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Increased pretransplantation plasma kynurenine levels do not protect from but predict acute kidney allograft rejection

Indoleamine 2,3-dioxygenase (IDO), an enzyme expressed in many cell types, catalyses degradation of tryptophan (Trp) to kynurenine (Kyn) and may exert immunosuppressive functions, mediated mainly by kynurenines. Therefore, increased Kyn concentrations would be expected to protect allografts from rej...

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Main Authors: Lahdou, Imad (Author) , Sadeghi, Mahmoud (Author) , Daniel, Volker (Author) , Schenk, Martin (Author) , Renner, Fabrice (Author) , Weimer, Rolf (Author) , Löb, Stefan (Author) , Schmidt, Jan (Author) , Mehrabi, Arianeb (Author) , Schnitzler, Paul (Author) , Königsrainer, Alfred (Author) , Döhler, Bernd (Author) , Opelz, Gerhard (Author) , Terness, Peter (Author)
Format: Article (Journal)
Language:English
Published: 21 August 2010
In: Human immunology
Year: 2010, Volume: 71, Issue: 11, Pages: 1067-1072
ISSN:1879-1166
DOI:10.1016/j.humimm.2010.08.013
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.humimm.2010.08.013
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0198885910004817
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Author Notes:Imad Lahdou, Mahmoud Sadeghi, Volker Daniel, Martin Schenk, Fabrice Renner, Rolf Weimer, Stefan Löb, Jan Schmidt, Arianeb Mehrabi, Paul Schnitzler, Alfred Königsrainer, Bernd Döhler, Gerhard Opelz, Peter Terness
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Summary:Indoleamine 2,3-dioxygenase (IDO), an enzyme expressed in many cell types, catalyses degradation of tryptophan (Trp) to kynurenine (Kyn) and may exert immunosuppressive functions, mediated mainly by kynurenines. Therefore, increased Kyn concentrations would be expected to protect allografts from rejection. We conducted this study to examine whether Kyn has predictive value for kidney graft outcome. End-stage renal disease patients (n = 210) demonstrated an increased Kyn/Trp ratio compared with healthy controls (n = 30). Both Kyn and Trp levels were significantly higher in patients who subsequently developed acute rejection than in patients who did not (p < 0.001 and p < 0.001, respectively). Furthermore, pretransplantation Kyn and Trp plasma concentrations were significantly different in patients who went on to develop acute rejection (high values) or acute tubular necrosis (low values) (p = 0.007 and p = 0.021, respectively). After transplantation Kyn levels decreased. Approximately 3 days before biopsy-confirmed rejection, Kyn was significantly increased in patients with rejection compared with those without rejection (p < 0.001). Contrary to expectation, high Kyn plasma levels before transplantation were not predictive of low rejection risk. Although informative in overall terms, at the present stage, Kyn levels do not allow the concise risk differentiation of individual patients.
Item Description:Gesehen am 09.03.2023
Physical Description:Online Resource
ISSN:1879-1166
DOI:10.1016/j.humimm.2010.08.013

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