Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1097/TP.0000000000000603

Type

Journal article

Journal

Transplantation

Publication Date

08/2015

Volume

99

Pages

e97 - 104

Keywords

Biomarkers, Biopsy, Creatinine, Early Diagnosis, Female, Humans, Immunohistochemistry, Immunosuppressive Agents, Indoleamine-Pyrrole 2,3,-Dioxygenase, Kidney, Kidney Diseases, Kidney Function Tests, Kidney Transplantation, Kynurenine, Male, Middle Aged, Predictive Value of Tests, Prospective Studies, Time Factors, Treatment Outcome, Tryptophan