Kynurenine pathway in kidney diseases

Pharmacol Rep. 2022 Feb;74(1):27-39. doi: 10.1007/s43440-021-00329-w. Epub 2021 Oct 6.

Abstract

Kidney diseases have become one of the most common health care problems. Due to a growing number of advanced aged patients with concomitant disorders the prevalence of these diseases will increase over the coming decades. Despite available laboratory tests, accurate and rapid diagnosis of renal dysfunction has yet to be realized, and prognosis is uncertain. Moreover, data on diagnostic and prognostic markers in kidney diseases are lacking. The kynurenine (KYN) pathway is one of the routes of tryptophan (Trp) degradation, with biologically active substances presenting ambiguous properties. The KYN pathway is known to be highly dependent on immunological system activity. As the kidneys are one of the main organs involved in the formation, degradation and excretion of Trp end products, pathologies involving the kidneys result in KYN pathway activity disturbances. This review aims to summarize changes in the KYN pathway observed in the most common kidney disease, chronic kidney disease (CKD), with a special focus on diabetic kidney disease, acute kidney injury (AKI), glomerulonephritis and kidney graft function monitoring. Additionally, the importance of KYN pathway activity in kidney cancer pathogenesis is discussed, as are available pharmacological agents affecting KYN pathway activity in the kidney. Despite limited clinical data, the KYN pathway appears to be a promising target in the diagnosis and prognosis of kidney diseases. Modulation of KYN pathway activity by pharmacological agents should be considered in the treatment of kidney diseases.

Keywords: Acute kidney injury; Chronic kidney disease; Kidney transplant; Kynurenic acid; Kynurenine; Tryptophan.

Publication types

  • Review

MeSH terms

  • Humans
  • Kidney Diseases* / diagnosis
  • Kidney Diseases* / drug therapy
  • Kidney Diseases* / metabolism
  • Kynurenine / metabolism*
  • Metabolic Networks and Pathways / drug effects
  • Metabolic Networks and Pathways / physiology

Substances

  • Kynurenine