Kynurenines in polycystic kidney disease
Jost Klawitter1, Matthew J Jackson1, Peter H Smith1
1Department of Anesthesiology, University of Colorado School of Medicine, University of Colorado Denver Anschutz Medical Campus, 12705 E Montview Blvd, Bioscience 2, Suite 200, Aurora, CO, 80045-7109, USA.
Journal of Nephrology
|July 22, 2022
Summary
Tryptophan metabolism is altered in Autosomal dominant polycystic kidney disease (ADPKD), with elevated kynurenines linked to disease severity. Targeting kynurenine production may offer a new therapeutic approach for ADPKD.
Area of Science:
- Nephrology
- Metabolic pathways
- Inflammation research
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by kidney cyst development and interstitial inflammation.
- Tryptophan metabolism and its byproducts, kynurenines, are implicated in inflammatory and oxidative stress pathways, suggesting a potential role in ADPKD pathogenesis.
Purpose of the Study:
- To investigate the association of kynurenines with disease severity and progression in pediatric and adult ADPKD patients.
- To compare kynurenine levels in ADPKD patients with age-matched healthy controls.
Main Methods:
- Collected data from a longitudinal cohort of ADPKD patients and healthy controls.
- Measured key tryptophan metabolites in plasma using liquid chromatography-mass spectrometry.
- Assessed associations between kynurenines, height-corrected total kidney volume (HtTKV), and estimated glomerular filtration rate (eGFR).
Main Results:
- Significant accumulation of kynurenine and kynurenic acid (KYNA) observed in ADPKD patients compared to controls.
- Downstream kynurenines and inflammatory markers (IL-6, MCP-1) increased in adult ADPKD patients.
- KYNA and kynurenine/tryptophan ratio positively correlated with ADPKD severity (HtTKV and eGFR).
Conclusions:
- Kynurenine metabolism is dysregulated in ADPKD.
- Inhibiting kynurenine production may represent a novel therapeutic strategy to slow ADPKD progression.
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