title: Early Posttransplant Tryptophan Metabolism Predicts Long-term Outcome of Human Kidney Transplantation.
abstract: BACKGROUND
  Chronic transplant dysfunction (CTD) is the leading cause of long-term loss of the renal allograft. So far, no single test is available to reliably predict the risk for CTD. Monitoring of tryptophan (trp) metabolism through indoleamine 2.3-dioxygenase (IDO) has been previously proposed to predict acute rejection of human kidney transplants. Here, we investigate the potential of IDO/trp degradation along the kynurenine (kyn) pathway to predict the long-term outcome of human kidney transplantation.
  
  
  METHODS
  During the 2-year follow-up blood, urine, and kidney biopsies were collected from 48 renal transplant patients. Concentrations of kyn and trp in serum and urine were measured at 2 weeks, 6 months, and 2 years after transplantation. Kynurenine to tryptophan ratio was calculated as an estimate of trp degradation. To evaluate the histological changes and IDO expression, respectively, periodic acid schiff staining and immunohistochemistry for IDO were performed on biopsies taken at 6 months and 2 years.
  
  
  RESULTS
  Two years after transplantation, kyn/trp was increased in urine and decreased in serum as compared to 2-week values. In 2-year biopsies, IDO expression was mainly found in infiltrating inflammatory cells and in the glomeruli. The urine level of trp 2 weeks after transplantation predicted the serum creatinine 6 months and the estimated creatinine clearance 2 years after transplantation. Additionally, serum level of kyn 6 months after transplantation predicted the serum creatinine 2 years after transplantation.
  
  
  CONCLUSIONS
  Early serum and urine levels of trp and kyn may offer a novel route for early detection of patients at risk for developing CTD.
authors: 1 Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, the Netherlands. 2 Graduate School for Drug Exploration (GUIDE), University of Groningen, University Medical Center Groningen, the Netherlands. 3 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia. 4 Department of Internal Medicine, University of Groningen, University Medical Center Groningen, the Netherlands. 5 Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. 6 Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, the Netherlands. 7 Ludwig Institute for Cancer Research, Brussels, Belgium. 8 de Duve Institute, Université Catholique de Louvain, Brussels, Belgium. 9 Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors: Diana
authors: D
authors: Vavrincova-Yaghi
authors: Marc A
authors: MA
authors: Seelen
authors: Ido P
authors: IP
authors: Kema
authors: Leo E
authors: LE
authors: Deelman
authors: Marius C
authors: MC
authors: van der Heuvel
authors: Henk
authors: H
authors: Breukelman
authors: Benoit J
authors: BJ
authors: Van den Eynde
authors: Rob H
authors: RH
authors: Henning
authors: Harry
authors: H
authors: van Goor
authors: Maria
authors: M
authors: Sandovici
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000652:urine; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D007677:Kidney Function Tests / Q000379:methods*; D016030:Kidney Transplantation / Q000009:adverse effects*; D007737:Kynurenine / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014364:Tryptophan / Q000097:blood* / Q000652:urine*
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan; D003404:Creatinine