Kidney cyst development is a common inherited illness known as autosomal dominant polycystic kidney disease (ADPKD). Interstitial inflammation development is a key pathogenic aspect of ADPKD. The metabolism of tryptophan and associated kynurenines may be important in ADPKD due to its function in oxidative stress and inflammation.
Data were gathered from a longitudinal cohort of pediatric and adult ADPKD patients that had been well-characterized, and they were compared to age-matched healthy volunteers. For a study, researchers determined the relationship between kynurenines and kidney function, including estimated glomerular filtration rate (eGFR), height-corrected total kidney volume (HtTKV), and ADPKD severity and progression. A validated liquid chromatography-mass spectrometry technique was used to quantify important tryptophan metabolites in plasma.
In comparison to healthy participants, there was a considerable increase in kynurenine and kynurenic acid (KYNA) in children and adults with ADPKD. Adults with ADPKD continued to accumulate downstream kynurenines at the same time that IL-6 and MCP-1 levels rose. When compared to children without ADPKD, both markers remained stable, indicating that other mechanisms may have contributed to the elevation in kynurenine and KYNA that was seen. In patients with ADPKD, the levels of KYNA and kynurenine/tryptophan were strongly correlated with disease severity (HtTKV or eGFR). In the small group of ADPKD patients, baseline kynurenines did not correlate with disease progression (annual percent change in HtTKV or annual change in eGFR) after Bonferroni correction.
When compared to healthy patients, the metabolism of kynurenine in ADPKD appears to be dysregulated. A potential strategy to slow the course of ADPKD may involve inhibiting the major pathway enzymes, which inhibit the formation of kynurenine.