Kynurenine Pathway after Kidney Transplantation: Friend or Foe?

Int J Mol Sci. 2024 Sep 14;25(18):9940. doi: 10.3390/ijms25189940.

Abstract

Kidney transplantation significantly improves the survival of patients with end-stage kidney disease (ESKD) compared to other forms of kidney replacement therapy. However, kidney transplant recipients' outcomes are not fully satisfactory due to increased risk of cardiovascular diseases, infections, and malignancies. Immune-related complications remain the biggest challenge in the management of kidney graft recipients. Despite the broad spectrum of immunosuppressive agents available and more detailed methods used to monitor their effectiveness, chronic allograft nephropathy remains the most common cause of kidney graft rejection. The kynurenine (KYN) pathway is the main route of tryptophan (Trp) degradation, resulting in the production of a plethora of substances with ambiguous properties. Conversion of Trp to KYN by the enzyme indoleamine 2,3-dioxygenase (IDO) is the rate-limiting step determining the formation of the next agents from the KYN pathway. IDO activity, as well as the production of subsequent metabolites of the pathway, is highly dependent on the balance between pro- and anti-inflammatory conditions. Moreover, KYN pathway products themselves possess immunomodulating properties, e.g., modify the activity of IDO and control other immune-related processes. KYN metabolites were widely studied in neurological disorders but recently gained the attention of researchers in the context of immune-mediated diseases. Evidence that this route of Trp degradation may represent a peripheral tolerogenic pathway with significant implications for transplantation further fueled this interest. Our review aimed to present recent knowledge about the role of the KYN pathway in the pathogenesis, diagnosis, monitoring, and treatment of kidney transplant recipients' complications.

Keywords: cancer; graft; immunosuppression; infection; kidney; kynurenic acid; kynurenine; rejection; transplantation; tryptophan.

Publication types

  • Review

MeSH terms

  • Animals
  • Graft Rejection / immunology
  • Graft Rejection / metabolism
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Indoleamine-Pyrrole 2,3,-Dioxygenase* / metabolism
  • Kidney Failure, Chronic / metabolism
  • Kidney Transplantation* / adverse effects
  • Kynurenine* / metabolism
  • Metabolic Networks and Pathways
  • Tryptophan / metabolism

Substances

  • Kynurenine
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Tryptophan
  • Immunosuppressive Agents