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. 2024 Sep 14;25(18):9940. doi: 10.3390/ijms25189940

Table 1.

Summary of KYN pathway activity alterations and their possible effects on kidney transplant recipients. ABMR, antibody-mediated rejection; CKD, chronic kidney disease; IDO, indoleamine-2,3,-dioxygenase; KMO, kynurenine 3-monooxygenase; KYN, kynurenine; KYNA, kynurenic acid; RCC, renal cell carcinoma; Tac, tacrolimus; TCR, T-cell-mediated rejection; Trp, tryptophan.

KYN Pathway Element Organ or System Function Modification
Indoleamine-2,3 dioxygenase (IDO)

  • High IDO activity correlates with chronic kidney disease (CKD) severity and inflammatory parameters [63];

  • IDO activity measurement as a tool for early CKD diagnosis [69];

  • IDO upregulation in tubular epithelial cells of rejected kidney grafts [102];

  • Higher IDO expression in kidney graft biopsies related to a higher incidence of antibody-mediated rejection (ABMR) or T-cell-mediated rejection (TCR) [105];

  • Elevated kynurenine (KYN)/tryptophan (Trp) ratio as a tool in differentiating acute graft rejection from infection [107,108];

  • High IDO expression in various cancers related to resistance to anticancer treatment and lower survival [133];

  • High IDO activity related to cardiovascular risk [23].
Kynurenine 3-monooxygenase (KMO)

  • Low KMO gene expression protein level [113] and activity [109] in a porcine model of kidney allograft rejection;

  • KMO knockout results in proteinuria in animal models [110];

  • Low podocytic KMO expression in diabetic patients [110];

  • Low KMO expression in renal cell carcinoma (RCC) patients [135];

  • KMO inhibitors as antineoplastic drugs in certain types of cancer [142].
Kynurenic acid (KYNA)

  • High serum KYNA level correlates with CKD severity and inflammatory markers [63];

  • High plasma KYNA levels correlate with procalcitonin and lactate concentration in survivors from septic shock, whereas a lack of KYNA concentration reduction relates to poor survival [126];

  • Plasma KYNA concentration correlates with hyperhomocysteinemia in peritoneal dialyzed patients with atherosclerotic cardiovascular disease [159];

  • Serum KYNA level related to aortic stiffness in patients with atrial fibrillation [160];

  • Tacrolimus Tac increases KYNA production [122].