Study of Indolamine 2,3-Dioxygenase in Kidney Allograft Recipients with Different Postoperative Courses

The activation of indolamine 2,3-dioxygenase (IDO), the main enzyme involved in the catabolism of tryptophan, generates immunosuppressive metabolites which counter-regulates immune activation. The interest of transplant immunologists to this control circuit rose sharply after it could be shown that IDO activity is of critical importance for immunologic acceptance of semiallogeneic fetuses in a mouse model. Experimental data leads to the hyothesis that regulatory T-cells exert their immunosuppressive function by initiation of IDO activity. This basic findings made the tryptophan metabolism also interesting for clinical transplantation. In a retrospective pilot study the L-kynurenine levels were determined in 379 sera from 40 recipients with well defined postoperative courses. The level of kynurenine reflects the degree of IDO activation. All recipients showed pre renal transplant significant elevated kynurenine levels (17,5 ± 5 nmol/ml; healthy people: 4,3 ± 1,5 ; organ donors: 6,5 ± 5,5). In recipients with immediately functioning renal grafts the kynurenine levels returned to normal within 3-5 days. Every delayed graft function was associated with elevated kynurenine levels, which also returned to normal after the beginning of graft function. In recipients with primarily functionless grafts the preoperatice elevated kynurenine levels did not change. In recipients with primarily functioning grafts a breakdown of graft function was promptly associated with a significant elevation of kynurenine level. These findings give evidence for the importance of IDO activity also in clinical renal transplantation. An extended study enrolling 156 recipients is drawing to a close and should finally clarify the clinical relevance of IDO activity.