bacterial (45%) (E.coli accounting for 22%).

Thirty-four hospitalization occuring in 27 patients were characterized by increased Tac TL upon admission. Comparing these hospitalisations with the 104 others, we found a statistically significant difference in the cause of infection related to digestive etiologies. The occurrence of diarrhea was not significantly different between the 2 groups. We did not find any difference in age at transplantation, sex, immunosuppressive regimen, initial nephropathy, CYP3A5 and ABCB1 genotype, previous history of hepatitis B or C, CRP and MDRD.

Conclusion A non-negligible number of patients present with an increased Tac TL upon admission for infection requiring hospitalisation. The risk factor identified is a digestive cause for infection, unrelated to the occurrence of diarrhea.

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