Please use this identifier to cite or link to this item: https://doi.org/10.1159/000519811
Title: The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease
Authors: Wee. H.N. 
Liu J.-J.
Ching J.
Kovalik J.,-P. 
Lim S.C. 
Keywords: Kynurenine; Tryptophan; Acute kidney injury; Chronic kidney disease; Uremia; Inflammation
Issue Date: 9-Nov-2021
Publisher: S. Karger AG
Citation: Wee. H.N., Liu J.-J., Ching J., Kovalik J.,-P., Lim S.C. (2021-11-09). The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease. American Journal of Nephrology 52 (10-11). ScholarBank@NUS Repository. https://doi.org/10.1159/000519811
Rights: Attribution-NonCommercial 4.0 International
Abstract: Background: The kynurenine pathway (KP) is the major catabolic pathway for tryptophan degradation. The KP plays an important role as the sole de novo nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway in normal human physiology and functions as a counter-regulatory mechanism to mitigate immune responses during inflammation. Although the KP has been implicated in a variety of disorders including Huntington’s disease, seizures, cardiovascular disease, and osteoporosis, its role in renal diseases is seldom discussed. Summary: This review summarizes the roles of the KP and its metabolites in acute kidney injury (AKI) and chronic kidney disease (CKD) based on current literature evidence. Metabolomics studies demonstrated that the KP metabolites were significantly altered in patients and animal models with AKI or CKD. The diagnostic and prognostic values of the KP metabolites in AKI and CKD were highlighted in cross-sectional and longitudinal human observational studies. The biological impact of the KP on the pathophysiology of AKI and CKD has been studied in experimental models of different etiologies. In particular, the activation of the KP was found to confer protection in animal models of glomerulonephritis, and its immunomodulatory mechanism may involve the regulation of T cell subsets such as Th17 and regulatory T cells. Manipulation of the KP to increase NAD+ production or diversion toward specific KP metabolites was also found to be beneficial in animal models of AKI. Key Messages: KP metabolites are reported to be dysregulated in human observational and animal experimental studies of AKI and CKD. In AKI, the magnitude and direction of changes in the KP depend on the etiology of the damage. In CKD, KP metabolites are altered with the onset and progression of CKD all the way to advanced stages of the disease, including uremia and its related vascular complications. The activation of the KP and diversion to specific sub-branches are currently being explored as therapeutic strategies in these diseases, especially with regards to the immunomodulatory effects of certain KP metabolites. Further elucidation of the KP may hold promise for the development of biomarkers and targeted therapies for these kidney diseases.
Source Title: American Journal of Nephrology
URI: https://scholarbank.nus.edu.sg/handle/10635/214276
ISSN: 0250-8095
1421-9670
DOI: 10.1159/000519811
Rights: Attribution-NonCommercial 4.0 International
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
AJN519811.pdf805.69 kBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

7
checked on Nov 25, 2022

Page view(s)

74
checked on Nov 17, 2022

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons