Causes and prognostic value of pre-transplant elevated kynurenine level in kidney allograft recipients.
BACKGROUND
The activation of the tryptophane catabolizing enzyme Indoleamine 2,3-dioxygenase leads to the formation of kynurenine and other metabolites that counter-regulate immune activation resulting in restoration of immune homeostasis. But in chronic immune activation, as in hemodialysed patients, the immunosuppressive feedback mechanisms continue as indicated by elevated kynurenine concentrations. However, its relevance is still a matter of debate.


METHODS
This retrospective analysis presents the pre-transplant kynurenine levels (quantified photometrically) of 307 kidney graft recipients in connection with some pre- and post-transplant variables and the type of immunosuppression (cyclosporine-based triple drug therapy without/with ATG-Fresenius-induction). Statistical analyses performed were analysis of variance, Scheffé's test for pairwise comparisons, Cox regression, Spearman's rank correlation, and extended segmentation analysis.


RESULTS
The pre-transplant kynurenine level was significantly elevated as compared to healthy adults (14.1±5.9 vs. 2.7±0.6 nmol/ml, p<0.0001), significantly higher in PRA positive than in PRA negative patients (16.1 vs. 12.9 nmol/ml, p<0.001) and, supporting this observation, also higher (p<0.0001) in a cohort with predominant (89.7%) pre-sensitized patients (16.4±6.4 nmol/ml) having the longest time on the waiting list (median 39 months) as compared to cohorts with fewer (16.8-22%) pre-sensitized patients (12.7±4.4 resp. 13.4±5.8 nmol/ml) having shorter times on the waiting list (16-24 months). Patients with immediately functioning grafts showed a lower pre-transplant kynurenine level than patients with non-immediately functioning grafts (13.5±6.0 vs. 14.9±5.7 nmol/ml, p=0.053). No associations were found with basic diseases, rejections, or graft survival.


CONCLUSIONS
The pre-transplant elevated serum kynurenine levels were highly associated with the patient's pre-sensitization status and their longer time on hemodialysis treatments, but did not allow prognostic assessments.
Renal Transplant Centre, Berlin, Germany.
Jürgen
J
Kaden
University of Ulm, Centre of Surgery, Ulm, Germany.
Dietmar
D
Abendroth
Psy Consult Scientific Services, Frankfurt, Germany.
Andreas
A
Völp
Centre of Surgery, University of Ulm, Ulm, Germany.
Michael
M
Marzinzig
Renal Transplant Centre, Berlin, Germany.
Claus
C
Wesslau
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000276:immunology / Q000378:metabolism*; D016030:Kidney Transplantation; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D057234:Preoperative Period; D011379:Prognosis; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D055815:Young Adult
D007166:Immunosuppressive Agents; D007737:Kynurenine