Association of phenylalanine and tryptophan metabolites with activated cytomegalovirus infection in kidney transplant recipients

Imad Lhadou¹, Mahmoud Sadeghi¹, Volker Daniel¹, Paul Schnitzler², Gerhard Fusch³, Joerg C. Schefold⁴, Martin Zeier⁵, Gerhard Opelz¹, Peter Terness¹.

Departments of ¹Transplantation Immunology and ²Infectious Diseases - Virology, University of Heidelberg, Heidelberg; ³Department of Paediatrics, University of Greifswald, Greifswald; ⁴Department of Nephrology and Intensive Care, Charité University Medicine, Berlin; ⁵Department of Nephrology, University of Heidelberg, Heidelberg; Germany.

Infection-induced inflammation triggers catabolism of proteins and amino acids. Phenylalanine and tryptophan metabolites are related to infections and regulate immune responses. Polyomavirus BK (BKV) and cytomegalovirus (CMV) are important pathogens after kidney transplantation. We investigated the clinical relevance of phenylalanine, tryptophan, tryptophan metabolites (kynurenine, quinolinic acid) plasma levels, and kynurenine/tryptophan as well as quinolinic acid/tryptophan ratios in kidney transplant recipients with active CMV (CMV+BKV-: n=12) or BK virus infection (BKV+CMV-: n=37). Recipients without active infections (CMV-BKV-: n=28) and CMV-BKV- healthy individuals (HCs: n=50) served as controls. In contrast to BKV infection, activated CMV infection is tightly linked to increased phenylalanine and tryptophan metabolite plasma levels in kidney allograft recipients (p£0.002). The association of phenylalanine (cut-off: 50 µmol/L) with CMV infection showed very high sensitivity (100%) and specificity (94%). Kynurenine (p=0.029) and quinolinic acid (p=0.003) values reflect the severity of CMV infection. Our findings have practical relevance for the rapid differentiation of CMV from BKV infections, evaluation of infection severity, monitoring of therapy, and development of novel therapeutic approaches.